Viral Immunology

Viral Immunology
Phone: (212) 570-3058
Email: sjiang@nybloodcenter.org

LABORATORY OBJECTIVES
1. Rational design and identification of HIV entry inhibitors targeting gp41.
2. Structure and function of the HIV-1: Implication for designing anti-HIV vaccines.
3. Identification and development of microbicides for preventing sexual transmission of HIV.
4. Development of therapeutics, immunotherapeutics and subunit vaccines against SARS-CoV.
5. Development of therapeutics, antibodies and vaccines against influenza viruses.
6. Development of protein-based adjuvants.

The Laboratory of Viral Immunology, headed by Shibo Jiang, M.D, Ph.D., has focused on development of therapeutics and vaccines for treatment and prevention of HIV infection/AIDS and other emerging infectious diseases caused by viruses with type 1 viral fusion proteins, such as severe acute respiratory syndrome associated coronavirus (SARS-CoV) and influenza viruses.

In early 1990s, Dr. Jiang and colleagues discovered the first anti-HIV peptide derived from the HIV-1 gp41 C-terminal heptad repeat region. The patents on this discovery were licensed to Trimeris Inc., a pharmaceutical company which, in partnership with F. Hoffmann-La Roche Ltd., has developed a peptidic anti-HIV drug, Fuzeon. This drug was licensed by the US FDA in 2003 as the first member of a new class of anti-HIV drugs, HIV fusion inhibitors, for treatment of HIV/AIDS patients who have failed to respond to the current antiretroviral therapeutics. Dr. Jiang's group, in collaboration with Dr. Asim K. Debnath, has developed a series of high throughput screening assays and identified a series of small molecule "drug-like" compounds with potent HIV fusion inhibitory activity. These active compounds will be used as leads for optimization in order to design novel small molecule HIV fusion inhibitors as new anti-HIV drugs. Dr. Jiang's group has demonstrated that T20 has multiple binding sites in gp41 and gp120, which will be used as new targets for designing anti-HIV compounds and vaccines.

Sexual transmission is the major route of HIV spread. Development of effective and safe anti-HIV microbicides is urgently needed for prevention of sexual transmission of HIV. Dr. Jiang's group has screened thousands of small molecule compounds, pharmaceutical excipients, and chemically modified proteins, resulting in identification of a number of anti-HIV microbicide candidates, e.g., meso-tetra (4-carboxyphenyl) porphine (MTCPP), 3-hydroxyphthaloyl-β-lactoglobulin (3HP-β-LG), and cellulose acetate 1,2-benzene-dicarboxylate (CAP). These microbicide candidates have been tested for the in vitro anti-HIV activity against both cell-free and cell-associated laboratory-adapted and primary HIV-1 strains with distinct genotypes and phenotypes. Dr. Jiang's group has also demonstrated that combinations of CAP with reverse transcriptase inhibitors (e.g., UC781 and TMC 120) have significant synergistic and complementary effects against HIV.

Discovery of anti-HIV peptides has opened a new avenue for development of antiviral drugs and vaccines for treatment and prevention of other emerging infectious diseases caused by viruses with type 1 viral fusion proteins, such as Ebola virus, influenza virus, paramyxoviruses, and SARS-CoV, etc. Using similar approaches, Dr. Jiang's group has identified anti-SARS-CoV peptides, and found that the receptor-binding domain (RBD) in SARS-CoV S protein can induce highly potent neutralizing polyclonal and monoclonal antibodies. These peptides and antibodies can be used for urgent treatment and prophylaxis of SARS. The RBD proteins will be further developed as safe and effective vaccines for preventing SARS outbreaks in the future. Dr. Jiang's laboratory will also use the similar approaches to develop antiviral drugs and vaccines against other emerging diseases caused by viruses with type 1 viral fusion proteins for biodefense preparedness.