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Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge

  1. Author:
    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
    Estes, Jacob D.
    Matyas, Gary R.
    Ferrari, Guido
    Alving, Carl R.
    Tomaras, Georgia D.
    Ackerman, Margaret E.
    Michael, Nelson L.
    Robb, Merlin L.
    Polonis, Victoria
    Rolland, Morgane
    Eller, Michael A.
    Rao, Mangala
    Bolton, Diane L.

  2. Author Address

    Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA.Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC USA.Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.EMMES, Rockville, MD USA.Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.Perkin Elmer Spain, Tres Cantos, Spain.Caribe Consulting Ltd, Unit C, Kingston, Jamaica.NanoString Technol, Seattle, WA USA.Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
    1. Year: 2020
    2. Date: SEP
  2. Journal: PLOS PATHOGENS
  3. PUBLIC LIBRARY SCIENCE,
    1. 16
    2. 9
    3. Pages: pii: e1008764
  5. Type of Article: Article
  6. Article Number: ARTN e1008764
  7. ISSN: 1553-7366
  1. Abstract:

    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. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1371/journal.ppat.1008764
  3. View record in Web of Science®
  4. WOS: 000570245600004

Library Notes

  1. Fiscal Year: FY2020-2021
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