The major goal of this project is to develop broadly reactive and potent human and rhesus monkey monoclonal antibodies (HMAbs and RhMAbs) recognizing quaternary neutralization epitopes (QNE). This group of epitopes has only very recently received attention, mainly because suitable methods for detecting such antibodies were not previously available. It is now feasible to identify patients whose sera contain this novel class of antibody. MAbs reflecting immune responses to QNEs will be required to precisely define their structure(s). In this project, we will use improved methodologies generating human and rhesus MAbs recognizing QNEs that will contribute critically important reagents for understanding QNE structure and function. Human studies will involve CAPRISA cohort patients, such as CAP256, a South African patient with high titers against QNEs of subtype C isolates, as well as U.S. patients studied in the Pinter lab. Likewise, we will produce monkey MAbs from macaques making QNE directed antibodies as a result of infection with SHIVs expressing conserved VIA/2 determinants of QNEs. MAbs will be used in mapping epitopes and structural analysis of QNEs. This project will involve intense collaborative interactions with all the individual Projects and Cores.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI088610-04
Application #
8429452
Study Section
Special Emphasis Panel (ZAI1-RB-A)
Project Start
Project End
2013-06-30
Budget Start
2013-03-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$32,983
Indirect Cost
$5,445
Name
University of Medicine & Dentistry of NJ
Department
Type
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
Wibmer, Constantinos Kurt; Moore, Penny L; Morris, Lynn (2015) HIV broadly neutralizing antibody targets. Curr Opin HIV AIDS 10:135-43
Moore, Penny L; Williamson, Carolyn; Morris, Lynn (2015) Virological features associated with the development of broadly neutralizing antibodies to HIV-1. Trends Microbiol 23:204-11
Sheward, Daniel J; Ntale, Roman; Garrett, Nigel J et al. (2015) HIV-1 Superinfection Resembles Primary Infection. J Infect Dis 212:904-8
Derdeyn, Cynthia A; Moore, Penny L; Morris, Lynn (2014) Development of broadly neutralizing antibodies from autologous neutralizing antibody responses in HIV infection. Curr Opin HIV AIDS 9:210-6
Salomon, Aidy; Krachmarov, Chavdar; Lai, Zhong et al. (2014) Specific sequences commonly found in the V3 domain of HIV-1 subtype C isolates affect the overall conformation of native Env and induce a neutralization-resistant phenotype independent of V1/V2 masking. Virology 448:363-74
Wibmer, Constantinos Kurt; Bhiman, Jinal N; Gray, Elin S et al. (2013) Viral escape from HIV-1 neutralizing antibodies drives increased plasma neutralization breadth through sequential recognition of multiple epitopes and immunotypes. PLoS Pathog 9:e1003738
Sethi, Anurag; Tian, Jianhui; Derdeyn, Cynthia A et al. (2013) A mechanistic understanding of allosteric immune escape pathways in the HIV-1 envelope glycoprotein. PLoS Comput Biol 9:e1003046
Murphy, Megan K; Yue, Ling; Pan, Ruimin et al. (2013) Viral escape from neutralizing antibodies in early subtype A HIV-1 infection drives an increase in autologous neutralization breadth. PLoS Pathog 9:e1003173
Moore, Penny L; Sheward, Daniel; Nonyane, Molati et al. (2013) Multiple pathways of escape from HIV broadly cross-neutralizing V2-dependent antibodies. J Virol 87:4882-94
Moore, Penny L; Gray, Elin S; Wibmer, C Kurt et al. (2012) Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape. Nat Med 18:1688-92

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