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

• DOI: 10.1371/journal.ppat.1008764
• Publication Date: 2020-09-03T17:55:04Z
• Authors: Kier Om; Dominic Paquin-Pr...; Maria Montero; Kristina Peachman; Xiaoying Shen; Lindsay Wieczorek; Zoltan Beck; Joshua A. Weiner; Dohoon Kim; Yifan Li; Thembi Mdluli; Zhanna Shubin; Christopher Bryant; Vishakha Sharma; Andrey Tokarev; Peter Dawson; Yohann White; Oliver Appelbe; Nichole R. Klatt; Sodsai Tovanabutra; Jacob D. Estes; Gary R. Matyas; Guido Ferrari; Carl R. Alving; Georgia D. Tomaras; Margaret E. Ackerman; Nelson L. Michael; Merlin L. Robb; Victoria Polonis; Morgane Rolland; Michael A. Eller; Mangala Rao; Diane L. Bolton
• Keywords: Adult; Male; Adolescent; QH301-705.5; Simian Acquired Immunodeficiency Syndrome; HIV Infections; HIV Antibodies; Antibodies, Viral; Young Adult; 03 medical and health sciences; Adjuvants, Immunologic; Double-Blind Method; Animals; Humans; Biology (General); 0303 health sciences; SAIDS Vaccines; RC581-607; Middle Aged; Antibodies, Neutralizing; Macaca mulatta; 3. Good health; Antibody Formation; HIV-1; Female; Simian Immunodeficiency Virus; Immunologic diseases. Allergy; Research Article

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.