• Shiu-Lok Hu, American Molecular biologist. Grantee unites states department Defense, National Institutes of Health, 1981. Member American Association for the Advancement of Science, American Society Virology, American Society Microbiology, Phi Beta Kappa.

• Background :   Hu, Shiu-Lok was born on November 10, 1949 in Hong Kong. Came to the United States, 1967. Son of I-Ping and Pie (Wang) Hu.

• Education :   Bachelor, University of California, Berkeley, 1971; Doctor of Philosophy, University of Wisconsin, Madison, 1978.

• Career :   Postdoctoral fellow, Cold Spring Harbor (New York) Laboratory, 1978-1981; senior scientist, Molecular Genetics, Inc., Minnetonka, Minnesota, 1981-1983; director molecular biology, Molecular Genetics, Inc., Minnetonka, Minnesota, 1983-1984; laboratory director, [Oncogen Company], Seattle, 1985-1989; executive director virology, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, since 1990. Research associate professor microbiology, U. Washington, Seattle, since 1988.

• Achievements :   Shiu-Lok Hu has been listed as a noteworthy Molecular biologist by Marquis Who's Who.

• Membership :   Member American Association for the Advancement of Science, American Society Virology, American Society Microbiology, Phi Beta Kappa.

Connections

Married Gail Ellen Anderson, December 20, 1984. Children: Emily Chu-Yuin, Alice Chu-Lin.

• Father :   I-Ping Hu

• Mother :   Pie (Wang) Hu

• Spouse :   Gail Ellen Anderson

• child :   Emily Chu-Yuin Hu

• child :    Alice Chu-Lin Hu

Experience

• University of Washington

  1. • Professor  /   Mar 1997 – Present  ( 24 yrs 9 mos )

• Bristol-Myers Squibb

  1. • Executive Director  /   1985 – 1997  ( 12 yrs )

Education

• University of Wisconsin-Madison

  1. • Doctor of Philosophy (PhD)  /   Molecular Biology  /   1971 – 1978

• University of California, Berkeley

  1. • Bachelor of Arts (BA)  /   Biochemistry  /   1967 – 1971

During 1991 significant headway continued to be made in simian immunodeficiency virus (SIV) vaccine research. The marked susceptibility of macaques to challenge infection with titered biologic and molecularly cloned stocks of certain strains of SIV, and the reliable induction of simian AIDS within a relatively short time (6-24 months) make this model suitable for testing the safety and immunogenicity and, most importantly, the protective efficacy of various vaccines against bloodstream infection and disease. In addition, SIV vaccines have been tested against genital and rectal routes of infection. This past year has seen a confirmation of the validity of this model for AIDS vaccine development. Protection against bloodstream infection by inactivated whole SIV vaccines has been confirmed and extended to include heterologous strains. Attenuated live virus and passive transfer of immune sera have also protected against systemic infection. The first reports of immune protection using recombinant SIV envelope vaccines have appeared. However, bearing in mind several recent failures to protect with recombinant SIV vaccines, we evidently need to learn much more about these novel vaccine strategies. Protection against rectal infection but not against vaginal mucosa! infection has been observed, raising important questions about mucosa! immunity. Solid protection against intravenous (i.v.) infection with lymphocyte associated SIV also has yet to be achieved. Finally, the recent revelation that immunization with uninfected human cells protects macaques against i.v. infection with SIV mac raises the interesting question about the role of anticellular antibodies in protective immunity. This review will summarize the SIV vaccine field, now several years old, and will highlight the most recent developments. The amount of unpublished information included in this review might render a more fitting title, '1992 - a year in preview'.

Inactivated virus

Several groups in the United States [1-5] (P. Johnson, personal communication, 1991), United Kingdom (M.P. Cranage, E.J. Stott, KA Kent, et al., submitted for publication) [6], Sweden [7], Germany (C. Stahl-Hennig, G. Voss, S. Nick, et al., submitted for publication; S. Hartung, S.G. Norley, J. Ennen, et al., submitted for publication) and the Netherlands (A Osterhaus, personal communication, 1991) have reported successful protection of macaques against experimental SIV infection and/or disease by inactivated whole SIV vaccines (Table 1). Protection of macaques against HIV- 2 challenge infection with an inactivated whole HIV- 2 vaccine [8] is covered in another chapter. Efficacy is ~90% in these trials, which now include over 100 monkeys, mostly rhesus (Macaca mulatta), cynomolgus (M fascicularis) and pig-tailed (M nemestrina) macaque species. By contrast, all controls have become persistently infected with the same challenge dose of SIV. Special laboratory conditions for obtaining successful protection include challenge with a relatively low dose, 10-200 animal infectious doses (ID) of homologous cell-free virus given intravenously (i.v.) or intramuscularly (i.m.) within 2-4 weeks after the last boost. Higher challenge doses ( > 103 ID), when tested, have not been protected against by the inactivated virus vaccines [ 1,3]. Virus for the SIV vaccine trials in the United States was grown in human Tcell lines (for example, HUT-78, CEM), whereas, to maintain maximum virulence, the live virus for challenge was usually grown in fresh human T-cells. The European Community (EC) investigators have used a common stock of formalin-inactivated SIV mac251 vaccine prepared from virus grown in a human T-cell line (C8166) and a homologous challenge stock of SIVmac25(13 2H), also grown in C8166 cells after passage through a rhesus monkey. Successful vaccines were achieved by inactivating the whole virus with formalin, ~-propiolactone, or detergent. There has been no incidence of residual live virus in any of the inactivated vaccines. Successful whole virus vaccines were made from either uncloned biologic isolates or molecular clones of SN mac or SNsm· An inactivated molecular clone of SN mac (BK28) could protect against challenge with an uncloned biologic isolate of SN mac (M. DeWilde, personal communication, 1991), and an inactivated molecular clone of SN8m (H-4) could protect against the uncloned homologous strain (SN8mE660) (P. Johnson, personal communication, 1991). Virus pelleted from culture media without further purification, and virus purified by sucrose gradient or column chromatography were used in the successful wholevirus vaccines. The total amount of virus antigen used to confer protective immunity ranged from approximately 500 μg to 3.0 mg, and the schedule of immunizations consisted of a maximum of five inoculations over a 13-month period to a minimum of three inoculations over a 2-month inteival. In a recent study comparing two total doses ( 400 μg and 2.0 mg) of the EC formalin-inactivated SN mac vaccine, one out of four monkeys receiving the lower dose and four out of four monkeys receiving the higher dose were protected against challenge infection with 33 50% infectious dose (ID50) of homologous virus (S. Hartung, S.G. Norley, J. Ennen, et al, submitted for publication). Adjuvants used include muramyl dipeptide [MOP; Syntex adjuvant formulation, monophosphyl lipid A plus 'cell wall skeletons'(RIBI)], alum, complete and incomplete Freund's adjuvant (CFA, IFA), immunostimulating complex (ISCOM) and Quil A MDP has been the most widely used adjuvant (SAF-1 Syntex, kindly provided by Dr AC. Allison, Syntex). At the German Primate Center ( C. Stahl-Hennig, G. Voss, S. Nick, et al, submitted for publication), it was shown that over 50% (four out of seven) of monkeys were protected against SN infection using a vaccine formulation (Tween ether-treated whole virus adsorbed to. alum) of the type used for many years to vaccinate humans against influenza virus. With all the vaccines tested so far antibody levels declined rapidly after each boost. In vaccine-protected monkeys, antiviral antibodies declined after challenge, reaching minimal levels by 4-6 months post-challenge. No adverse reactions have occurred in any of the vaccinated animals.

Duration of protection

Results from three groups suggest that vaccinated monkeys remain partially protected for as long as 8 months after the last boost. In one US study (M. Murphey-Corb, personal communication, 1991), two out of four SN8m-vaccinated monkeys were susceptible to challenge infection with 10 ID of the same virus 8 months after the last boost. In a second trial (M. Murphey-Corb, personal communication, 1991), using an improved whole SNsm vaccine, five out of five monkeys were still protected against the homologous virus 8 months after the last boost. However, this protection

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