Assaying Potency of Novel Vaccines
October 11-12, 2005
NIH Natcher, Bethesda, MD
The purpose of the "Assaying Potency of Novel Vaccines" workshop was to develop consensus regarding several scientific questions and identify research gaps that preclude consensus being reached on these questions and others identified during the conference/workshop. The workshop was co-organized by three NIAID components -- the Division of AIDS (DAIDS), the Vaccine Research Center, and the Division of Microbiology and Infectious Diseases (DMID) -- and by the International AIDS Vaccine Initiative, FDA/Center for Biologics Evaluation and Research, and the World Health Organization (WHO). Funding was provided by DAIDS, DMID, WHO, and the Office of AIDS Research.
For HIV/AIDS, tuberculosis, and malaria, immune correlates of protection are not anticipated to be identified until after completion of efficacy trials with effective, even if partially effective, vaccine candidates. Even then, a correlate of protection may not be discovered. Hence, the development of appropriate potency assays for HIV/AIDS and malaria, for which no effective vaccines currently exist, and for tuberculosis, for which there is an existing vaccine of only controversial effectiveness, presents unique challenges.
Nevertheless, validated potency tests will be needed to release the lots of vaccines to be used in pivotal Phase III efficacy trials, for consistency lot studies, and potentially, for bridging studies. Vaccine potency is generally determined by measuring quantitative responses in a bioassay relevant to the mode of action of the vaccine. In other words, to demonstrate that each lot of vaccine generates the immune correlate of protection of sufficient quality and quantity in an appropriate animal model or in the case of live viruses, by measuring the viral titer to demonstrate that each lot of vaccine can replicate to levels associated with immune protection. In addition, potency assays need to be suitably quantitative. Potency determination for novel HIV/AIDS, tuberculosis, and malaria vaccines will be challenging for the following reasons. In addition to the immune correlates of protection being unknown, vector titer may or may not correlate with insert expression, and vector titer/expression levels of recombinant antigens may or may not correlate with immunogenicity. In addition, determining potency for each lot of the components of a vaccine heterologous prime-boost regimen constitutes an unique challenge.
Despite these challenges, potency tests to support advancement of candidates into upcoming Phase III trials for HIV/AIDS, malaria, tuberculosis, and other vaccines will need to be developed and validated as soon as possible and a rational path forward to doing so needs to be discussed.
List of meeting presentations
If you would like to receive a copy of any of the presentations, please contact Rebecca Sheets at rsheets@niaid.nih.gov.
Scientific Steering Committee:
NIAID: Rebecca Sheets (Chair)
DAIDS: Stuart Shapiro, Chris Butler
DMID: Nick Obiri, Christine Sizemore
VRC: Rick Koup
IAVI: Vera Byrnes
WHO: Saladin Osmanov
FDA/CBER: Hana Golding, Lev Sirota
Academia: Harriet Robinson, Emory Univ.
Industry: John Lewis, formerly of Merck
Session chairs:
Session 1 and Round-table Discussion: Lewellys Barker, Aeres
Session 2: Henry Hsu, FDA/CBER, Tim Schofield, Merck
Session 3: Keith Peden, FDA/CBER, Lee Hall, DMID
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