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Research Article: Immunogenicity and protection mediated by dmLT and alum adjuvants for an HIV-1 vaccine

Date Published: 2026-01-21

Abstract:
The development of an effective HIV-1 vaccine is of paramount importance to global health. Here, we compared the influence of two adjuvants, Escherichia coli double-mutant heat-labile toxin (dmLT) and alum, on the protective immunity induced by a cyclically permuted trimeric HIV-1 envelope gp120 protein (CycP-gp120) boost. Two groups of rhesus macaques received two modified vaccinia Ankara (MVA)/SHIV C.1086 primes followed by a CycP-gp120 protein boost adjuvanted with either dmLT (n = 9) or alum (n = 10). A group of unvaccinated macaques (n = 8) served as controls. All animals were intrarectally challenged with heterologous SHIV.CH505.375H.dCT weekly for 7 weeks. Following the challenge, dmLT-adjuvanted animals showed significant protection with a vaccine efficacy of 60.8% per exposure ( p = 0.0246). Alum-adjuvanted animals did not show significant protection ( p = 0.1575). Both adjuvants induced comparable envelope-specific binding antibody in serum and rectal secretions with broad V1V2 scaffold-binding specificity. IL-6 plasma concentration correlated positively with V1V2 scaffold-binding and increased after vaccination with both adjuvants. With respect to CD4 T cells, dmLT induced higher frequencies of proliferating central memory (T CM ) and ICOS + cells in blood compared to alum. However, these proliferating CD4 T CM cells showed a decrease in the proportion of gut-homing receptor ?4?7-expressing cells in the dmLT group compared to the alum group at week 2 post-protein boost. The V1V2 scaffold-specific IgG, proliferating T CM and ICOS + CD4 T-cell frequencies, and plasma IL-6 concentration associated positively with protection. These data demonstrate that the vaccine adjuvants dmLT and alum differentially modulate protective helper T-cell responses induced by the CycP-gp120 protein, highlighting the importance of an appropriate adjuvant for eliciting a protective immune response against HIV-1.

Introduction:
Nearly one quarter of the 40 million people living with HIV-1 do not receive antiretroviral treatment (ART), contributing to over 1 million new infections per year. A prophylactic HIV-1 vaccine would significantly limit these new infections in a cost-effective manner ( 1 ). However, an effective HIV-1 vaccine has remained elusive, largely due to the need for it to produce broadly neutralizing antibodies (bnAbs) and a strong CD8 T-cell response without inducing proliferation of target cells. Neutralizing antibodies…

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