HIV/AIDS remains a global health problem that needs to be addressed with basic and applied research Methods developed by Dr. Nussenzweig to isolate large numbers of anti-HIV antibodies from the sera of HIV-infected individuals offers the opportunity for comprehensive structural and functional experiments to study the new antibodies using structural biology, in vitro and in vivo characterizations, and studies of effector functions mediated by Fc receptors. Expression and production of purified proteins, including HIV proteins, Fc receptors, and natural and designed antibodies, is a major component of our program project. Dr. Nussenzweig will need large quantities of purified antibodies as well as gp120s and gp140s designed to be potential immunogens for the in vivo studies proposed in Project 1. Dr. Ravetch will need a panel of HAAD and other anti-HIV antibodies with modified Fc regions and altered glycans for evaluating effector functions in Project 2. Dr. Bjorkman will need large quantities of purified Fabs, Fc receptors, and many forms of gpl20 or gpl40 antigens (including resurfaced gpl20s) for complex formation, crystallization, structure determinations, and immunogen studies in Project 3. The large number of different antibodies, HIV proteins, and Fc receptors to be expressed and purified requires a dedicated protein expression core.

Public Health Relevance

Biochemical, structural, and cellular assays to evaluate a new set of anti-HIV antibodies will require expression of large numbers of proteins, including HIV envelope proteins and antibodies. The Protein Expression Core will provide purified proteins for this program project, which will facilitate the goals of understanding how to elicit broadly neutralizing antibodies with enhanced effector functions, and how to improve them for passive immunization.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-RRS-A (J1))
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California Institute of Technology
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West Jr, Anthony P; Scharf, Louise; Scheid, Johannes F et al. (2014) Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell 156:633-48
Klein, Florian; Nogueira, Lilian; Nishimura, Yoshiaki et al. (2014) Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants. J Exp Med 211:2361-72
Halper-Stromberg, Ariel; Lu, Ching-Lan; Klein, Florian et al. (2014) Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell 158:989-99
Bournazos, Stylianos; Klein, Florian; Pietzsch, John et al. (2014) Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell 158:1243-53
Ahmed, Alysia A; Giddens, John; Pincetic, Andrew et al. (2014) Structural characterization of anti-inflammatory immunoglobulin G Fc proteins. J Mol Biol 426:3166-79
Scharf, Louise; Scheid, Johannes F; Lee, Jeong Hyun et al. (2014) Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep 7:785-95
Diskin, Ron; Klein, Florian; Horwitz, Joshua A et al. (2013) Restricting HIV-1 pathways for escape using rationally designed anti-HIV-1 antibodies. J Exp Med 210:1235-49
Shingai, Masashi; Nishimura, Yoshiaki; Klein, Florian et al. (2013) Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 503:277-80
Horwitz, Joshua A; Halper-Stromberg, Ariel; Mouquet, Hugo et al. (2013) HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc Natl Acad Sci U S A 110:16538-43
Chuang, Gwo-Yu; Acharya, Priyamvada; Schmidt, Stephen D et al. (2013) Residue-level prediction of HIV-1 antibody epitopes based on neutralization of diverse viral strains. J Virol 87:10047-58

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