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- Title
Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.
- Authors
Om, Kier; Paquin-Proulx, Dominic; Montero, Maria; Peachman, Kristina; Shen, Xiaoying; Wieczorek, Lindsay; Beck, Zoltan; Weiner, Joshua A.; Kim, Dohoon; Li, Yifan; Mdluli, Thembi; Shubin, Zhanna; Bryant, Christopher; Sharma, Vishakha; Tokarev, Andrey; Dawson, Peter; White, Yohann; Appelbe, Oliver; Klatt, Nichole R.; Tovanabutra, Sodsai
- Abstract
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. Author summary: A clinically safe liposomal adjuvant can drive antibody effector activity towards increased phagocytic function relative to alum and this activity mediates protection against stringent mucosal SHIV infection in macaques.
- Subjects
ANKARA (Turkey); VACCINIA; VACCINE effectiveness; ANTIBODY formation; VACCINES; MACAQUES; ANTIBODY-dependent cell cytotoxicity; LIPOSOMES
- Publication
PLoS Pathogens, 2020, Vol 16, Issue 9, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1008764