Ronald Desrosiers, PhD
Department of Microbiology and Molecular Genetics, Harvard Medical SchoolDirector, The New England Primate Research Center
HIV and AIDS: vaccine; persistent immune response
Develop new strategies for blunting viral replication and bolstering the immune system’s ability to eradicate viral-infected T-cell reservoirs.
Develop potent, yet less toxic, therapies for those living with HIV infection, and develop a vaccine to ameliorate the spread of new HIV infections.
Twenty-five years after the identification of HIV, the agent responsible for causing AIDS, the outlook for stemming the spread of infection remains bleak. The prevalence of HIV infections and AIDS have reached pandemic proportions, and is a global health catastrophe. Current treatments do not eradicate the virus, are not preventative for future infection, and have significant side effects. Consequently, there is an enormous need for improved therapies, as well as a “magic bullet”; that is, a vaccine that can confer long-lasting immune protection to those uninfected. The non-human primate studies on SIV infection and vaccine development in Dr. Desrosiers’ laboratory represent one of the most promising avenues for developing potent, yet less toxic, therapies for those living with HIV infection, as well as a vaccine to ameliorate the spread of new infections. Industry collaborations can expedite these important research initiatives, and help devise new treatment options. Moreover, the lab has unique resources and expertise (for example, recombinant viral vectors and viral-encoded genes) that may have great value.
Current Research Interests
There is a growing realization that an effective vaccine against HIV infection may take decades to develop, due in large part to the virus' ability for mutating its genetic information when confronted with an antagonist. Consequently, studying SIV infection may be the optimal surrogate approach for studying HIV biology, and Dr. Desrosier's lab is a leader in this field. The lab is currently:
- Exploring novel methods for producing a stable protective immune response to counter the persistent infection characteristic of SIV/HIV.
- Continuing investigating new approaches for vaccine development, including the potential of novel, genetically-engineered, viral vectors, such as recombinant herpes viruses, for inciting long-lasting antiviral immune responses.
- Analyzing the structure-function relationships of SIV-encoded proteins in the context of infectivity and neutralization, with the goal of identifying the virus’ Achilles heel.
- Exploring combination modalities and genetic therapy approaches for constraining viral pathogenesis.
- Employing rhesus monkey B-lymphocyte culture systems to study latent infection, replication, and infection sustainability of rhesus monkey rhadinovirus, the counterpart to human herpesvirus 8/KSHV.
- Utilizing a cosmid-based, genetically engineered RRV to compare infectivity and neutralization in fibroblasts, which accommodate lytic infection and B-lymphocytes.
Dr. Desrosiers’ laboratory is world renowned for its research on human immunodeficiency virus (HIV) and its close relative simian immunodeficiency virus (SIV), two members of the lentivirus subfamily of retroviruses. The lab has made important contributions to the understanding of vaccine development, viral pathogenesis, and the function of viral-encoded proteins. The lab discovered SIV, as well as the rhesus monkey rhadinovirus (RRV), which resembles human herpesvirus-8. The identification of SIV in non-human primates has paved the way for modeling AIDS and for performing molecular analysis of SIV pathogenesis. The lab performed groundbreaking vaccine studies in monkeys that demonstrated the feasibility of developing a vaccine against HIV infection, by employing a live, attenuated version of SIV devoid of a critical gene.
Although HIV vaccination still remains an elusive goal, the lab has continued to explore novel ways to generate protective immunity. Moreover, the lab’s investigations revealed important insights into the ability of SIV to elicit persistent infection that results in a catastrophic disease course, similar to its human counterpart, HIV. The lab’s studies have also uncovered important molecular aspects of the SIV-encoded envelope glycoprotein (that is, env gene) and gag genes, including correlating structural features of the env gene to infectivity and neutralization of SIV. They have recently demonstrated that disruption of the V1 variable loop can lead to virus neutralization sensitivity.