Dr. Michael Cho, Co-Director
Dr. Michael Cho, PhD
The primary focus of my laboratory is development of a vaccine against human immunodeficiency virus (HIV-1), the virus that causes AIDS. In connection with this research, we characterize biochemical and immunological properties of viral envelope glycoprotein, develop and evaluate novel vaccine vectors, and examine virus-host interactions at various levels.
AIDS pandemic has already resulted in the deaths of millions of lives and there are now over 40 million people estimated to be infected with HIV-1 worldwide. Development of a vaccine against HIV-1 is an important goal in a battle against AIDS. One of the major obstacles in developing an effective vaccine against the virus is the inability to elicit neutralizing antibodies (Nabs) that are broadly reactive against the large number of HIV-1 isolates that exist. The high degree of genetic variation of viral envelope glycoprotein (viz. gp120) is the primary reason for the difficulty in inducing broadly reactive Nabs. Extensive glycosylation and complex structure of the protein also contribute. Hence, one of our goals is to better understand the biochemical and immunological properties of gp120.
In the past few years, we have developed a vaccine candidate that can induce strong protective immune responses in macaques against a highly pathogenic SHIV (chimeric virus generated between HIV-1 and SIV); vaccinated animals are able to control viral replication, maintain normal levels of CD4+ T cells, and remain healthy. This vaccine is based on recombinant vaccinia virus vector-prime/subunit protein-boost regimen and elicits immunity against viral proteins Gag, Pol and Env. Our future goal is to improve this vaccine regimen by developing novel vaccine vectors (DNA- or virus-based) and targeting additional HIV-1 proteins (e.g. Tat, Rev and Nef).
Also, in response to national need in biodefense, we have recently initiated vaccine projects against a number of potential agents of bioterrorism.
Penn-Nicholson, A., D. P. Han, S. J. Kim, H. Park, R. Ansari, D. C. Montefiori, and M. W. Cho (2008). Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope. Virology. 372: 442-56. [PubMed]
D. P. Han, M. Lohani and M. W. Cho (2007). Specific asparagine-linked glycosylation sites are critical for DC-SIGN- and L-SIGN-mediated SARS-CoV entry. J. Virol. 81:12029-12039. [PubMed]
Han, D. P., A. Penn-Nicholson and M. W. Cho (2006). Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor. Virology. 350: 15-25. (Cover illustration). [PubMed]
Cho, M. W. (2003) Subunit protein vaccines: Theoretical and practical considerations for HIV-1. Current Mol. [PubMed]
Kim, Y. B., D. P. Han, C. Cao, M.W. Cho (2003). Immunogenicity and ability of variable loop-deleted human immunodeficiency virus type 1 envelope glycoproteins to elicit neutralizing antibodies. Virology. 305: 124-137. [PubMed]