We propose a Phase I STTR study to develop a novel human immunodeficiency virus (HIV) vaccine strategy with the potential of world-wide efficacy. The HIV/AIDS pandemic remains a major global burden. No test vaccine based on traditional scientific principles has induced sufficiently protective immunity to HIV. Induction of neutralizing antibodies (Abs), the cornerstone of vaccination against microbes, has been thwarted by: (a) mutability of the immunodominant viral epitopes, and (b) poor adaptive immunological response to conserved epitopes important in virus-host cell interactions. CD4 binding by the HIV envelope glycoprotein gp120 is an obligatory step in the HIV life cycle. gp120 residues 421-433 constitute the mostly-conserved core of the CD4 binding site (CD4BScore). Except for rare survivors of prolonged HIV infection, the immune system does not support the production of anti-CD4BScore Abs. The proposed Phase I project focuses on electrophilic immunogens (E-immunogens) derived from the novel chemical engineering strategy termed "Covalent Vaccination" concept. E-immunogens hold the potential of inducing the synthesis of protective Abs that is beyond the scope of the physiological immune response. We will carry out the following developmental studies: (i) Characterize and compare the protective anti-HIV properties of rabbit and mouse antibodies raised by immunization with electrophilic derivatives of purified gp120 and synthetic 416-433 peptide;(ii) Maximize the antibody response to the lead E-immunogen using alternate adjuvants. Proving preclinical proof-of-principle for covalent vaccination as an effective approach in the present project is an important step in translating this approach for HIV vaccination.

Public Health Relevance

This project is directed toward developing a novel vaccine strategy for HIV infection. If the strategy is proven valid, the project holds the potential of contributing a candidate HIV vaccine suitable for advanced preclinical studies and commercial development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
5R41AI093261-02
Application #
8322038
Study Section
HIV/AIDS Vaccines Study Section (VACC)
Program Officer
Lane, Jim R
Project Start
2011-09-01
Project End
2014-06-30
Budget Start
2012-09-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$300,000
Indirect Cost
Name
Covalent Bioscience, Inc.
Department
Type
DUNS #
965999738
City
Houston
State
TX
Country
United States
Zip Code
77054