Dr. Thomas P. Monath, a physician, is a consultant to the biotechnology industry. He is currently Chief Scientific and Chief Operations Officer of [NewLink Genetics Corporation]’s wholly-owned subsidiary, BioProtection Systems Corp. and is helping determine if the Canadian/NewLink Ebola vaccine candidate will provide part of the solution to one of the world’s biggest public health challenges. He was formerly Chief Medical Officer of Hookipa BioTech AG and Chief Technical Officer of PaxVax Inc, where he was also engaged in development of new vaccines. His expertise and experience cut across discovery research, process and analytical development, manufacturing, preclinical and clinical development, and regulatory affairs. Monath is also a Venture Partner at Kleiner Perkins Caufield & Byers and is a Director of Sentinext plc, Rapid MicroBiosystems Inc, and U.S. Biologics Inc.

Between1992-2012 he was Adjunct Professor, Harvard School of Public Health. Between 1992 and 2006. Dr. Monath was Chief Scientific Officer and an Executive Director, Acambis plc (a publicly traded biopharmaceutical company recently acquired by Sanofi Pasteur) where he pioneered the development of ChimeriVax® vaccines against dengue, West Nile, and Japanese encephalitis (using yellow fever as a live vector), vaccines against yellow fever, Clostridium difficile, and Helicobacter pylori, as well as a cell based smallpox vaccine, ACAM2000 which has now replaced calf lymph vaccine in the US national stockpile. The JE vaccine (IMOJEV®) is licensed in multiple countries; the West Nile vaccine (Prevenile®) is licensed for use in horses; and the dengue and C. difficile vaccines are in Phase III trials.

Dr. Monath received his undergraduate and M.D. degrees from Harvard and trained in internal medicine at the Peter Bent Brigham Hospital, Boston. COL Monath retired from the US Army in 1992 after 24 years in the uniformed services (Army and U.S. Public Health Service). Between 1973-1988, he was Director, Division of Vector-Borne Viral Diseases, U. S. Centers for Disease Control (CDC), Fort Collins CO and from 1989-92 Chief, Virology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). He has worked overseas in Nigeria, Sierra Leone, Cameroun, Argentina, Ecuador and elsewhere doing field research on arboviruses and hemorrhagic fevers. In 1972, he discovered the rodent reservoir of Lassa fever virus. He is on the editorial board of 5 scientific journals.

He received the Nathanial A. Young Award (1984), the Richard M. Taylor Award (1996), and the Walter Reed Medal (2002) from the American Society of Tropical Medicine & Hygiene and was President of that Society (2004-05). He has served on numerous government and international committees on infectious diseases, biosecurity, World Health Organization expert committees and the National Vaccines Advisory Committee (USA). From 1998-2000, Monath was Senior Science advisor to the Director, Central Intelligence Agency. Dr. Monath has published 400 papers and 6 books on the epidemiology, immunology and pathogenesis of arboviruses and on vaccine development.

A leader in the “One Health” movement, Dr. Monath served on the American Veterinary Medical Association’s “One Health” Task Force and subsequently the One Health Commission (USA). He currently co-manages the One Health Initiative website http://www.onehealthinitiative.com with Laura H. Kahn, MD, MPH, MPP, Bruce Kaplan, DVM, Jack Woodall, PhD and Lisa A. Conti, DVM, MPH. Dr. Monath co-edited a unique ‘first of its kind’ One Health monograph in the Veterinaria Italiana Journal’s 2009 - Volume 45 (1), January-March http://www.izs.it/vet_italiana/2009/45_1/45_1.htm with Drs. Kahn and Kaplan. They also co-authored the introductory chapter to the 2010 One Health book “Human-Animal Medicine – Clinical Approaches to Zoonoses, Toxicants and other Shared Health Risks” http://www.us.elsevierhealth.com/product.jsp?isbn=9781416068372 and co-edited the 2014 One Health book “Confronting Emerging Zoonoses – The One Health Paradigm” http://www.springer.com/978-4-431-55119-5 with Akio Yamada, DVM, PhD and the One Health Initiative team.  

Here's what I found: 

Executive Profile 

Thomas P. Monath M.D. 

Chief Scientific Officer and Chief Operations Officer of Infectious Disease Division, NewLink Genetics Corporation 

Age Total Calculated Compensation This person is connected to 4 Board Members in 4 different organizations across 16 different industries. 

See Board Relationships 

75 -- 

Background 

"He serves as an Advisor of Metabiota, Inc. " ... 

Dr. Thomas P. Monath, also known as Tom, M.D., has been the Chief Scientific and Chief Operations Officer at BioProtection Systems Corporation since November 2014. Dr. Monath serves as Chief Operations Officer of Infectious Disease Division and Chief Scientific Officer of NewLink Genetics Corporation. He joined NewLink Genetics in 2014. He serves as an Advisor of Metabiota, Inc. He serves as the Chief Medical Officer of HX Diagnostics, Inc. He served as Consulting Chief Medical Officer of Mymetics Corporation since August 2012. He served as a Director, Division of Vector-Borne Viral Diseases at U.S. Centers For Disease Control And Prevention (cdc). He served as a Venture Partner and Partner at KPCB Pandemic and Bio Defense Fund at Kleiner Perkins Caufield & Byers. Dr. Monath has devoted his nearly 30-year career to the fight against infectious disease through his work in the military, corporate, academic and investment sectors. He was a Venture Partner and Partner at Kleiner, Perkins, Caufield & Byers. He served as the Chief Technology Officer of PaxVax Corporation since February 2012. He served as the Chief of the Virology Division at U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). Dr. Monath was an Investment Partner at USAMRIID. He served as the Chief Scientific Officer and Executive Director at Sanofi Pasteur Holding Limited (Acambis Plc) from 1992 to 2006, where Dr. Monath directed research and development on dengue, West Nile, Japanese encephalitis, yellow fever, Clostridium difficile and smallpox vaccines for defense against bioterrorism. He served as Acting Chief Medical Officer of Juvaris BioTherapeutics Inc. He served as Vice President of Research and Medical Affairs at Sanofi Pasteur Biologics Co. since December 1993. Dr. Monath served as a Vice President of Research and Development at Oravax Inc from April 1992 to December 1993. He served as Consultant at Oravax Inc. from October 1991 to March 1992. He served as Director of Division of Vector-Borne Viral Diseases at U.S. Centers for Disease Control, Fort Collins CO, from 1973 and 1988. He served as the Chief of Virology Division in United States Medical Research Institute of Infectious Diseases from 1989 to 1992. Dr. Monath joined Kleiner, Perkins, Caufield & Byers in June 26, 2006 and is a part of the life sciences team and specializes in pandemic and Biodefence investments. He retired from the United States army in 1992 after 24 years in the uniformed services. He served as Executive Director at Sanofi Pasteur Holding Limited (Acambis Plc )from 1992 to 2006. He has been a Director of Rapid Micro Biosystems, Inc. since July 2009. He served as a Director of Juvaris BioTherapeutics, Inc. since January 5, 2007 and VaxInnate Corporation since June 2015. He serves as a Member of Advisory Board of SmartVet USA Inc. He is a Member of Scientific Advisory Board at SutroVax, Inc. He serves as a Director of Acambis Plc. He served as a Director of Xcellerex, Inc. He served as a Director of Novavax Inc. from September 2006 to November 2, 2009. He served as a Member of Medical Advisory Board at Symphogen A/S. Dr. Monath is a world-renowned virologist and vaccinologist with over 25 years of experience as a senior biotechnology industry executive, more than 20 years of experience providing service to the Centers for Disease Control and the United States Army with expertise in viral infections and almost 400 publications in the field. Dr. Monath has successfully developed and provided clinical trial oversight of multiple vaccines and has extensive experience and success working with the US Food and Drug Administration. He is on the editorial board of five scientific journals. Dr. Monath received the Nathanial A. Young Award in 1984, the Richard M. Taylor Award in 1996 and the Walter Reed Medal in 2002 from the American Society of Tropical Medicine & Hygiene and was President of that Society from 2004 to 2005. He is an Adjunct Professor at the Harvard School of Public Health. He has published over 40 patents on various products, 380 papers and edited six books on the epidemiology, immunology and pathogenesis of viruses and on vaccine development. In 1992, he retired as a U.S. Army colonel following 24 years in the uniformed services. He trained in Internal Medicine at the Peter Bent Brigham Hospital, Boston. Dr. Monath received an M.D. from Harvard Medical School and a B.A. from Harvard College.

On May 22, President Clinton unveiled an ambitious plan to stockpile vaccines at strategic sites around the country so communities could better fight germ attacks. ''We must do more to protect our civilian population,'' Mr. Clinton told graduating midshipmen at the United States Naval Academy in Annapolis, Md. ''We must do more to protect our people.''

While such major initiatives usually result from many months and sometimes years of fierce debate, this one, Federal and private experts said in interviews, was developed in record time, rushed through amid worries of rising threats from Iraq and germ terrorists. But today the multimillion-dollar plan is in jeopardy, a victim in part of the haste in which the decision was reached.

Some Government officials are calling for a different approach that initially plays down vaccines in favor of antibiotics. Others defend vaccines, but concede that getting them quickly is nearly impossible, given industry's production limits and the need to insure vaccine safety and effectiveness. Still others fault vaccines as offering little or no protection against such deadly threats as smallpox and anthrax, seen as likely weapons in germ attacks.

A review of events leading to the Clinton vaccine decision reveals that the proposal was pushed by a small group of scientists, businessmen and policy makers who largely shared the same views as they struggled to do something, anything about a threat whose dimensions were potentially terrifying but frustratingly unclear. Working in Washington's frenetic, often insular world, they tended to overwhelm or sidestep doubters, and failed to see warning signs.

*The apparent consensus on acquiring vaccines masked deep divisions among scientists and military officials.

[Dr. William Capers Patrick III (born 1926)], who made germ weapons for the United States before President Richard M. Nixon outlawed them nearly three decades ago, warned that vaccinations against particular germs could be easily countered by foes, making such safeguards potentially useless.

''It's a hell of a problem,'' Mr. Patrick said. ''Defensive measures are much more difficult than offensive ones. There's no easy way around it. You immunize against anthrax and then an enemy just tries something else.''

Even the Administration's top public health officials have begun to warn that stockpiling is no quick fix.

''My view is that the stockpile isn't sufficient,'' said a senior Administration official, who spoke on condition of anonymity. ''We need an entire care system in place'' to avoid creating a false sense of security.

And Congress, which has strongly supported the Administration's anti-terrorism efforts, is questioning the rationale and structure of the civilian stockpile. A Senate hearing is being considered for the fall.

''The plan,'' said Senator Lauch Faircloth, Republican of North Carolina, ''needs to be more carefully thought out and discussed more publicly.''

The Pentagon -  In Early Debate, Focus on Troops

For decades, scientists and military officials debated the merits of vaccines as a defense against germ warfare. Worries grew after the 1991 Persian Gulf war, when United Nations inspectors found that President Saddam Hussein of Iraq had studied dozens of microbial agents and had placed at least 180 biological bombs and warheads around his country ready to spray lethal germs on enemy troops.

As the Pentagon discussed an ambitious program to make a variety of vaccines, its officials weighed the possibility that enemies would simply choose new deadly germs or modify old ones to outwit American defenses.

''People asked if we were just making it possible for Saddam to pick another agent,'' recalled Stephen C. Joseph, a doctor who at the time was Assistant Secretary of Defense for health affairs.

Dr. Joseph added that he and his Pentagon colleagues nonetheless recommended in the mid-1990's that the military embark on a vaccine effort. They were motivated in part, Pentagon officials said, by intelligence reports of rising dangers outside Iraq of germs being used against American troops.

In 1996, the Pentagon began looking for a company to develop and obtain licenses for 18 vaccines other than the standard one for anthrax. The initial ones were to guard against smallpox, which causes fever, boils and can be fatal; tularemia, which causes chills, aches, fatigue and typhoid-like symptoms, and Q-fever, which causes headaches, weakness and coughing.

In November 1997, the Pentagon awarded a $322 million, 10-year contract for the 18 vaccines to [DynPort Vaccine Company, LLC], a British-American venture. The plan sidestepped the knotty issue of immunizing troops, focusing instead on making and stockpiling vaccines for military personnel.

Exactly how the Pentagon would use its stored vaccines would depend on future events and threats.

Late last year, worry in the Pentagon about biological attacks turned to alarm as United States troops prepared to strike Iraq after President Hussein expelled Americans from international teams investigating his germ arsenal. On Dec. 15, Defense Secretary William S. Cohen announced that all 2.4 million American troops would get anthrax shots. Pentagon officials said the effort would take six years and cost $130 million.

Just at that moment, the theory of enemy countermeasures became real publicly for the first time. In December, Russian scientists stunned the biological world by disclosing that they had used genetic engineering to make a new anthrax microbe. It attacked blood cells and made Russia's vaccine useless.

Whether the organism was a laboratory curiosity or a battlefield weapon was unclear. The Russian scientists gave out no samples, so detailed analysis was impossible. But Western military officials were shaken and wondered whether the American anthrax vaccine was now obsolete, and whether the same was true of other vaccines in development.

''It's not just an academic debate anymore,'' said Jack Melling, director of the Salk Institute in Swiftwater, Pa., a vaccine center that does research for the Defense Department.

The news got worse in February. Ken Alibek, a top Russian defector, went public to assert that Moscow was working on a range of exotic germ weapons, including hybrids of the smallpox virus that cause profuse bleeding. If real, such germs could sow plagues that kill most victims.

The President -  Pushing a Plan To Save Civilians

Around that time, President Clinton became fixated on the emerging germ threat and ways to counter it among civilians, aides said.

Influences are said to have included the Iraqi crisis, the Russian claims, the intelligence reports and a novel, ''The Cobra Event'' (Random House, 1997), about a terrorist attack on New York City with a genetically engineered mix of the smallpox and cold viruses. Mr. Clinton was so alarmed by the book, his aides said, that he instructed his intelligence experts to assess its credibility and urged Speaker Newt Gingrich, Republican of Georgia, to read it.

Aides said the President and his National Security Council increasingly wrestled with the danger of biological attacks not only on troops abroad but also on American cities, states or even the entire country.

In January, in his State of the Union address, Mr. Clinton vowed to confront the hazard of germ weapons obtained ''by outlaw states, terrorists and organized criminals.''

In March, the White House held a secret exercise to play out what would happen if terrorists struck with one of the theoretical smallpox hybrids. The results of the war game were grim and fueled a Federal drive to find better ways to cope with such an attack.

In April, the President explored ways in which modern biology might help. He and his top officials met at the White House on April 10 with seven private scientists in the Truman Room, where Cabinet meetings are held. For an hour, participants say, the scientists discussed the germ topic and pushed for a vaccine stockpile.

Mr. Clinton's attending officials included the Secretary of Defense, the Attorney General, the Secretary of Health and Human Services, the Director of Central Intelligence and the national security adviser.

The scientists present were Dr. Frank E. Young, a former head of the Food and Drug Administration, who moderated the panel; [Dr. Joshua Lederberg (born 1925)], president emeritus of Rockefeller University; Dr. Lucille Shapiro, a biologist at Stanford University; [Dr. Jerome Maurice Hauer (born 1951)], head of emergency management for New York City; and [Dr. Barbara Hatch Rosenberg (born 1930)], a biological arms-control expert at the Federation of American Scientists, a private group.

The scientific panel also had two industry experts, both with financial ties to vaccine work.

One was a pioneer of genetic engineering who had decoded the smallpox virus and other microbes and used the meeting to push his own scientific agenda, participants said. But that researcher, [Dr. John Craig Venter (born 1946)], president of The Institute for Genomic Research, a nonprofit biotechnology group just outside Washington, said he simply urged the Government to step up support for the genetic mapping of deadly microbes. The insights, Dr. Venter added, would aid vaccine development and new methods of germ detection and treatment.

''The argument is that if we decipher these genomes it could be the ultimate deterrent,'' Dr. Venter said, referring to the ability to have so many avenues of defense that germ attacks would become futile.

Over the years, his institute had received millions of dollars in Federal support and is now gearing up to use more Government money to map the anthrax microbe as an aid to germ defense.

At the White House meeting, participants said, the business interests of another scientist were less well known.

[Dr. Thomas Patrick Monath (born 1940)] was identified in a White House announcement as a vice president of Oravax and a former official of the Centers for Disease Control and the United States Army Medical Research Institute of Infectious Diseases, the Government's top body for defensive germ-warfare studies.

A graduate of Harvard College and the Harvard Medical School, a world authority on yellow fever and other epidemics, Dr. Monath had devoted most of his career to public service.

At the meeting, he was viewed mainly through that lens, participants said, who added that they knew little about his company other than it worked on vaccines.

Based in Cambridge, Mass., Oravax was founded in 1990 to tap an emerging multibillion-dollar market in oral vaccines and antibodies to combat infectious diseases. But the small company kept having problems getting beyond research and bringing products to market.

By 1996 and 1997, its survival at stake, Oravax tried to win part of the Pentagon's expanding germ work as a subcontractor to make smallpox vaccines and others. By early this year, that work had failed to materialize and the company's stock price was down 90 percent from $10 a share in the initial public offering.

Memories of meeting participants varied, but no one could recall [Dr. Thomas Patrick Monath (born 1940)] telling the President of his company's financial interest in vaccine stockpiles -- a step he now insists that he took.

''The way to handle it is to be open, so people understand that I may have a potential bias,'' Dr. Monath said. ''I don't make it a business of taking advantage of situations in which I'm asked to participate to push the Oravax agenda.''

Many participants remember [Dr. Thomas Patrick Monath (born 1940)] arguing forcefully for stockpiling, a subject he had been asked by the panel's moderator to discuss.

[Dr. John Craig Venter (born 1946)] said the views of Dr. Monath, while strong, reflected the panel's consensus.

''Even through he was pushing harder than anyone else,'' Dr. Venter said, ''our recommendations to develop stockpiles of vaccines and medicines would have come out the same.''

A retired Army colonel, [Dr. Thomas Patrick Monath (born 1940)] was most likely the only scientist in the room who had deeply studied such problems for germ defense as enemy countermeasures.

That topic, participants say, was discussed little and in any case was overshadowed by [Dr. John Craig Venter (born 1946)]'s repeated assertions that genetic advances in theory had the power to solve these problems.

The Presidential briefing was such a hit that the experts were asked to take it on the road. In the following weeks, the scientists delivered their views to senior officials involved in vaccine issues at the Pentagon and the Department of Health and Human Services, participants said.

On May 6, the panel delivered a follow-up report to the President that, among other things, called for a stockpile of drugs and vaccines to protect millions of Americans against a variety of germs, up to 40 million against smallpox. The total cost over five years was estimated at $420 million.

Such a stockpile, the report said, could help ''reduce the death and illness 10 to 100 fold.''

A White House official who spoke on the condition of anonymity said the recommendation by the scientific panel simply encouraged the Administration to do what it was already contemplating. The official added that he saw no conflict of interest in [Dr. Thomas Patrick Monath (born 1940)]'s participation because his company had signed no Federal contracts for vaccine production.

Government ethics experts say that such private White House advisers are exempt from Federal conflict-of-interest rules and that Dr. Monath, even if he had an undisclosed interest, broke no law.

The White House official called Dr. Monath ''very knowledgeable,'' adding, ''The point of the meeting was to get a wide range of opinions from leading experts.''

The Pharmaceutical Research and Manufacturers of America, a Washington trade group that represents the nation's top 100 drug companies (Oravax is not among them), said it was never contacted by the White House for advice on the stockpile idea.

The Company -   Good News In Stock Market

Oravax at this time was increasingly desperate. In filings to the Securities and Exchange Commission, the company said it had won part of the Pentagon vaccine work.

Its stock price continued to slide. On May 4, the company put out a news release boasting of the contract, and the stock rose that day in heavy trading to $1.31, up from $1.00.

But in fact, Oravax had only a preliminary promise of possible work as a subcontractor to the British-American venture that had won the Pentagon contract, executives from both companies now agree.

Securities lawyers say such misrepresentations in S.E.C. filings are potential violations of Federal securities laws.

Later that month, as rumors and news reports suggested that the President was about to announce a civilian stockpiling effort, Lance K. Gordon, Oravax's president, issued a press release saying the company was prepared to take on the challenge.

''Although there is no guarantee that Oravax will be involved,'' Mr. Gordon said in the May 21 statement, ''the company believes it has the capacity to produce both smallpox and tularemia vaccines for civilian use.''

The next day, a Friday, Mr. Clinton announced the new push to create stockpiles of ''medicines and vaccines to protect our civilian population.'' He also praised gene research as ''very, very important'' to developing new ways of countering germ terror.

The same day, 2,413,100 shares of Oravax changed hands in the Nasdaq market, closing at $1.41, up 28 cents, or 25 percent. It was the stock's heaviest trading day ever. Later, the company issued a statement explaining the sudden activity, which it attributed to the President's action.

For [Dr. Thomas Patrick Monath (born 1940)], who owns or has options on 150,574 shares, the stock's price increase amounted to a profit on paper of $42,160.

The Battle  -   In Shaping Shield, Emphasis Changes

A quiet war erupted as Federal agencies and experts weighed in heavily for the first time. The Department of Health and Human Services, designated to oversee the stockpile, was ambivalent about the project, officials said. The agency faulted the initiative as simplistic, saying the plan put too little emphasis on the costly, painstaking work of improving the nation's public health network to cope with germ attacks.

Significantly, the agency found that no company was making, or would soon be able to make for civilians, the vaccines scheduled to be stockpiled. It therefore switched the emphasis to antibiotics. Though also potentially vulnerable to enemy countermeasures, these drugs were seen as having the benefit of fighting a variety of noxious germs.

Two weeks after the President's announcement, on June 8, the Government quietly began to back pedal. Even though the White House asked Congress for $51 million in the next fiscal year to develop ''a civilian stockpile of antidotes, antibiotics and vaccines,'' that same day Administration officials disclosed that vaccines had been ruled out for the moment. Why? Cheaper and more effective ones might appear in the next few years, the officials told reporters.

The developing plan has yet to address in detail how and where the medicines would be made, stored or distributed in a crisis.

As for Oravax, its stock is down, closing yesterday at 56 cents. And it still has no Federal stockpile work.

Despite the setbacks, many experts continue to back vaccines as important for germ defense and even hold out the possibility of wide civilian immunizations.

''Preventing an outbreak is always preferable to trying to suppress one after it has started,'' Senator Faircloth said.

As for the worry that an enemy might outwit vaccines with new or modified germs, vaccine supporters say that most of these enhanced germs are theoretical and would probably be less available and attractive to terrorists than known strains of deadly, dependable germs like unmodified anthrax and smallpox. If so, they say, vaccines are a good deterrent and a relatively cheap insurance policy.

Whatever their flaws or merits, vaccines continue to draw the interest of small companies eager to gain a foothold in an expanding area of the Federal budget.

On July 7, the State of Michigan approved the sale of the nation's only licensed maker of anthrax vaccine to a company led by Adm. William J. Crowe Jr., a former Chairman of the Joint Chiefs of Staff who was an important supporter of Mr. Clinton in the 1992 Presidential campaign.

Admiral Crowe's newly formed company has individuals with extensive drug industry experience and now has an inside track on at least $60 million in Pentagon contracts, officials of the Defense Department said. And while aiming at the military market, it wants to expand to civilian customers as well, company officials said, if that becomes possible in the years ahead. Companies drawn to the germ-defense business see the emerging civilian market as potentialy dozens of times larger than the military one and much more profitable.

How Vaccines and Antibiotics Work

Vaccines are made of dead or weakened germs. When they are injected -- or, in some cases, swallowed -- vaccines alert the body's immune system, which forms antibodies to fight a particular disease.

In contrast, antibiotics attack invading germs rather than work pre-emptively. Their chemical assaults weaken the invaders to help the immune system fight the infection. Typically, success requires daily doses. Antibiotics can work against a variety of microbes, making them more flexible than vaccines. But they cannot kill viruses, a crucial shortcoming.

To counter germ attacks, both vaccines and antibiotics can be administered in advance. But that step, while potentially effective, is laden with logistic, legal, cost and medical problems, especially with vaccines that in their current state of development carry some risk of causing accidental illnesses.

In theory, stockpiles of vaccines and antibiotics are useful for biological defense because the medicine can be administered quickly to help stop epidemics in progress, just as quick immunizations can help control natural outbreaks.

With vaccines, the Clinton Administration is pursuing a variety of options. It is vaccinating troops against anthrax, preparing to stockpile other vaccines for the military and embarking on a parallel stockpiling effort for civilians. For now, that step is caught up in debate and delay.

As anthrax exposures continue and the specter of smallpox has loomed on the horizon, many officials have begun discussing widespread vaccination against the two diseases in an effort to reduce public concern about terrorist threats.

But the vaccines now in use present a number of problems--ranging from lack of manufacturing capacity to side effects--that render large-scale vaccination programs problematic.

Medical researchers have been working on efforts to produce safer vaccines. But until now, drug companies have put relatively little money into what has been considered a low-margin, low-priority part of the business.

For both anthrax and smallpox, the side effects of the vaccines are serious enough that widespread vaccination could cause more damage than the diseases themselves unless the vaccines are used only after a major outbreak has begun.

Anthrax vaccination of soldiers has produced reports of severe side effects, such as bleeding and thyroid malfunction, and has been linked to six deaths.

Just what degree of risk there is from the vaccine, however, is unclear. Many medical authorities say it is safe, but some doctors have suggested it could be one of the causes of the mysterious Gulf War syndrome, which some troops sent to the Persian Gulf in the early 1990s have said they suffer from

Fear of the vaccine is perhaps greater than fear of anthrax. As many as 400 members of the U.S. military have been court-martialed or have resigned rather than submit to the vaccination because of the perceived risks. Some physicians share their misgivings.

“You won’t see me getting in line for the vaccine,” says [Meryl Jae Nass, MD (born 1951)], a longtime critic.

The vaccine is produced by only one manufacturer, BioPort Corp. of Lansing, Mich., and the technology is nearly 40 years old. Although the company is currently producing the vaccine, the Food and Drug Administration will not allow it to be shipped because of various deficiencies in quality control and manufacturing at the plant.

The vaccine is unusual in that it is not targeted at the bacterium itself, as are most vaccines, but at the toxin produced by the bacteria as they grow. That toxin produces the cellular damage that can lead to death from an anthrax infection.

The toxin has three major components: protective antigen, lethal factor and edema factor. When the toxin is released in the body, individual molecules of the protective antigen clump together on the surface of target cells to form a doughnut-shaped pore. This pore is then used by the other two components to enter the cell, where they are lethal.

The vaccine is designed to stimulate antibodies to the protective antigen, preventing it from attaching to cells. In theory, if the action of the toxin is blocked, then the immune system can eradicate the bacteria or they can be killed with antibiotics.

“We buy the individual some time to fight off the infection,” said microbiologist [Dr. Darrell Ray Galloway (born 1946)] of Ohio State University.

BioPort grows a strain of Bacillus anthracis that secretes only protective antigen. The bacterial culture is filtered--in a process much like making coffee in a filter pot--to collect the antigen along with any other materials that are secreted by the bacterium. The material that drips through the filter becomes the vaccine. It contains no bacteria, either dead or alive.

But the antigen does not stimulate a strong immune response. To get good immunity, six doses of the vaccine must be given at two-week intervals.

Critics fear that the other bacterial components collected along with the antigen may cause side effects, so research has focused on eliminating them.

“The interest is in more highly defined vaccines so one knows precisely what one is being immunized with,” Galloway said.

The Army has been working with the National Institutes of Health to use genetic engineering techniques to produce a pure antigen. Although both the military and the NIH have consistently refused to talk about their work, other experts say that human tests will begin early next year. That vaccine will also require multiple doses.

In his research, [Dr. Darrell Ray Galloway (born 1946)] also is targeting the toxin. But instead of using the antigen protein itself, he is injecting mice with the gene that causes the body to produce the protein. Researchers have been producing such DNA vaccines against a variety of diseases, and they are generally thought to produce a more powerful immune response and fewer side effects than standard protein vaccines.

He also uses the gene for the lethal factor in his vaccine. “We get a greater response with both than with one alone,” he said. Preliminary results in mice reported earlier this year indicate that the DNA vaccine can blunt anthrax infections, but Galloway must conduct many more tests, including vaccination of primates, before use of the vaccine in humans can be considered.

The most optimistic estimate would be 18 to 24 months before clinical trials could begin, he said.

The smallpox vaccine produces a different set of problems. Like the anthrax vaccine, it employs old technology--dating back to experiments by Edward Jenner, the pioneer of vaccines, in 1796.

Smallpox is produced by a virus called variola, but researchers do not use it to produce the vaccine. Instead, they use a related virus called vaccinia, which produces a disease called cowpox.

The normally mild infection produced in humans by the live vaccinia provides very good protection against smallpox--so good that the disease has been eradicated from nature. Today, variola is known to exist only in one laboratory each in the United States and Russia, although U.S. officials suspect that Iraq and perhaps other nations may also possess some virus stocks.

“The risk of its being used as a weapon is not very high, but it’s there,” said [Dr. Donald Ainslie Henderson (born 1928)] of Johns Hopkins University, who ran the global smallpox eradication campaign. “And if you got an outbreak, it would be a terrible global catastrophe.”

Existing stocks of the smallpox vaccine were grown in calf cells, collected and freeze-dried more than 30 years ago.

The vaccines are believed to still be effective, but they are contaminated with proteins and other materials from the cow cells that may produce adverse reactions in some individuals.

New Rules From the FDA

The FDA no longer allows vaccines to be grown in animal cells. The new contracts for vaccine production recently signed with several companies require that vaccinia be grown in human cells. That process is straightforward and should not introduce difficulties, and manufacturers assume that the new vaccine will be as effective as the old one.

“There are no technical hurdles here,” said Lance Gordon, chief executive of vaccine manufacturer [VaxGen, Incorporated]. “Everything that has to be done to make a state-of-the-art smallpox vaccine is technology already in use.”

But critics caution that a smallpox vaccine grown in human cells has never been tested and that assumptions don’t always hold up.

Vaccinia, moreover, can itself produce problems ranging from open sores all over the body to death.

The death rate is estimated to be as high as 2 in a million cases, meaning that if the entire U.S. population were vaccinated, about 600 people would die of the vaccine.

Inadvertent contamination of the eye--caused perhaps by touching the vaccination site and then the eye--can produce severe problems, including blindness.

Vaccinia itself is infectious. That’s a valuable trait in a vaccination program because it provides protection to people who weren’t directly vaccinated.

But in a modern society with large numbers of people whose immune systems have been damaged, by HIV infections or as a result of drugs taken for organ transplants, that contagion could be a major problem that likely would lead to additional deaths.

All told, vaccinating all Americans against smallpox could cause 3,000 severe adverse reactions and a much larger number of lesser problems, according to [Dr. Thomas Patrick Monath (born 1940)], an executive at British vaccine manufacturer Acambis.

If a terrorist group actually launched a smallpox attack, however, “we don’t have any choice as a society” other than to use the vaccinia vaccine, said [Dr. Darrell Ray Galloway (born 1946)].

The U.S. population now is almost entirely unvaccinated--the effect of the vaccine largely wears off after about 20 years, so most people who received the vaccine as children are no longer immune. An unprotected outbreak of smallpox potentially could kill millions of people, experts say.

A small number of researchers have been exploring the possibility of using a different type of vaccine, a killed-virus vaccine, which would eliminate the danger to immunosuppressed individuals.

But development of such a vaccine, like that for anthrax, has been hindered by lack of a market, and any product is still at least a couple of years from human tests.

For that reason, officials have pushed for a major expansion of the current smallpox vaccine supply. Right now, the country has about 15 million doses, not nearly enough to contain a major outbreak.

The World Health Organization once had 200 million doses in storage in Switzerland, but the international body ran out of money to keep them, and they were destroyed after President Reagan reduced U.S. payments to the United Nations. ‘

• CAMBRIDGE, MASSACHUSETTS—About 5 years ago, Thomas Monath’s career hit rock bottom. OraVax, the company he had struggled to build since 1992, was running out of money after its potential blockbuster drug for respiratory infections flunked a key clinical trial. By October 1998, the price of OraVax stock had dropped to a pitiful 25 cents; a few weeks later, NASDAQ delisted the company. With bankruptcy just around the corner, OraVax staff members were demoralized. “It was just so depressing,” Monath says. “It was awful.”
• But then a British company offered a shot at redemption. Peptide Therapeutics Group, equally unlucky in business but with more in the bank, bought OraVax for a mere $20 million. Rechristened Acambis, the new company went on to become the first big winner in the biodefense bonanza inspired by 11 September. In two deals worth $771 million, the U.S. government has picked Acambis for the critical task of producing smallpox vaccine for most of its citizens. Ten other countries have followed suit, and today, Acambis, which never turned a profit before the last quarter of 2002, is flush.
• By all accounts, Monath, as Acambis’s chief scientific officer, has been key to that success. He turned the budding interest in biodefense to his advantage before many others did, and his scientif ic credentials and friends in high places helped his inexperienced company win an order for a product that has become a key element of U.S. national security.
• Monath, 63, who served as a government scientist for 25 years, says his roller-coaster ride in the corporate world has taught him at least one lesson: Stick with the easy stuff. OraVax had put its money on a promising but unproven approach, enlisting so-called mucosal immunity to prevent infections. The smallpox vaccine that Acambis is now making was a much safer bet, as are most other vaccines Acambis has under development. “They all meet Monath’s principles,” he says. “They’re not high-tech.”

Muddy boots

• Running research for a biotech, even a hot one, can be mundane and at times boring. When Science shadowed Monath for a day recently, he sat through eight almost backto- back, coffee-fueled meetings and teleconferences, devoted to details such as which quality-assurance tests had been completed for a vaccine or how many slides to show during a meeting with the U.S. Food and Drug Administration. Most scientists have no idea of the minutiae of getting a product to the market, Monath says.
• The bland gray rooms where he spends most of his time couldn’t be more different from the African villages where Monath earned his stripes as a young scientist. Fresh from Harvard Medical School, he joined the Centers for Disease Control and Prevention (CDC) in 1968. He investigated yellow fever outbreaks in Nigeria for several years; in Sierra Leone, he tracked down the animal reservoir for the Lassa virus, which causes a deadly hemorrhagic disease that had recently been discovered. “Those were probably the most important experiences of my life,” he says.
• Monath went on to lead the CDC’s lab for vector-borne diseases in Fort Collins, Colorado, from 1974 to 1988. He then became an Army colonel and was named chief of virology at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in Fort Detrick, Maryland, where he worked on the development of vaccines and antivirals for insect-borne viruses and hemorrhagic fevers.
• He joined OraVax 4 years later in part because few vaccines or drugs ever seemed to make it out of the viscous government bureaucracy. “We never really controlled or prevented a disease,” he says. Producing vaccines commercially might do just that. And he couldn’t quibble with the remuneration; Monath now makes $280,000 a year and holds Acambis stock and options worth $2.5 million, according to a company spokesperson.
• Although some in his generation saw his departure to the world of quarterly results and Securities and Exchange Commission filings as a defection, Monath, who last year won the prestigious Walter Reed Medal, doesn’t seem to have lost stature as a virologist. “When I think of Tom, I still see a clinician-virologist with mud on his boots,” says David Franz, a former USAMRIID commander who is now at the Southern Research Institute in Frederick, Maryland. Monath is also well liked for his modest demeanor, ability to listen, and willingness to help others. “He’s really a super guy,” says [Dr. Clarence James Peters (born 1940)], a friend of Monath and director of the Center for Biodefense and Emerging Infectious Diseases at the University of Texas Medical Branch in Galveston.
• None of those qualities helped prevent the downward slide of OraVax, which had been founded by immunologists Marian Neutra and Jean-Pierre Kraehenbuhl 2 years before Monath joined it. Their idea was to harness immunoglobulin A (IgA) antibodies, which are produced in the membranes that line the mouth, nose, lungs, and gut and form the entryways into the body for most pathogens. “It was a great idea,” Monath says. “The problem is that it didn’t work very well.” For instance, 7 years of work on a vaccine against Helicobacter pylori, the cause of ulcers, still hasn’t resulted in success.
• The failed treatment for respiratory syncytial virus (RSV) that doomed OraVax was also based on IgA antibodies—in this case, administered in once-daily nose drops. RSV causes common and occasionally fatal infections in infants, and HNK20, as the product was called, had done well in mice and monkey experiments. But the trial, carried out among 614 infants in four countries in the Southern Hemisphere, failed to show that it reduced the risk of hospitalization, the key
• outcome. In retrospect, Monath says the dose was probably too low; OraVax was in such a hurry to score that it didn’t have time for more pilot studies. (A product based on a similar approach made $667 million last year for MedImmune, a Rockville, Maryland, company.)
• As the company’s financial situation was unraveling, Monath refocused research onto the more familiar areas of insect-borne viruses and biodefense. In 1997, OraVax had licensed a technique, developed by Thomas Chambers of Saint Louis University in Missouri, that Monath wanted to use to develop a series of new travel vaccines. Dubbed ChimeriVax, it’s based on a widely used live yellow fever vaccine called 17D, whose so-called envelope gene has been replaced with that of other members of its family, the flaviviruses. A ChimeriVax vaccine against Japanese encephalitis could enter phase III clinical trials next year; next in the pipeline is a vaccine against all four strains of dengue, a debilitating disease that’s on the rise throughout the tropics.
• So when a rather obscure flavivirus suddenly surfaced in New York City in the summer of 1999—West Nile—Acambis was ideally positioned to work on a vaccine. (There are even Web sites suggesting that Monath planted the virus himself.) In 2000, Acambis received a $3 million grant from the National Institutes of Health (NIH) to start work on a West Nile vaccine; today, the candidate is almost ready for its first clinical trials. As the disease becomes entrenched across the country—more than 4000 cases were reported last year—Acambis is looking at a potential moneymaker. Monath hopes that the vaccine becomes standard for elderly people in high-risk areas, much like flu shots.
• So far, the only product that’s making money for Acambis—and lots of it—is the smallpox vaccine. Monath got interested in biodefense as a market in the late 1990s. At the time, smallpox eradication champion D. A. Henderson and others were warning loudly against the risk of a bioterrorist attack, and the government had begun to take notice. Initially, Acambis had hoped to produce vaccines for the military, but in 1998, talks between the company and DynPort, the Army’s main vaccine contractor, broke down.
• Meanwhile, the U.S. Department of Health and Human Services (HHS) decided it wanted its own vaccine to protect civilians. In 2000, it ordered 40 million doses of its own—at the time, deemed enough to deal with an attack—to be delivered by 2006. To the surprise of many, it picked Acambis, one of the companies that had developed a plan to produce a new vaccine. Then came 11 September, and everything changed. Within a few weeks, the government upped its order to 54 million doses. And in November 2001, it decided to purchase another 155 million doses. Again, Acambis, whose stock price doubled in the 3 months after the attack, won the contract.

One-stop smallpox shopping

• The new smallpox vaccine is essentially the same as the one used for decades to control the disease in the United States, a strain of the vaccinia virus called New York City Board of Health. But instead of a mixture of viruses harvested from the skin of calves, the Acambis vaccine is a single clone, produced in a cell culture. Churning out the staggering amount was too much for the small company, so it teamed up with Baxter, an international company, which produced the smallpox vaccine in a plant near Vienna, Austria. (The entire batch was finished last May, 5 months short of the original deadline, but it has not yet been delivered to the government pending resolution of a labeling issue.)
• Monath says Acambis couldn’t have won the huge contract if its proposal hadn’t been competitive, but he concedes that his long tenure with CDC and USAMRIID and close friendship with many key off icials in the small biodefense arena gave him an edge. “I grew up with many of these people,” he says. “I feel very confident calling up D. A. Henderson or Phil Russell,” two of HHS’s top bioterrorism advisers. At least some of his competitors don’t think Monath has an unfair advantage. Says Franklin Top, MedImmune’s medical director and a former director of the Walter Reed Army Institute of Research, “Those guys are picking his brain too. That’s just the way it goes.”
• But Monath’s networking did lead to allegations of impropriety: In 2001, The New York Times reported that Monath had not disclosed his own interests when he served on a panel that advised President Bill Clinton to ramp up biodefense vaccine production. Monath says the allegations are false, but even so, says Peters, “that hurt his reputation,” although there was no commercial fallout.
• Acambis is now trying to develop a milder version of the smallpox vaccine, called modified vaccinia Ankara (MVA), for those at increased risk of side effects. It has also partnered with Cangene in Winnipeg, Canada, to sell that company’s antibody treatment for vaccinia’s side effects. (With the three products combined, Acambis hopes to offer anxious governments onestop shopping.)
• But success in the biotech world can be fickle, and competition is intense. Acambis has yet to show that it is more than a one-hit wonder, says Ken Trbovic, a biotech analyst and vice president at C. E. Unterberg, Towbin in New York City. For instance, another company, Bavarian Nordic, is also developing MVA and is confident that it has an edge. Both companies won a $9 million NIH development contract earlier this year, and both hope to win the main prize: a contract to produce 30 million doses of MVA.
• The ChimeriVax vaccines face another potential wrinkle. The yellow fever vaccine that the technology uses had always been considered extremely safe, but in the past few years, there have been a handful of serious, sometimes fatal, cases of a yellow fever–like disease among travelers who received the vaccine. The causes are unknown; a U.S. advisory panel, of which Monath is a member, is monitoring the situation closely. Monath believes that Acambis’s vaccines are less likely to have this problem, because their envelope protein, which determines where a virus can attack, is different from the one in the old vaccine. But it’s a concern nonetheless.
• For the moment, however, Acambis is basking in its success; the smallpox money will enable it to keep going for a while without the stress of the OraVax days. And nature itself may create the next business opportunity. Like many other companies, Acambis is already working on a vaccine for severe acute respiratory syndrome, and Monath says he wouldn’t be surprised to see yellow fever reemerge in the United States; the right mosquito species are already here. Says Monath: “I think West Nile was just a lesson.” –MARTIN ENSERINK

May 11, 2005 (CIDRAP News) – An initial human trial of a West Nile virus (WNV) vaccine has yielded promising results, officials said today.

In the double-blind, randomized trial, all but one of the people who received the vaccine developed antibodies to it, according to an Associated Press (AP) report quoting Dr. Thomas Monath, chief scientist at Acambis, the company that created the vaccine.

Results of the trial were to be presented today at the National Foundation for Infectious Disease's (NFID) annual conference in Baltimore, 5 years after the company began researching WNV vaccines. Acambis had received a $3 million grant from the National Institutes of Health. Testing on volunteers began in 2003, the AP reported.

Acambis created the ChimeriVax-West Nile vaccine by combining some genes from WNV with a licensed yellow fever vaccine, the AP story said. The yellow fever virus is a relative of the West Nile virus, and the yellow fever vaccine is known to be safe.

The phase 1 clinical trial involved 80 volunteers. Thirty people received a single high dose of the vaccine, 15 were given a low dose, 30 received a placebo, and 5 received a yellow fever vaccine, Acambis officials said in a news release.

By 28 days after vaccination, 96% of the high-dose group and 100% of the low-dose group had a measurable antibody response, Acambis reported. The company reported mean antibody titers of 1280 and 1350, considered high, in the respective groups.

The rate of vaccination side effects varied relatively little among the high-dose group (40%), the low-dose group (46.7%), and the placebo groups (43.3%), Acambis announced. No serious adverse events were blamed on the vaccine.

"We are encouraged by the immune response generated by trial subjects who were vaccinated with a single inoculation," Monath said in the news release.

The next phase of testing will include a larger sample with more older adults, the AP reported. Provided the second phase goes well, the third phase will involve thousands of people.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said he was impressed by the percentage of patients who showed high levels of antibodies, but he cautioned that these are early findings, the AP reported.

Use of the proven yellow fever vaccine to create a safe hybrid could shave years off vaccine development, Fauci added.

No vaccine has been approved for West Nile, which first appeared in the United States in New York in 1999 and has spread to every contiguous state except Washington since then. WNV caused at least 2,470 illnesses and 89 deaths in the United States last year, according to the Centers for Disease Control and Prevention (CDC).

Most people who contract the virus are don't become ill, but about 20% can experience fever, headache, nausea, and vomiting. About 1 in 150 suffers a severe illness, according to the CDC.

When the Pan American Health Organization put out an alert last May about the first confirmed cases of Zika virus infection in Brazil, the news barely registered. After all, compared with other mosquito-borne viruses, such as potentially life-threatening dengue and yellow fever, Zika seemed pretty harmless. Only 20% of people infected with Zika even become ill, and their symptoms tend to be mild—fever, rash, joint pain, and conjunctivitis.

But in January, nine months after the organization raised the alarm, doctors in Brazil reported a disturbing trend that coincided with Zika’s spread across the country. Since October 2015, more than 4,000 babies in Brazil had been born with abnormally small heads and brains—a rare condition known as microcephaly. Although further analysis lowered that figure by 462 cases, the sharp rise nonetheless has experts worried that Zika could be to blame. For comparison, Brazil reported just 147 cases of microcephaly in 2014.

Zika is also being blamed for an uptick in cases of Guillain-Barré syndrome, a potentially life-threatening disorder in which the body’s immune system attacks the central nervous system and causes paralysis. As with microcephaly, the evidence connecting Zika and Guillain-Barré is still circumstantial. Nevertheless, the link is strong enough for the World Health Organization to declare the Zika outbreak a public health emergency of international concern.

Margaret Chan, WHO’s director-general, said earlier this month that the virus is “spreading explosively” through the Americas, with cases of active virus transmission in at least 26 countries and territories in the Americas. Panic over the virus has prompted health officials in some countries to take the drastic measure of advising women to delay pregnancy for months or longer. In El Salvador, Deputy Health Minister Eduardo Espinoza asked women to avoid becoming pregnant until 2018.

With Zika making headlines for the past month, scientists have been scrambling to get a handle on the virus. Industry, government, and academic scientists have all announced efforts to develop and test treatments and vaccines. But the path ahead for these researchers is long and full of pitfalls. Even though Zika has been around for almost 70 years, surprisingly little is known about the virus and its basic biology. A PubMed search for “Zika virus” turns up mostly case studies.

What we do know is that Zika is a flavivirus, a member of the same family as dengue, yellow fever, and West Nile virus. Zika is primarily transmitted via bites from infected mosquitoes, but in recent weeks doctors have reported that the virus can be sexually transmitted as well.

It was first identified in a monkey in Uganda’s Zika forest in 1947, but only a handful of human Zika cases were reported until a 2007 outbreak in Micronesia’s Yap Island. An outbreak in French Polynesia followed six years later. Last November officials in that country reexamined the cases of microcephaly that followed the outbreak. Before the outbreak, about one case of microcephaly was reported each year. In 2014–15, officials found 17 cases of fetuses and infants with “central nervous system malformations,” which includes microcephaly.

As the case connecting Zika to serious health effects builds, the world would love a vaccine or treatment for the virus. But because so few have studied Zika, drug developers currently have few tools to work with. For example, there’s no commercially available, U.S. Food & Drug Administration-approved test to screen for Zika virus.

Tracking Zika in people is hard because it’s difficult to determine that they’re infected with Zika and not a related flavivirus or that they’re not infected with more than one virus, says Priscilla L. Yang, a flavivirus expert at Harvard Medical School. Simultaneous infection with Zika and another virus could cause health effects that haven’t been seen before.

Scientists can use polymerase-chain-reaction-based methods to distinguish Zika from other flaviviruses. But those tests are accurate only during the short window patients still have the virus in their system—about seven days after infection. By the time a patient has symptoms that warrant a visit to the doctor, the virus is no longer circulating in their bloodstream, Yang notes.

Another option is to look for antibodies against the virus. But Zika and dengue are closely enough related that antibodies to Zika also recognize dengue and vice versa. Making a definitive diagnosis based on antibodies is possible but becomes time-consuming and laborious, Yang says.

For scientists who have compounds that might be effective against Zika, actually testing them has been tough. “We have small molecules that seem to be broadly acting against dengue and West Nile virus,” Yang says. “We want to test them, but getting access to the live virus has been hard.” She’s heard that certain labs known to have the Zika virus have been bombarded with hundreds of requests from researchers.

Even if someone manages to access the live virus and can find a compound that kills it in cells, the researcher will hit another roadblock: To date, no one has published practical animal models of Zika virus to screen potential therapies against. Yang points to a paper from the 1970s in which scientists did an intracranial injection of Zika virus in newborn mice, but she notes that is a poor model because many small molecules can’t slip past the blood-brain barrier.

“We’re basically starting from scratch on this one, unfortunately,” says [Sina A Bavari (born 1959)], chief scientific officer (CSO) at the U.S. Army Medical Research Institute of Infectious Diseases. Bavari and colleagues are currently working with pharma companies to see if they have any compounds that inhibit Zika replication in cells.

They’re primarily interested in compounds that have passed the hurdles of Phase I or Phase II clinical trials but are sitting idle for business reasons. That’s because it can take upward of a year and a half just to get a new compound ready for Phase I. “My worry is that by the time we get something out the door, this outbreak will have already burned out,” Bavari says.

Scientists are also grappling with this question: If only 80% of people infected with Zika have symptoms, who would get the treatment? The most vulnerable patients are pregnant women, but Bavari points out, there’s a high bar when it comes to approving a medication that can be given to them. “They don’t even want to drink caffeine,” he says.

Other scientists are working to develop a vaccine against the Zika virus. Earlier this month President Barack Obama said he would ask Congress for $1.8 billion to combat Zika at home and abroad. Of those funds, $200 million would be used for vaccine development. The U.S. National Institute of Allergy & Infectious Diseases, Sanofi Pasteur, and NewLink Genetics are among the heavy hitters in the vaccine field who’ve said they’ll step up to the plate.

Even so, it could take three to five years before a vaccine is ready, experts say. [Dr. Thomas Patrick Monath (born 1940)], CSO of [NewLink Genetics Corporation]’s infectious disease division, led that firm’s efforts to develop an Ebola vaccine and was CSO at Acambis, where he worked on vaccines for dengue and yellow fever. Monath tells C&EN he thinks a large field trial of 10,000 to 20,000 people across multiple sites will be necessary to determine efficacy once a Zika vaccine is developed. “Only after those trials would you contemplate doing studies in pregnant women,” he says.

Monath also says because so many people who are infected with Zika never show any symptoms, it is more difficult to determine whether the vaccine has actually prevented infections. Still, he thinks a large enough trial should be conclusive.

But some scientists say the emphasis on vaccines is misplaced. “We just don’t know enough about Zika virus right now to run around and vaccinate people,” Bavari says. “Understanding the immunopathology and immunology behind it would be really prudent before starting a full vaccination program.”

Harvard’s Yang says developing a vaccine for every emerging virus is impractical. “Vaccines are, for the most part, specific. You have one virus, and you have one vaccine for it,” she explains. “I don’t think we’ll ever have the luxury of enough resources to get a vaccine against every single possible emerging virus or enough time to do it in a reactive way.”

One area that’s not getting as much attention, she says, is development of broadly acting antivirals that could keep a virus in check while the immune system fights it off. Classical antivirals go after a single viral enzyme, but viruses are quick to develop resistance to them. “If people could identify targets that have the potential to be effective against multiple viral pathogens, it could be game-changing,” Yang says.

[Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960)], a Vanderbilt University professor who works on antivirals, agrees. “There are so many viruses out there. We need to be working on a much more broad-spectrum approach to infectious disease,” he says. “If we can develop more tools to combat broad categories of viruses, I think we would be much better off than we are today.”  [ Note - [Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960) passed July 25, 2017 ]

In the meantime, scientists agree that the research community needs to be more organized if it’s going to have a real shot at combating Zika. Yang thinks the first steps should be figuring out how to get the necessary reagents to the labs that need them and agreeing on standards so they can compare results and learn from each other’s work. “If you actually want to have some sort of impact, we all need to work together,” she says. In an encouraging sign, earlier this month, major scientific institutions and top research journals agreed to share data relevant to Zika virus.

Bavari agrees scientists need to be better at organizing their efforts, but he has doubts about the direction the community is taking. “The outbreak is moving so quickly that I am worried people will jump and we won’t do the correct research,” he says. 

Recalcitrant Mosquito Blamed For Zika’s Spread

With a treatment or vaccine for Zika potentially years away, countries are relying on mosquito control to curb the virus’s spread. Aedes aegypti mosquitoes, which inhabit tropical and subtropical regions, have been named as the culprit in transmitting the virus.

But getting rid of Aedes aegypti is extremely difficult because the mosquitoes don’t seem to be affected by most spraying regimens, says Joseph M. Conlon, an entomologist and technical adviser to the American Mosquito Control Association. According to Conlon, Aedes aegypti feed during the day, but pesticides must be sprayed at dawn or dusk. Also, mosquitoes like to come indoors to feed. So, unless pesticides are sprayed inside homes, chances are good they’re not getting to the insects.

These mosquitoes are very small, and you can’t feel the bites. “Oftentimes you don’t even know you’ve been bitten,” Conlon says.

To get rid of the biting bugs, it’s critical to eliminate any standing water. “I’ve seen Aedes aegypti breeding in discarded soda bottle caps,” Conlon says. “They’re survivors.”

Despite Aedes aegypti’s survival skills, the mosquitoes actually have a fairly limited flight range of about 150 meters. That has made some scientists suspect that because Zika has spread so quickly, the more common Culex mosquito may be transmitting the virus as well. The theory is currently being investigated.

“If that is true, that brings this to a whole different level,” Conlon says. Culex mosquitoes have a much larger range, he notes, but they can usually be controlled through common mosquito abatement programs. ◾

Devens, MA, USA; August 22, 2019— Crozet BioPharma, LLC (Crozet) announced today a $10.8 million total value partnering agreement with Public Health Vaccines, LLC (PHV) to advance the development and manufacture of a vaccine against the Nipah virus, listed as a priority pathogen by the World Health Organization.1

The Coalition for Epidemic Preparedness Innovations (CEPI) has granted PHV funding to support pre-clinical development, manufacturing, clinical advancement through Phase 2, and establishment of an investigational stockpile of the vaccine candidate worth up to $43.6 million.2 PHV, a Cambridge-based biotechnology firm, has partnered with Crozet to provide core technical and strategic development services to the program.

Crozet, in collaboration with PHV, will engage its expert team of vaccine developers and manage a coalition of partners to develop the rVSV-Nipah vaccine. This includes design and oversight of critical technical elements of the development program including manufacturing and quality control of the vaccine, nonclinical safety and efficacy studies, tests for measuring immune responses, and Phase 1 and 2 clinical trials.

Dr. Thomas Monath, Managing Partner and Chief Scientific Officer at Crozet Biopharma said: “The Crozet team spent several years developing the successful rVSV-ZEBOV Ebola vaccine. That expertise will greatly facilitate advancement of the rVSV-Nipah vaccine. We look forward to our partnership with PHV, support from CEPI, and the opportunity to work with an extraordinary coalition of experts to develop a rVSV-Nipah vaccine candidate. “

The vaccine candidate was developed by [Dr. Heinz Ulrich Feldmann (born 1959)] within the Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and has been licensed to PHV by NIAID. The recombinant vesicular stomatitis virus (rVSV) vaccine candidate expressing a type of Nipah-virus protein (known as glycoprotein G) is designed to induce protection against the virus after a single dose.

Nipah virus, a bat-borne virus, can spread to humans and cause brain inflammation and pneumonia with a high mortality. Epidemics of the disease have emerged during the last 20 years in India, Southeast Asia and the western Pacific.

Dr. D. Gray Heppner, Crozet’s Chief Medical Officer said: “Nipah virus infection causes a dreadful disease for which there is no treatment. The Crozet team believes all people at risk of Nipah disease deserve the protection of a safe, effective vaccine.”

• About Crozet BioPharma
  • • Crozet BioPharma, LLC, headquartered in Devens, Massachusetts, is a biotechnology company developing medical countermeasures for infectious disease and cancer. Crozet’s team includes individuals with deep industry experience demonstrated by their collective track record and experience developing ten licensed vaccines. While at NewLink Genetics, the Crozet team enabled transfer of the technology to Merck, obtained over $100 million in funding and supported Merck’s advanced development of the rVSV-EBOV Ebola vaccine. Most recently, Crozet has partnered with PHV to support delivery of PHV’s rVSV-Marburg and rVSV-Nipah vaccine candidates. For more information, visit the company’s website at www.crozetbiopharma.com.
• About PHV
  • • Public Health Vaccines, LLC. (PHV), headquartered in Cambridge, Massachusetts, is a privately-held biotechnology company developing vaccines for the prevention and control of emerging infectious diseases. For more information, visit the company’s website at www.phvaccines.com.