Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans.

Publication Type
Journal Article
Year of Publication
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
J Infect Dis
Date Published
2015 Feb 15
Adenoviruses, Human; Adult; AIDS Vaccines; CD4-Positive T-Lymphocytes; Colon; Cytokines; env Gene Products, Human Immunodeficiency Virus; Enzyme-Linked Immunosorbent Assay; Female; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunity, Mucosal; Injections, Intramuscular; Intestinal Mucosa; Male; Middle Aged; Young Adult

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.