Higgins Hall 414
Telephone: 617-552-3556
Email: ismael.fofana@bc.edu
ORCID
HIV/AIDS vaccine, SIV/macaque model of AIDS, Phage Display and Antibody Engineering, Virus evolution and escape of antibody responses
HIV infection in humans and SIV infection in macaques are accompanied by the development of antibody responses to viral antigens, especially the envelope glycoprotein. In the majority of cases, these antibodies fail to protect and infected subjects eventually progress to AIDS. Similarly, induction of protective antibodies by vaccination remains a daunting enterprise. Antibodies produced in response to viral infection can be classified into neutralizing and non-neutralizing. Neutralizing antibodies are highly desirable but have yet to be achieved by vaccination. Moreover, a number of studies have now suggested a role for non-neutralizing antibodies in preventing infection and/or disease progression. In either case, it often happens that resistant virus strains emerge in infected individuals prior to development of protective antibodies, rendering their presence of no benefit in preventing disease progression. Conventional methods for viral escape variant identification by Sanger sequencing and antibody immune response assessment by ELISA, EliSpot or viral neutralization assay appear insufficient to elucidate the mechanism of protection during the continuous race for survival between virus and host immune responses.
In order to study the interplay between virus and antibody, we use the SIV/macaque model of HIV/AIDS. We assess immune response to vaccination or infection by conventional parameters, such as RNA viral load, antibody titer (ELISA), virus neutralization assay, B cell EliSpot, B cell dysfunction/phenotypes (by multiparameter flow cytometry). We also use high throughput next generation sequencing to track the appearance of virus escape variants and to understand the evolution of immunoglobulin genes (IgG). Finally, we use phage display technology to select viral-specific monoclonal antibodies and genetic engineering to improve neutralizing potency of promising clones.