Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials.
Détails
Télécharger: 34843602_BIB_F1241293379B.pdf (3200.66 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_F1241293379B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials.
Périodique
PLoS pathogens
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
11/2021
Peer-reviewed
Oui
Volume
17
Numéro
11
Pages
e1010016
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies. Trial registration: ClinicalTrials.gov NCT00801697, NCT00961883, NCT02207920, NCT00125970, NCT02852005).
Mots-clé
AIDS Vaccines/administration & dosage, AIDS Vaccines/immunology, Adenoviridae/genetics, Adult, Female, Genetic Vectors/classification, Genetic Vectors/genetics, HIV Antibodies/immunology, HIV Antigens/immunology, HIV Infections/immunology, HIV Infections/prevention & control, HIV Infections/virology, HIV-1/genetics, HIV-1/immunology, Humans, Immunity, Humoral, Immunoglobulin G/immunology, Male, Vaccine Development, Vaccines, DNA/administration & dosage, Vaccines, DNA/immunology, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/12/2021 10:31
Dernière modification de la notice
08/08/2024 6:42