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Principal Investigator: Pablo Penaloza-MacMaster
Organization: NORTHWESTERN UNIVERSITY AT CHICAGO
Fiscal Year: 2024
Award: $498,659
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY:
Developing a vaccine against HIV is thus a research priority, but it has been difficult in part because vaccines
have not been able to generate sufficient antiviral immunity able to prevent infection. Our prior research using
Ad5-vectored vaccines show that vaccine prime fractionation improves vaccine-elicited immune responses,
especially neutralizing antibody responses. We have shown that a prime with a low dose (LD) of vaccine,
followed by a booster with a standard dose (SD) of vaccine, results in more potent induction of immune
responses, relative to priming and boosting with the same SD. These results with Ad5 beg the question of
whether vaccine fractionation can also improve other vaccine platforms, and whether such initial “micro-dosing”
approach can be utilized to develop more effective HIV vaccines. To answer this question, our proposal will
have 2 Specific Aims:
Specific Aim 1. To evaluate whether vaccine fractionation improves the immunogenicity of Ad26- and
mRNA-based HIV vaccines in mice. Our prior data using an Ad5-SIV vector vaccine show that priming mice
with a LD of vaccine, followed by boosting with a SD of vaccine results in superior immune responses relative to
priming and boosting with the same SD. These data provide a rationale for testing whether the same
immunological effects occur with other HIV/SIV vaccines in mice, including Ad26 and mRNA.
Specific Aim 2. To evaluate the safety, immunogenicity, and efficacy of fractionated HIV vaccines in
macaques. In this aim we will extend our findings to macaques and determine whether vaccine fractionation
improves the immunogenicity and protective efficacy of HIV vaccines.
Our overarching hypothesis is that HIV vaccines can be improved by reducing the priming dose. This
hypothesis is based on our recent published data, as well as a recent vaccine trial (ChAdOx1 nCoV-19) in which
the prime dose was accidentally reduced to half and shown to confer higher protection upon boosting, relative
to standard prime dose upon boosting. Taken together, our studies will provide a framework for developing more
effective vaccines against HIV and other infectious diseases and may warrant a re-evaluation of current vaccine
dosing schemes.
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