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.

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
Name
Duke University
Department
Type
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
Bonsignori, Mattia; Scott, Eric; Wiehe, Kevin et al. (2018) Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity 49:1162-1174.e8
Blasi, Maria; Negri, Donatella; LaBranche, Celia et al. (2018) IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells. Commun Biol 1:134
Song, Hongshuo; Giorgi, Elena E; Ganusov, Vitaly V et al. (2018) Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection. Nat Commun 9:1928
Hurwitz, Julia L; Bonsignori, Mattia (2018) Multi-Envelope HIV-1 Vaccine Development: Two Targeted Immune Pathways, One Desired Protective Outcome. Viral Immunol 31:124-132
Yates, Nicole L; deCamp, Allan C; Korber, Bette T et al. (2018) HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J Virol 92:
Castillo-Menendez, Luis R; Nguyen, Hanh T; Sodroski, Joseph (2018) Conformational Differences Between Functional Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Trimers and Stabilized Soluble Trimers. J Virol :
Finney, Joel; Kelsoe, Garnett (2018) Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design. Retrovirology 15:53
Bradley, Todd; Peppa, Dimitra; Pedroza-Pacheco, Isabela et al. (2018) RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses. Cell 175:387-399.e17
Richard, Jonathan; Prévost, Jérémie; Baxter, Amy E et al. (2018) Uninfected Bystander Cells Impact the Measurement of HIV-Specific Antibody-Dependent Cellular Cytotoxicity Responses. MBio 9:
Pardi, Norbert; Hogan, Michael J; Porter, Frederick W et al. (2018) mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov 17:261-279

Showing the most recent 10 out of 261 publications