The primary goal of this Mucosal Biology Scientific Research Support Component (SRSC) is to identify antibody effector functions at mucosal surfaces required to prevent HIV-1 acquisition, define how they differ by route of transmission, and through integrated studies across SRSCs (Mucosal, Vector, Non-human Primate) determine modes of protective antibody induction in non-human primates and in collaborative human clinical vaccine studies.
Specific Aims Aim 1. To support CHAVI-ID by defining the functional nature of protective antibody responses at mucosal surfaces elicited in RV144 follow-on trials (RV306, RV328), in other HlV-1 vaccine trials (HVTN 204, 082, 076) and in the HVTN/CHAVI501 mosaic trial.
Aim 2. To support CHAVI-ID by assessing the functional characteristics of protective antibodies at mucosal surfaces in NHP Core studies designed to determine optimal route/adjuvant combinations for the induction of mucosal immunity.
Aim 3. To support CHAVI-ID by evaluating the functional characteristics of protective antibodies at mucosal surfaces in NHP and Vector SRSC studies designed to determine optimal vector strategies for the induction of mucosal immunity.
Aim 4. To support CHAVI-ID by determining the impact of dimeric vs monomeric antibodies on mucosal acquisition.

Public Health Relevance

The primary goal of this project is to identify the most effective components of vaccine induced responses at mucosal surfaces (vagina, rectum and penis) required to prevent HIV infection and to develop vaccine strategies that will induce and maintain such responses for a prolonged period (years).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1AI100645-02
Application #
8508877
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$251,421
Indirect Cost
$52,070
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Chen, Jia; Frey, Gary; Peng, Hanqin et al. (2014) Mechanism of HIV-1 neutralization by antibodies targeting a membrane-proximal region of gp41. J Virol 88:1249-58
Hraber, Peter; Seaman, Michael S; Bailer, Robert T et al. (2014) Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS 28:163-9
Pollara, Justin; Bonsignori, Mattia; Moody, M Anthony et al. (2014) HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities. J Virol 88:7715-26
Verkoczy, Laurent; Diaz, Marilyn (2014) Autoreactivity in HIV-1 broadly neutralizing antibodies: implications for their function and induction by vaccination. Curr Opin HIV AIDS 9:224-34
Hwang, Kwan-Ki; Trama, Ashley M; Kozink, Daniel M et al. (2014) IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria. PLoS One 9:e90725
Haynes, Barton F; Moody, M Anthony; Alam, Munir et al. (2014) Progress in HIV-1 vaccine development. J Allergy Clin Immunol 134:3-10; quiz 11
Holl, T Matt; Yang, Guang; Kuraoka, Masayuki et al. (2014) Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes. J Immunol 192:3269-79
Roederer, Mario; Keele, Brandon F; Schmidt, Stephen D et al. (2014) Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV. Nature 505:502-8
Dennison, S Moses; Anasti, Kara M; Jaeger, Frederick H et al. (2014) Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide. J Virol 88:9406-17
Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F et al. (2014) Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains. Proc Natl Acad Sci U S A 111:10275-80

Showing the most recent 10 out of 48 publications