1. Induction of HIV-1–Specific Mucosal Immune Responses Following Intramuscular Recombinant Adenovirus Serotype 26 HIV-1 Vaccination of Humans
- Author
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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, and Barouch, Dan H
- Subjects
Clinical Research ,Infectious Diseases ,Immunization ,Clinical Trials and Supportive Activities ,Vaccine Related ,Biotechnology ,HIV/AIDS ,Vaccine Related (AIDS) ,Prevention ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,3.4 Vaccines ,Prevention of disease and conditions ,and promotion of well-being ,Infection ,Inflammatory and immune system ,Good Health and Well Being ,AIDS Vaccines ,Adenoviruses ,Human ,Adult ,CD4-Positive T-Lymphocytes ,Colon ,Cytokines ,Enzyme-Linked Immunosorbent Assay ,Female ,HIV Antibodies ,HIV Infections ,HIV-1 ,Humans ,Immunity ,Mucosal ,Injections ,Intramuscular ,Intestinal Mucosa ,Male ,Middle Aged ,Young Adult ,env Gene Products ,Human Immunodeficiency Virus ,HIV ,vaccine ,adenovirus ,mucosal immunity ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
BackgroundDefining 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.MethodsIn 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.ResultsIntramuscular 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.ConclusionsThese 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 registrationNCT01103687.
- Published
- 2015