In June 2012, the DHVI was awarded a grant by the CAVD to develop dimeric IgA human monoclonal antibodies as passive therapy for HIV-1 prevention. In the follow-up analysis of the RV144 HIV trial, IgA antibodies were induced in plasma and could capture HIV-1 virions; however, monomeric plasma IgA was identified as a correlate of risk for HIV infection. During HIV infection, this type of antibody potentially blocks the effector functions of IgG antibodies, which confer protection against HIV. Therefore, Haynes and colleagues hypothesized that the induction of dimeric and secretory IgA could prevent virus transmission.
Through the support of this grant, DHVI investigators will develop the enabling technology for the expression and testing of these antibodies to determine their ability to protect against HIV transmission in vitro and in vivo. Preclinical passive protection studies will be conducted in non-human primates to determine the roles of these antibodies as correlates of protection from the simian/human immunodeficiency virus. In addition, therapeutic human dimeric IgA will be developed as a preventive therapy in vivo.