ALFQ Adjuvanted HIV-1 Envelope Protein Vaccination Elicits Durable Functional Antibody and Cellular Responses in Nonhuman Primates

ABSTRACT: Adjuvants play an important role in modulating antigen-specific immune responses. We conducted a comparative adjuvant immunogenicity study in Rhesus macaques using HIV-1 subtype B gp120 envelope protein, B.63521 formulated with aluminum hydroxide gel (AH), or a family of liposomal adjuvants known as Army Liposome Formulation (ALF) to determine their effect on immune responses. ALF comprises saturated phospholipids, cholesterol, and an immunostimulant, monophosphoryl lipid A. Inclusion of a second immunostimulant, a saponin QS-21, or adsorption of the antigen to AH, followed by the addition of ALF generates ALFQ and ALFA, respectively, while the presence of both immunostimulants generates ALFQA. Priming with canarypox vector ALVAC, followed by boosting with ALVAC and gp120 formulated with AH, ALFA, ALFQ or ALFQA resulted in the QS-21-containing liposomal vaccine formulations (ALFQ and ALFQA) outperforming AH-based vaccine formulations (AH, ALFA) by inducing (i) binding antibodies of higher magnitude, durability, and avidity; (ii) higher neutralizing and Fc effector functional antibodies; (iii) higher frequency of durable antigen-specific plasma cells in the bone marrow; (iv) robust Env-specific polyfunctional CD4+ and CD8+ T cell responses and IL-21 producing T follicular helper cells. Transcriptomic analyses revealed that ALFQ and ALFQA vaccine formulations upregulated antiviral and innate immune pathways, including interferon signaling genes. These findings highlight that ALFQ is a highly potent adjuvant that facilitates multifaceted strong durable immune responses in nonhuman primates. Based on these data, an HIV vaccine containing B.63521 and CRF01_AE proteins formulated in ALFQ is currently being evaluated for safety and immunogenicity in a phase 1 clinical trial (NCT05423418).

ORGANISM(S): Macaca mulatta

PROVIDER: GSE308512 | GEO | 2025/12/17

REPOSITORIES: GEO