Abstract

The Neutralizing Antibody Scientific Research Support Component will provide essential laboratory and scientific support for CHAVI- by performing high throughput assessments of neutralizing activity against tier 1 and tier 2 reference HlV-1 strains in standardized and validated assays. In addition, we will map the epitopes of broadly neutralizing sera and mAbs, monitor vaccine-elicited nAb responses to identify improved immunogens, adjuvants and vectors, and delineate nAbs as a correlate of protection using breakthrough viruses from phase 2b trials.
Specific Aims Aim 1. To support CHAVI-ID research by defining the magnitude and breadth (M-B) of neutralizing activity in sera from select clinical groups, and by mapping the epitopes of broadly neutralizing sera.
Aim 2. To support CHAVI-ID research by screening memory B cell culture supernatants to identify nAb-producing B cells.
Aim 3. To support CHAVI-ID research by characterizing new mAbs for magnitude and breadth of neutralizing activity and epitope specificity.
Aim 4. To support CHAVI-ID research by monitoring the magnitude and breadth of vaccine-elicited nAbs in animals, human vaccinees, and by assessing vaccine sera neutralization with viruses from vaccine breakthrough infections in humans.

Public Health Relevance

Immunogens that elicit broadly cross-reactive neutralizing antibodies may be important for effective vaccination against HlV-1. Vaccines are the most effective and affordable intervention to control the spread of infectious diseases such as AIDS.

  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 #
5UM1AI100645-03
Application #
8681337
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Type
DUNS #
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:

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