The major objective of the studies being proposed is to design HIV-1 envelope antigens that can elicit broadly reactive neutralizing antibodies (Nabs), with a long-term goal of developing a protective vaccine against the virus. We are taking a two-pronged approach of targeting gp41 membrane proximal external region (MPER) and the outer domain of gp120 (gp120OD). We have generated two prototypic antigens based on soluble form of gp41 MPER and gp1200D derived from M group consensus envelope. Both proteins can elicit Nabs against multiple primary HIV-1 isolates in mice. Our goal is to use current and evolving understanding of biochemical, structural and immunogenic properties of the prototypic antigens to design second-generation antigens that could induce even more potent Nabs. To achieve the goal, we have put together a strong, complementary, collaborative team of investigators with expertise in structural biology, virology, protein biochemistry, molecular biology, immunology and vaccinology.
The specific aims of the Project 1 are: (1) to better define B cell epitopes on gp41 MPER, (2) to improve immunogenicity of neutralizing epitopes on gp41 MPER, and (3) to develop and evaluate immunogenicity of antigens based on gp120OD. Successful completion of the proposed studies would represent a major advancement towards developing a protective AIDS vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI074286-05
Application #
8377552
Study Section
Special Emphasis Panel (ZAI1-TJP-A)
Project Start
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$563,547
Indirect Cost
$129,840
Name
Iowa State University
Department
Type
DUNS #
005309844
City
Ames
State
IA
Country
United States
Zip Code
50011
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Qin, Yali; Banerjee, Saikat; Agrawal, Aditi et al. (2015) Characterization of a Large Panel of Rabbit Monoclonal Antibodies against HIV-1 gp120 and Isolation of Novel Neutralizing Antibodies against the V3 Loop. PLoS One 10:e0128823
Habte, Habtom H; Banerjee, Saikat; Shi, Heliang et al. (2015) Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region. Virology 486:187-97
Qin, Yali; Shi, Heliang; Banerjee, Saikat et al. (2014) Detailed characterization of antibody responses against HIV-1 group M consensus gp120 in rabbits. Retrovirology 11:125
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