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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI100148-02
Application #
8617126
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
DUNS #
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Bournazos, Stylianos; Wang, Taia T; Dahan, Rony et al. (2017) Signaling by Antibodies: Recent Progress. Annu Rev Immunol 35:285-311
Halper-Stromberg, Ariel; Nussenzweig, Michel C (2016) Towards HIV-1 remission: potential roles for broadly neutralizing antibodies. J Clin Invest 126:415-23
McGuire, Andrew T; Gray, Matthew D; Dosenovic, Pia et al. (2016) Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat Commun 7:10618
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