HARVARD AIDS INSTITUTE SCIENTISTS FORGE TWO FIRSTS IN HIV VACCINE RESEARCH

For immediate release: June 22, 2001

Construction and Analysis of an Infection Human Immunodeficiency Virus Type 1 Subtype C Molecular Clone by Thumbi Ndung'u, Boris Renjifo, and Max Essex Appears in Journal of Virology, Vol. 75. No. 11, June 2001, p. 4964-4972. SHIV abstract has been submitted for publication

Boston—Scientists at HAI have developed the first infectious molecular clone of the strain of HIV-1 subtype C found in Africa and have generated the first Simian/Human Immunodeficiency Virus (SHIV) chimera based on HIV-1C of African origin, providing two critical steps in designing effective vaccine candidates to stop the spread of AIDS. Their paper "Construction and Analysis of an Infectious Human Immunodeficency Virus Type 1 Subtype C Molecular Clone" is published in the June issue of Journal of Virology.

Until now, only one infectious molecular clone of HIV-1C had been constructed from an isolate in India. HAI scientists have developed the first infectious molecular clone of HIV-1C from an isolate in Africa, which is crucial in examining the genetic characteristics of this subtype and understanding its ability to spread so rapidly in the populations of sub–Saharan Africa. The genetic information contained in this molecular clone will act as a live blueprint allowing Institute scientists to introduce mutations to the genome and examine changes in its biologic activity, such as the ability to infect different cell types.

"Our infectious molecular clone is a major development," said Thumbi Ndung’u, research associate at HAI. "In the past, scientists obtained viral isolates from HIV-infected cells to determine a particular effect of the virus but it was difficult to differentiate the specific part of the virus actually producing the effect. An infectious molecular clone, on the other hand, allows us to take apart the virus and understand the contribution of each of its specific building blocks. This development also allows us to understand in fine detail the immune responses to the virus, which is critical for developing new HIV-1 vaccine strategies."

To further facilitate studies on HIV-1C, Institute researchers have also generated the first SHIV chimera for HIV-1C from an African virus isolate. A SHIV is a genetically engineered virus composed of an HIV outer surface and a SIV core. This SHIV will facilitate evaluation in rhesus monkeys of HIV-based envelope vaccines for subtype C. If a vaccine displays promising immune responses in animal models, the vaccine may be considered a candidate for human trials.

"We have long known that vaccines need to be tailored for specific viral strains," says Max Essex, chair of HAI. "Focusing our work on HIV-1C has allowed us to examine why this subtype appears to replicate and mutate far faster than any other HIV subtypes. Understanding the molecular components of this subtype is critical."

Until now, most HIV vaccine research has focused of HIV-1B, the viral subtype found mostly in the world’s developed nations. The prevalence of subtype C, which is now responsible for more than half of the world’s HIV infections, suggests that it may be more infectious (or transmissible per sexual exposure) than other subtypes of HIV-1.

HAI is dedicated to conducting and catalyzing international research to end the worldwide AIDS epidemic.