Common Features of Mucosal and Peripheral Antibody Responses Elicited by Candidate HIV-1 Vaccines in Rhesus Monkeys

Human mucosal surfaces represent the major portal of entry for human immunodeficiency virus type 1 (HIV-1) and a prophylactic vaccine will likely need to elicit protective antibody responses at mucosal sites. However, mucosal humoral immune responses following vaccination are poorly characterized. In this study we collected sera and colorectal mucosal secretions from adult rhesus monkeys immunized with intramuscular injection of either 2×10¹⁰ vial particles of adenovirus serotype 35 (Ad35) at week 0 and Ad26 at week 24 encoding SIV Env/Gag/Pol (Ad/Ad) or 0.25 mg recombinant HIV-1 Env protein with adjuvant at weeks 0, 4, 8, 12, 16 and 20. ELISA assays were performed to assess of the magnitude, durability and isotype of vaccine-elicited antibody responses. Neutralizing assay was performed to determine the functionality of antibody responses and peptide microarrays were performed to determine the epitope specificities of vaccine-elicited antibodies. We found that both Ad/Ad and protein immunization elicited potent and durable Env-specific IgG and IgA responses in sera and mucosal secretions. Vaccine-elicited mucosal IgG and IgA responses correlated with their counterparts in sera. Both Ad/Ad and protein immunization elicited IgG1 and IgG3 responses in serum and mucosal secretions. Lastly, mucosal secretions and sera from vaccinated monkeys exhibited neutralizing activity and vaccine-elicited Env-specific mucosal and serum IgG shared similar epitope specificities. These data suggest that intramuscular immunization of both Ad-vectored and protein-based candidate HIV-1 vaccines elicit potent and durable antibody responses at colorectal mucosa mirroring those in serum and vaccine-elicited peripheral and mucosal humoral immune responses are likely immunologically coordinated.