New Multivalent Vaccine

A vaccine has been tested in recent trials to determine if people with previous Lyme disease exposure and no residual after affects would be protected against future exposure to Lyme disease.

The Lancet, a publication that has printed horrible commentary about Lyme patients, volunteer patient advocates, organized Lyme groups and doctors treating Lyme disease, has published the following.

Lancet Infect Dis. 2013 Aug;13(8):680-9. doi: 10.1016/S1473-3099(13)70110-5. Epub 2013 May 10.

Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial.

Wressnigg N¹, Pöllabauer EM, Aichinger G, Portsmouth D, Löw-Baselli A, Fritsch S, Livey I, Crowe BA, Schwendinger M, Brühl P,Pilz A, Dvorak T, Singer J, Firth C, Luft B, Schmitt B, Zeitlinger M, Müller M, Kollaritsch H, Paulke-Korinek M, Esen M, Kremsner PG, Ehrlich HJ, Barrett PN.

Author information

¹Vaccine R&D, Baxter BioScience, Vienna, Austria.

Abstract

Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults.

Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18-70 years who were seronegative for B. burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 μg, 60 μg, or 90 μg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9-12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1-6, as established by ELISA. This study is registered with ClinicalTrials.gov, number NCT01504347.

300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 μg, 51 to 60 μg, and 50 to 90 μg doses), and 149 to non-adjuvanted vaccines (50 to 30 μg, 49 to 60 μg, and 50 to 90 μg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0·54 [95% CI 0·41-0·70]; p<0·0001) and of moderate or severe systemic reactions (0·35 [0·13-0·92]; p=0·034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 μg adjuvanted formulation had the best tolerability profile; only headache (five [10%, 95% CI 4-20] of 50), injection-site pain (16 [32%, 21-45]), and tenderness (17 [34%, 23-47]) affected more than 6% of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1-6 after the first three vaccinations (range 6944-17,321) and booster (19,056-32,824) immunisations. The 30 μg adjuvanted formulation induced the highest antibody titres after the booster: range 26,143 (95% CI 18,906-36,151) to 42,381 (31,288-57,407).

The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin.

Baxter.

Comment in

Lyme disease vaccination: safety first - authors' reply. [Lancet Infect Dis. 2014]
Lyme disease vaccination: safety first. [Lancet Infect Dis. 2014]
Lyme disease vaccination: are we ready to try again? [Lancet Infect Dis. 2013]

PMID: 23665341 [PubMed - indexed for MEDLINE]

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Comment by Stricker/Johnson

Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial.

Wressnigg N.Lancet Infect Dis. 2013.1 comment

Raphael Stricker2013 Dec 19 00:51 a.m.edited 0 of 1 people found this helpful

Our Letter to the Editor of Lancet Infectious Diseases (2014;14:12) expressed concern about the safety of the new Lyme OspA vaccine from Baxter Bioscience. This concern is based on safety issues related to the previous Lyme OspA vaccine, Lymerix®, which was taken off the market after these safety issues surfaced, as outlined in our letter.

In their response to our letter, the employees of Baxter Bioscience who studied the new vaccine made the following comment: “There are no data in Stricker and Johnson’s cited publications that support the statement that ‘joint-reactive and nerve-reactive antibodies’ are induced in human beings vaccinated with OspA antigen.” This comment is misleading because OspA vaccine-related antibodies against nerve and joint tissue have been detected in animals and humans described in the references below. Furthermore, the fact that antibodies with unknown reactivity were induced by Lymerix® vaccination presents an unresolved safety issue for the new OspA vaccine, and this issue was not addressed by the Baxter Bioscience employees who studied the vaccine.

Once again, the willingness of Baxter Bioscience to ignore legitimate safety concerns bodes ill for the new Lyme vaccine.

Raphael B. Stricker, MD, Lorraine Johnson, JD, MBA

References

Stricker RB. Lymerix® risks revisited. Microbe 2008;3:1-2.
Smith P, Gaito A, Marks DH. Transcript of FDA Lymerix Meeting, Bethesda, MD, January 22, 2002. Available at: http://www.lymediseaseassociation.org/index.php?option=com_content&view=article&id=532:lymerix-meeting&catid=129:hhsfood-a-drug-administration-fda&Itemid=531
Croke CL, Munson EL, Lovrich SD, et al. Occurrence of severe destructive Lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi. Infect Immun. 2000;68:658–63.
Rose CD, Fawcett PT, Gibney KM. Arthritis following recombinant outer surface protein A vaccination for Lyme disease. J Rheumatol. 2001;28:2555–7.
Latov N, Wu AT, Chin RL, Sander HW, Alaedini A, Brannagan TH. Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi. Periph Nerv Syst. 2004;9:165–7.
Alaedini A, Latov N. Antibodies against OspA epitopes of Borrelia burgdorferi cross-react with neural tissue. J Neuroimmunol. 2005;159:192–5.
Souayah N, Ajroud-Driss S, Sander HW, Brannagan TH, Hays AP, Chin RL. Small fiber neuropathy following vaccination for rabies, varicella or Lyme disease. Vaccine 2009;27:7322-5.
Marks DH. Neurological complications of vaccination with outer surface protein A (OspA). Int J Risk Saf Med. 2011;23:89-96.
Molloy PJ, Berardi VP, Persing DH, Sigal LH. Detection of multiple reactive protein species by immunoblotting after recombinant outer surface protein A Lyme disease vaccination. Clin Infect Dis. 2000;31:42-7.
Fawcett PT, Rose CD, Budd SM, Gibney KM. Effect of immunization with recombinant OspA on serologic tests for Lyme borreliosis. Clin Diagn Lab Immunol. 2001;8:79-84.
Hanson MS, Edelman R. Progress and controversy surrounding vaccines against Lyme disease. Expert Rev Vaccines 2003;2:683–703.
Nigrovic LE, Thompson KM. The Lyme vaccine: a cautionary tale. Epidemiol Infect. 2007;135:1–8.
Nardelli DT, Munson EL, Callister SM, Schell RF. Human Lyme disease vaccines: past and future concerns. Future Microbiol. 2009;4:457-69.
Smith P. Remarks to Vaccines and Related Biological Products Advisory Committee, Bethesda, MD, January 31, 2001. Available at: http://www.lymediseaseassociation.org/index.php?option=com_content&view=article&id=262:vaccine-remarks&catid=80:controversy&Itemid=76

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Another Comment by Stricker/Johnson

Lyme disease vaccination: safety first - author's reply.

Lantos PM.Lancet Infect Dis. 2014.1 comment

Raphael Stricker2013 Dec 30 2:09 p.m. 1 of 1 people found this helpful

Raphael B. Stricker, MD* and Lorraine Johnson, JD, MBA*

*International Lyme and Associated Diseases Society, P.O. Box 341461, Bethesda, MD 20827-1461. www.ILADS.org

This editorial by Dr. Lantos was published together with an article by Wressnigg and colleagues from Baxter Bioscience in support of a new Lyme vaccine developed by Baxter Bioscience. Our published Letter to the Editor (http://www.ncbi.nlm.nih.gov/pubmed/24355028/) responded in part to Dr. Lantos.

Both the Baxter Bioscience article and the Lantos editorial make short shrift of patient vaccine safety concerns, which Lantos describes as “largely unsubstantiated”. We note that the previous LYMErix vaccine sparked a class action lawsuit from patients who claimed that they were harmed by the vaccine, which was ultimately pulled from the market by the manufacturer. We also note that "by withdrawing LYMErix when it did, the manufacturer avoided releasing phase 4 post-marketing data that probably would have shown increased side-effects related to the vaccine. The data have never been disclosed."

We conclude that patient trust in new Lyme vaccines will require that legitimate safety concerns regarding the previous vaccine be acknowledged and addressed. Because Lyme vaccines are given to a healthy population, our first priority is to make sure that they are safe.

References

Stricker RB. Lymerix® risks revisited. Microbe 2008;3:1-2.
Smith P, Gaito A, Marks DH. Transcript of FDA Lymerix Meeting, Bethesda, MD, January 22, 2002. Available at: http://www.lymediseaseassociation.org/index.php?option=com_content&view=article&id=532:lymerix-meeting&catid=129:hhsfood-a-drug-administration-fda&Itemid=531
Croke CL, Munson EL, Lovrich SD, et al. Occurrence of severe destructive Lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi. Infect Immun. 2000;68:658–63.
Rose CD, Fawcett PT, Gibney KM. Arthritis following recombinant outer surface protein A vaccination for Lyme disease. J Rheumatol. 2001;28:2555–7.
Latov N, Wu AT, Chin RL, Sander HW, Alaedini A, Brannagan TH. Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi. Periph Nerv Syst. 2004;9:165–7.
Alaedini A, Latov N. Antibodies against OspA epitopes of Borrelia burgdorferi cross-react with neural tissue. J Neuroimmunol. 2005;159:192–5.
Souayah N, Ajroud-Driss S, Sander HW, Brannagan TH, Hays AP, Chin RL. Small fiber neuropathy following vaccination for rabies, varicella or Lyme disease. Vaccine 2009;27:7322-5.
Marks DH. Neurological complications of vaccination with outer surface protein A (OspA). Int J Risk Saf Med. 2011;23:89-96.
Molloy PJ, Berardi VP, Persing DH, Sigal LH. Detection of multiple reactive protein species by immunoblotting after recombinant outer surface protein A Lyme disease vaccination. Clin Infect Dis. 2000;31:42-7.
Fawcett PT, Rose CD, Budd SM, Gibney KM. Effect of immunization with recombinant OspA on serologic tests for Lyme borreliosis. Clin Diagn Lab Immunol. 2001;8:79-84.
Hanson MS, Edelman R. Progress and controversy surrounding vaccines against Lyme disease. Expert Rev Vaccines 2003;2:683–703.
Nigrovic LE, Thompson KM. The Lyme vaccine: a cautionary tale. Epidemiol Infect. 2007;135:1–8.
Nardelli DT, Munson EL, Callister SM, Schell RF. Human Lyme disease vaccines: past and future concerns. Future Microbiol. 2009;4:457-69.
Smith P. Remarks to Vaccines and Related Biological Products Advisory Committee, Bethesda, MD, January 31, 2001. Available at: http://www.lymediseaseassociation.org/index.php?option=com_content&view=article&id=262:vaccine-remarks&catid=80:controversy&Itemid=76

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