Beta7-integrin independent enhancement of mucosal and systemic anti-HIV antibody responses following combined mucosal and systemic gene delivery (41.1)

Abstract

Abstract Vaccination strategies that can block or limit heterosexual HIV transmissions to local and systemic tissues are much sought for. Herein, in a mouse model, we aimed to determine whether the enhancement of antibody responses through mucosal and systemic immunizations, previously observed with protein-based vaccines, applies to immunizations with DNA- or RNA-based vectors. Intra-nasal (i.n.) followed by intra-muscular (i.m.) immunizations (i.n./i.m.) with PLG-DNA microparticles encoding HIV-gag (PLG-DNA-gag) significantly enhanced serum antibody responses, compared i.m., i.n. or i.m. followed by i.n. (i.m./i.n.), immunizations. Moreover, while i.n./i.m., i.n. or i.m./i.n. immunizations with PLG-DNA-gag resulted in genital tract antibody responses, i.m. immunizations alone failed to do so. Importantly, β7-deficient mice developed local and systemic antibody responses following i.n./i.m., or any other routes of immunization similar to wild type mice. To compare the DNA with an RNA delivery system, immunizations were performed with VEE/SIN-gag replicon particles, composed of Venezuelan Equine Encephalitis virus (VEE) replicon RNA and Sindbis surface structure (SIN). i.n./i.m., as compared to any other immunizations, with VEE/SIN-gag resulted in enhanced genital tract, but not serum antibody responses. These data show for the first time that mucosal followed by systemic immunizations with gene delivery systems enhance B cell responses independent of the mucosal homing receptors α4β7 or αEβ7.