Antigenic competition in CD4+ T cell responses in a randomized, multicenter, double-blind clinical HIV vaccine trial
Details
Serval ID
serval:BIB_7B3B2ADF9DB1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antigenic competition in CD4+ T cell responses in a randomized, multicenter, double-blind clinical HIV vaccine trial
Journal
Science translational medicine
ISSN
1946-6242 (Electronic)
ISSN-L
1946-6234
Publication state
Published
Issued date
20/11/2019
Peer-reviewed
Oui
Volume
11
Number
519
Pages
eaaw1673
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Publication Status: ppublish
Abstract
T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 10 <sup>10</sup> particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 10 <sup>9</sup> PU of rAd5 Gag/Pol. CD4 <sup>+</sup> T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8 <sup>+</sup> T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4 <sup>+</sup> T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.
Keywords
AIDS Vaccines/immunology, Adolescent, Adult, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, Double-Blind Method, Epitopes/immunology, Female, HIV Antigens/immunology, Humans, Male, Middle Aged, Vaccination, Young Adult, env Gene Products, Human Immunodeficiency Virus/immunology, gag Gene Products, Human Immunodeficiency Virus/immunology
Pubmed
Web of science
Open Access
Yes
Create date
30/11/2019 12:39
Last modification date
23/04/2024 6:00