The Immunogen Production and Immunizations Core (Core B) will support activities in all three Projects of this HIVRAD application. Specifically many of the reagents and assays that support the activities of all three Projects have been consolidated in this Core. In addition, all animal-related activities have been consolidated in this Core. Studies in nonhuman primates (rhesus macaques) will be conducted in the Washington National Primate Research Center (WaNPRC). The WaNPRC will provide comprehensive, efficient and safe conduct of the nonhuman primate-related portions of the HIVRAD Program including animal selection, research protocol implementation and execution, sample acquisition and distribution, animal care, and project budget administration. Immunizations of rabbits and mice will be performed under a 'fee-for-service'agreement with Pocono Rabbit Farm and Laboratory Inc. Hybridoma generation will be performed at Viro Dynamics, under a 'fee-for-service'agreement. Sera and monoclonal antibodies from the immunized animals will be analyzed for specificity and neutralizing activity.

Public Health Relevance

Identifying immunogens and immunization protocols for the optimal simulation of B cells to generate neutralizing antibodies against HIV, is crucial for the development of an effective vaccine against this virus. The studies in this proposal aim at providing key information on the intracellular events that follow the recognition of immunogens by B cells and which events lead to the production of protective anti-HIV antibody responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI094419-02
Application #
8375324
Study Section
Special Emphasis Panel (ZAI1-BP-A)
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$642,380
Indirect Cost
$211,353
Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
070967955
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Dosenovic, Pia; von Boehmer, Lotta; Escolano, Amelia et al. (2015) Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice. Cell 161:1505-15
McGuire, Andrew T; Glenn, Jolene A; Lippy, Adriana et al. (2014) Diverse recombinant HIV-1 Envs fail to activate B cells expressing the germline B cell receptors of the broadly neutralizing anti-HIV-1 antibodies PG9 and 447-52D. J Virol 88:2645-57
McGuire, Andrew T; Dreyer, Anita M; Carbonetti, Sara et al. (2014) HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. Science 346:1380-3
Finton, Kathryn A K; Friend, Della; Jaffe, James et al. (2014) Ontogeny of recognition specificity and functionality for the broadly neutralizing anti-HIV antibody 4E10. PLoS Pathog 10:e1004403

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