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
Author(s)
Kallas E.G., Grunenberg N.A., Yu C., Manso B., Pantaleo G., Casapia M., Baden L.R., Valencia J., Sobieszczyk M., Van Tieu H., Allen M., Hural J., Graham B.S., Kublin J., Gilbert P.B., Corey L., Goepfert P.A., McElrath M.J., Johnson R.P., Huang Y., Frahm N.
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
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 13:39
Last modification date
23/04/2024 7:00
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