希金斯414号厅
电话:617-552-3556
电子邮件: ismael.fofana@misawa-city.com
ORCID 0000-0001-6384-2836
艾滋病毒/艾滋病疫苗, 艾滋病SIV/猕猴模型, Phage Display and Antibody 工程, 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. 在大多数情况下, 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. 此外, a number of studies have now suggested a role for non-neutralizing antibodies in preventing infection and/or disease progression. 无论哪种情况, 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, 比如RNA病毒载量, 抗体效价(ELISA), 病毒中和试验, B细胞elisa试剂盒, 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). 最后, we use phage display technology to select viral-specific monoclonal antibodies and genetic engineering to improve neutralizing potency of promising clones.