Fusion peptide priming reduces immune responses to HIV-1 envelope trimer base.

Soluble "SOSIP"-stabilized envelope (Env) trimers are promising HIV-vaccine immunogens. However, they induce high-titer responses against the glycan-free trimer base, which is occluded on native virions. To delineate the effect on base responses of priming with immunogens targeting the fusion peptide (FP) site of vulnerability, here, we quantify the prevalence of trimer-base antibody responses in 49 non-human primates immunized with various SOSIP-stabilized Env trimers and FP-carrier conjugates. Trimer-base responses account for ∼90% of the overall trimer response in animals immunized with trimer only, ∼70% in animals immunized with a cocktail of SOSIP trimer and FP conjugate, and ∼30% in animals primed with FP conjugates before trimer immunization. Notably, neutralization breadth in FP-conjugate-primed animals correlates inversely with trimer-base responses. Our data provide methods to quantify the prevalence of trimer-base responses and reveal that FP-conjugate priming, either alone or as part of a cocktail, can reduce the trimer-base response and improve the neutralization outcome. [Display omitted] • Devise methods to quantify antibody responses targeting the base of HIV-1 Env trimers • Fusion-peptide (FP) priming reduces anti-base responses upon HIV Env trimer boost • Lower percentage of anti-base responses correlates with improved neutralization breadth The exposed base region of soluble HIV-1 Env trimers elicits strong non-neutralizing antibody responses. Corrigan et al. quantify plasma anti-base responses in immunized NHPs and observe a reduction in anti-base responses with fusion-peptide priming. The percentage of anti-base responses correlates inversely with neutralization breadth, providing insights for improving vaccination strategies. [ABSTRACT FROM AUTHOR]