The rationally-designed immunogens developed in Projects 1 and 2 and produced in Core B will be tested in vivo in this Core for their ability to induce Abs in rabbits and/or non-human primates that are broadly reactive against HIV-1 isolates of different clades. The experiments will utilize an established DNA prime/protein boost protocol in which the DNA priming constructs will include Env genes, and the boosting constructs will consist of the V2-scaffold immunogen(s) and/or the QNE-scaffold immunogen(s). The work in Core C is divided into two specific aims:
Aim 1. To induce broad, potent, and long-lasting functional Ab responses in rabbits using rationally designed V2-scaffold immunogens as protein boosts subsequent to priming with Env genes. V2/V3 QNE-scaffold immunogens can only be tested in non-human primates because a) rabbits have not been shown to produce Abs carrying CDR H3 regions of the length needed for QNE-specific Abs, and b) it is not know if rabbits possess the immunoglobulin genes required to encode these Abs, whereas we have shown that SHIV-infected NHPs can produce QNE Abs. Thus, the V2/V3 QNE-scaffold immunogens will be tested in NHPs. In contrast, the V2-scaffold immunogens will first be tested in rabbits. To qualify for testing in NHPs, the V2-specific Ab responses achieved in rabbits will need to meet one or more of the following criteria: (a) Induction of Abs that neutralize the majority of Tier 1 pseudoviruses in the assay with titers better than 1:50;(b) Induction of Abs that neutralize >25% of Tier 2 pseudoviruses from at least two clades with titers better than 1:20 in at least one of the three neutralization assays used;(c) Induction of Abs that mediate additional anti-viral functions, and/or display neutralizing or other anti-viral activities against SHIVSFI62P3- Aim 2. To induce broad, potent, long-lasting and protective Ab responses in non-human primates using rationally designed V2- and/or V2/V3 QNEscaffold immunogens as protein boosts subsequent to priming with Env genes.

Public Health Relevance

Experiments performed by this Animal Studies Core C are essential to the success of the entire HIVRAD, as animal testing will be performed in this Core to identify which immunogens and immunization protocols are best able to induce antibodies and protect against infection with HIV-1 in vivo.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
New York
United States
Zip Code
Zolla-Pazner, Susan (2014) A critical question for HIV vaccine development: which antibodies to induce? Science 345:167-8
Zolla-Pazner, Susan; deCamp, Allan; Gilbert, Peter B et al. (2014) Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PLoS One 9:e87572
Evering, Teresa H; Kamau, Edwin; St Bernard, Leslie et al. (2014) Single genome analysis reveals genetic characteristics of Neuroadaptation across HIV-1 envelope. Retrovirology 11:65
Dutta, Moumita; Liu, Jun; Roux, Kenneth H et al. (2014) Visualization of retroviral envelope spikes in complex with the V3 loop antibody 447-52D on intact viruses by cryo-electron tomography. J Virol 88:12265-75
Spurrier, Brett; Sampson, Jared; Gorny, Miroslaw K et al. (2014) Functional implications of the binding mode of a human conformation-dependent V2 monoclonal antibody against HIV. J Virol 88:4100-12
Upadhyay, Chitra; Mayr, Luzia M; Zhang, Jing et al. (2014) Distinct mechanisms regulate exposure of neutralizing epitopes in the V2 and V3 loops of HIV-1 envelope. J Virol 88:12853-65
Mayr, Luzia M; Cohen, Sandra; Spurrier, Brett et al. (2013) Epitope mapping of conformational V2-specific anti-HIV human monoclonal antibodies reveals an immunodominant site in V2. PLoS One 8:e70859
Pan, Ruimin; Sampson, Jared M; Chen, Yuxin et al. (2013) Rabbit anti-HIV-1 monoclonal antibodies raised by immunization can mimic the antigen-binding modes of antibodies derived from HIV-1-infected humans. J Virol 87:10221-31