Induction of HIV-1–Specific Mucosal Immune Responses Following Intramuscular Recombinant Adenovirus Serotype 26 HIV-1 Vaccination of Humans

• Published in: The Journal of infectious diseases Vol. 211; no. 4; pp. 518 - 528
• Main Authors: Baden, Lindsey R., Liu, Jinyan, Li, Hualin, Johnson, Jennifer A., Walsh, Stephen R., Kleinjan, Jane A., Engelson, Brian A., Peter, Lauren, Abbink, Peter, Milner, Danny A., Golden, Kevin L., Viani, Kyle L., Stachler, Matthew D., Chen, Benjamin J., Pau, Maria G., Weijtens, Mo, Carey, Brittany R., Miller, Caroline A., Swann, Edith M., Wolff, Mark, Loblein, Hayley, Seaman, Michael S., Dolin, Raphael, Barouch, Dan H.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.02.2015
• Subjects: Adenovirus; Adenoviruses, Human - immunology; Adult; AIDS Vaccines - administration & dosage; AIDS Vaccines - adverse effects; AIDS Vaccines - immunology; CD4-Positive T-Lymphocytes - immunology; Colon - immunology; Colon - pathology; Cytokines - blood; env Gene Products, Human Immunodeficiency Virus - immunology; Enzyme-Linked Immunosorbent Assay; Female; HIV Antibodies - blood; HIV Antibodies - immunology; HIV Infections - prevention & control; HIV-1 - immunology; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunity, Mucosal - immunology; Injections, Intramuscular; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Major and Brief Reports; Male; Middle Aged; Young Adult; vaccine; HIV; adenovirus; mucosal immunity
• DOI: 10.1093/infdis/jiu485
• ISSN: 0022-1899

Background. Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans. Methods. In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed. Results. Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4⁺ T lymphocytes following vaccination by either histopathology or flow cytometry. Conclusions. These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.