Trimeric HIV-1 gp140 fused with APRIL, BAFF, and CD40L on the mucosal gp140-specific antibody responses in mice.

Trimeric HIV-1 gp140 fused with APRIL, BAFF, and CD40L on the mucosal gp140-specific antibody responses in mice. Vaccine. 2020 Jan 31;: Authors: Liu J, Clayton K, Gao W, Li Y, Zealey C, Budylowski P, Schwartz J, Yue FY, Bie Y, Rini J, Ostrowski M Abstract HIV-1 envelope (Env)-specific antibody present at mucosal surfaces can block entry of HIV-1 into these portals and thus should be elicited by an HIV-1 preventive vaccine. Since three molecules of tumor necrosis factor superfamily (TNFSF), APRIL, BAFF, and CD40L, could promote mucosal antibody responses, we made fusion constructs of them with an HIV-1 gp140 trimer and tested the mucosal gp140-specific antibody elicited by the fusion constructs in mice using a DNA prime-protein boost vaccination regimen. The fusion constructs formed trimers and displayed both broadly neutralizing antibody epitopes and non-broadly neutralizing antibody epitopes. Compared with the control construct, trimeric gp140, trimeric gp140-APRIL and gp140-BAFF fusion proteins mildly promoted B cell proliferation in vitro, enhanced HIV-1 gp140-binding IgG responses in vaginal lavage or fecal pellets, respectively, and decreased HIV-1 gp140-binding IgA in sera. Gp140-APRIL also augmented HIV-1 gp140-binding IgG in sera. Surprisingly, gp140-CD40L did not promote B cell proliferation in vitro and inhibited mucosal and systemic HIV-1 gp140-binding IgG or IgA. These results suggest that APRIL and BAFF should be further...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research