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

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

Distinct Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals

“…Limitations to functional characterization reported here include use of surrogate endpoints of anti-viral activities, such as the substitution of FcgR3a activation and complement C3b deposition as alternatives to assessing infected cell death or viral lysis, and the use of pseudovirus in neutralization tests and recombinant S proteins in effector function assays. However, assays simplified in these ways have served as correlates of vaccine efficacy in multiple human and animal model studies (81)(82)(83)(84)(85)(86) and represent approaches readily available for deployment in the global effort to understand responses to SARS-CoV-2 infection and define protective immunity.…”

SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity

“…The response to SARS-CoV-2 was facilitated by multiple efforts over the last decade to enable CoV pandemic preparedness, initially based on MERS-CoV vaccine design and development (Wang et al, 2015), phase I vaccine trials (Modjarrad et al, 2019), and a global effort by the Coalition for Epidemic Preparedness Innovations (CEPI) to advance vaccine candidates (Plotkin, 2017). The elucidation of CoV Spike (S) glycoprotein structures (Kirchdoerfer et al, 2016;Walls et al, 2016) allowed structure-based vaccine design of stabilized S glycoprotein immunogens from multiple CoVs (Pallesen et al, 2017), providing a blueprint for SARS-CoV-2 vaccine design .…”

“…Engineered nanoparticle vaccines and their capacity to generate enhanced immune responses in humans are currently being studied and include influenza (NCT03186781; NCT03814720; NCT04579250), Epstein-Barr virus (NCT04645147), malaria (NCT04296279) and a recently described SARS-CoV-2 nanoparticle vaccine (IVX-411) (Walls et al, 2020). Use of potent adjuvants such as liposomal-saponin adjuvants can further enhance the protective immune response (Cawlfield et al, 2019;Lal et al, 2015;Om et al, 2020) even in the context of nanoparticle vaccines (Langowski et al, 2020) (Kaba et al, 2018. Based on the results described herein and data from associated non-human primate experiments (Joyce et al, 2021;King et al, 2021), a S-Ferritin immunogen with a liposomal adjuvant, ALFQ is currently being assessed in a phase I clinical trial (NCT04784767).…”

Adjuvant‐mediated enhancement of the immune response to HIV vaccines

“…MF59 adjuvant, which was used in HVTN702 clinical trial, elicited binding and nnAbs in NHPs [115]. Immunization with liposome-based adjuvant (MPLA formulation adsorbed to alum, ALFA) administrated with subtype C gp145 Env enhanced the ADCP responses against mucosal SHIV challenge, which strongly mediated the protection in macaques [116].…”