Abstract

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).

  Funding Agency

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

  Institution

Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Castillo-Menendez, Luis R; Witt, Kristen; Espy, Nicole et al. (2018) Comparison of Uncleaved and Mature Human Immunodeficiency Virus Membrane Envelope Glycoprotein Trimers. J Virol 92:
Brown, Eric P; Weiner, Joshua A; Lin, Shu et al. (2018) Optimization and qualification of an Fc Array assay for assessments of antibodies against HIV-1/SIV. J Immunol Methods 455:24-33
Finney, Joel; Yeh, Chen-Hao; Kelsoe, Garnett et al. (2018) Germinal center responses to complex antigens. Immunol Rev 284:42-50
Pardi, Norbert; Hogan, Michael J; Naradikian, Martin S et al. (2018) Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med 215:1571-1588
Eudailey, Joshua A; Dennis, Maria L; Parker, Morgan E et al. (2018) Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques. mSphere 3:
Kelsoe, Garnett; Haynes, Barton F (2018) What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling. Cold Spring Harb Perspect Biol 10:
Wagh, Kshitij; Kreider, Edward F; Li, Yingying et al. (2018) Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth. Cell Rep 25:893-908.e7
Fu, Qingshan; Shaik, Md Munan; Cai, Yongfei et al. (2018) Structure of the membrane proximal external region of HIV-1 envelope glycoprotein. Proc Natl Acad Sci U S A 115:E8892-E8899
Fera, Daniela; Lee, Matthew S; Wiehe, Kevin et al. (2018) HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope. Nat Commun 9:1111
McMichael, Andrew J (2018) Is a Human CD8 T-Cell Vaccine Possible, and if So, What Would It Take? Could a CD8+ T-Cell Vaccine Prevent Persistent HIV Infection? Cold Spring Harb Perspect Biol 10:

Showing the most recent 10 out of 261 publications