HIV-1-specific B cell immune responses in Rhesus Macaques induced by early region deleted-Ad5 vectors

Abstract

Abstract As a vaccine delivery vector, Adenovirus (Ad) is recognized for its ability to prime immune responses against HIV and other infectious agents. We reported that early region 1B55k (E1B55k) deleted vector induced cellular immunity, transgene-specific antibodies and innate immune signals including chemokines, cytokines and NKG2D ligands MIC A/B in immunized mice. However, the immune priming ability of E3-E1B55k-E4orf1 and E3-E1B55k- E4orf1-4deleted Ad vectors is unknown. Here we compared HIV-specific immune responses generated by E3deleted, E3-E1B55k, E3-E1B55k-E4orf1and E3-E1B55k-E4orf1-4deleted Ad5 vectors encoding full-length single-chain HIVBalgp120 linked to the D1 and D2 domains of rhesus macaque (RM) CD4 (rhFLSC). RMs were immunized twice mucosally with each vector. Blood and rectal tissue were collected at pre and 2-week post-immunization time points. The frequency of plasmablasts (PB)/plasma cells (PC), memory B cells, and antibody secreting cells and antibody titers were assessed by flow cytometry, ELISpot and ELISA, respectively. All vectors induced increased frequencies of rectal PB, PC and rhFLSC specific memory B cells. rhFLSC specific IgA and IgG secreting cells were detected in all immunized macaques; the IgA secreting cells were significantly increased compared to pre values. This was accompanied by elevated levels of IgG, IgG1 and IgA serum antibodies. In summary all four vectors induced B cells responses while retaining replicability. Moreover, the largest deletion, E3-E1B55k-E4orf1-4, improved the transgene carrying capacity of the Ad vector while maintaining the ability to induce B cell immunity important for protective efficacy.