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.
Bibliographical noteFunding Information:
This work was supported by a cooperative agreement (W81XWH-18-2-0040) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the DoD as well as by NIAID, NIH grant P01 AI120756 (X.S., G.D.T.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. General: We thank Khalil Itani, C. Todd Demarco, Thomas Denny for viremia measurements and Celia LaBranche, David Montefiori (Duke University) for SHIV neutralization experiments; Shelly Krebs, Vincent Dussupt for antigen production; Robert Kruse, Susan Brown, Cheryl Thomas for the MVA vaccines; Hannah King for T cell ICS data analysis; Courtney Carrington, Ashley Williams for specimen processing; Meera Bose, Daniel Silas for sequencing (all USMHRP); Katharine Bar (University of Pennsylvania) for viral sequence data interpretation; Mark Lewis and Brad Finneyfrock (Bioqual, Inc.) for execution of the animal study; and Nancy Miller (NIAID, NIH) for the SHIV-1157ipd3N4 viral stock. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense (DoD).
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PubMed: MeSH publication types
- 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.