Science: clinical trials show that antigen competition can destroy the efficacy of HIV vaccine

November 22, 2019 / bioin / - -- many HIV vaccines are designed to produce strong T cell responses T cell responses are associated with a reduced risk of HIV infection in uninfected people and control of virus replication in HIV infected people HIV antigen gag specific T cells are mainly related to post infection control, and HIV antigen env antigen is the target of protective antibody Therefore, HIV vaccine design usually contains these two antigens However, the inclusion of multiple antigens may lead to antigen competition, thus reducing the potential efficacy of the vaccine In a new clinical study, researchers from the United States, Brazil, Peru and Switzerland vaccinated participants only with HIV antigen gag / pol, or with HIV antigen gag / pol and env at the same time, to see if antigen competition interferes with CD4 T cell response They found that when both gag / pol and env were inoculated at the same time, the detected CD4 T cell response to gag / pol was lower, indicating that the inclusion of multiple antigens in the vaccine may prevent the largest T cell response Relevant research results were published in the Journal of Science Translational Medicine on November 20, 2019 The title of the paper is "anti competition in CD4 + T cell responses in a randomized, multicenter, double blind clinical HIV vaccine trial" HIV-1 from J Roberto Trujillo / Wikipedia Specifically, this clinical study, called HVTN 084, is a randomized, multicenter, double-blind, phase 1 clinical trial designed to investigate whether the addition of Env to a gag / pol vaccine reduces the magnitude or breadth of the gag / pol specific T-cell response Fifty volunteers received intramuscular injection of 1 × 10 10 granule unit (PU) of Rad5 gag / pol and enva / B / C (mixed in a ratio of 3:1:1:1) or 5 × 10 9 granule unit of Rad5 gag / pol The CD4 + T cell responses measured by cytokine expression at 4 weeks after vaccination were significantly higher in the non env vaccinated group than in the env vaccinated group, but there was no significant difference in the CD8 + T cell responses between the two vaccinated groups They further revealed that compared with the co immunization of gag / pol and env, in the absence of Env, the response of gag / pol specific T cells was more extensive The addition of Env antigen to gag / pol vaccine resulted in a decrease in the response rate and amplitude of CD4 + T cells against gag / pol, as well as a decrease in the width of antigen epitopes, which confirmed the existence of antigen competition Therefore, the vaccine strategy based on T cell should be aimed at selecting the simplest set of antigens to reduce the interference of single vaccine component to induce the maximum achievable immune response (bio Com) reference: esper g kallas el Antigenic competition in CD4 + T cell responses in a randomized, multicenter, double blind clinical HIV vaccine trial Science Translational Medicine, 2019, DOI: 10.1126/scitranslmed.aaw1673