Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.
Adjuvants, Immunologic
/ administration & dosage
Adolescent
Adult
Animals
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Antibody Formation
/ immunology
Double-Blind Method
Female
HIV Antibodies
/ immunology
HIV Infections
/ immunology
HIV-1
/ drug effects
Humans
Macaca mulatta
Male
Middle Aged
SAIDS Vaccines
/ immunology
Simian Acquired Immunodeficiency Syndrome
/ immunology
Simian Immunodeficiency Virus
/ drug effects
Young Adult
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
27
03
2020
accepted:
30
06
2020
revised:
21
09
2020
pubmed:
4
9
2020
medline:
22
10
2020
entrez:
4
9
2020
Statut:
epublish
Résumé
To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants.
Identifiants
pubmed: 32881968
doi: 10.1371/journal.ppat.1008764
pii: PPATHOGENS-D-20-00604
pmc: PMC7505435
doi:
Substances chimiques
Adjuvants, Immunologic
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
HIV Antibodies
0
SAIDS Vaccines
0
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008764Subventions
Organisme : NIAID NIH HHS
ID : P01 AI120756
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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