Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans
Lindsey R Baden, Jinyan Liu, Hualin Li, Jennifer A Johnson, Stephen R Walsh, Jane A Kleinjan, Brian A Engelson, Lauren Peter, Peter Abbink, Danny A Milner Jr, Kevin L Golden, Kyle L Viani, Matthew D Stachler, Benjamin J Chen, Maria G Pau, Mo Weijtens, Brittany R Carey, Caroline A Miller, Edith M Swann, Mark Wolff, Hayley Loblein, Michael S Seaman, Raphael Dolin, Dan H Barouch, Lindsey R Baden, Jinyan Liu, Hualin Li, Jennifer A Johnson, Stephen R Walsh, Jane A Kleinjan, Brian A Engelson, Lauren Peter, Peter Abbink, Danny A Milner Jr, Kevin L Golden, Kyle L Viani, Matthew D Stachler, Benjamin J Chen, Maria G Pau, Mo Weijtens, Brittany R Carey, Caroline A Miller, Edith M Swann, Mark Wolff, Hayley Loblein, Michael S Seaman, Raphael Dolin, Dan H Barouch
Abstract
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.
Clinical trials registration: NCT01103687.
Keywords: HIV; adenovirus; mucosal immunity; vaccine.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Source: PubMed