Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial.
Details
Serval ID
serval:BIB_82AFFC2A801F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial.
Journal
PLoS pathogens
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
06/2020
Peer-reviewed
Oui
Volume
16
Number
6
Pages
e1008522
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.
Keywords
AIDS Vaccines/administration & dosage, AIDS Vaccines/genetics, AIDS Vaccines/immunology, Adolescent, Adult, CD8-Positive T-Lymphocytes/immunology, Female, Genetic Vectors/administration & dosage, Genetic Vectors/genetics, Genetic Vectors/immunology, HIV Antigens/administration & dosage, HIV Antigens/genetics, HIV Antigens/immunology, Humans, Interferon-gamma/immunology, Male, Middle Aged, Poxviridae/genetics, Poxviridae/immunology, T-Lymphocytes, Helper-Inducer/metabolism, Vaccines, DNA/administration & dosage, Vaccines, DNA/genetics, Vaccines, DNA/immunology, env Gene Products, Human Immunodeficiency Virus/administration & dosage, env Gene Products, Human Immunodeficiency Virus/genetics, env Gene Products, Human Immunodeficiency Virus/immunology
Pubmed
Web of science
Open Access
Yes
Create date
03/07/2020 18:07
Last modification date
08/08/2024 7:36