1. Fusion peptide priming reduces immune responses to HIV-1 envelope trimer base.
- Author
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Corrigan AR, Duan H, Cheng C, Gonelli CA, Ou L, Xu K, DeMouth ME, Geng H, Narpala S, O'Connell S, Zhang B, Zhou T, Basappa M, Boyington JC, Chen SJ, O'Dell S, Pegu A, Stephens T, Tsybovsky Y, van Schooten J, Todd JP, Wang S, Doria-Rose NA, Foulds KE, Koup RA, McDermott AB, van Gils MJ, Kwong PD, and Mascola JR
- Subjects
- Animals, Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Female, Humans, Immunization, Immunoglobulin Fab Fragments immunology, Macaca mulatta, Male, Models, Biological, Antibody Formation immunology, HIV-1 immunology, Peptides immunology, Protein Multimerization, Recombinant Fusion Proteins metabolism, env Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
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., Competing Interests: Declaration of interests P.D.K., J.R.M., L.O., Y.T., K.X., and B.Z. are inventors on U.S. Patent Application 62/735,188 filed March 26, 2020, entitled “HIV-1 ENV fusion peptide immunogens and their use.” The other authors declare no competing interests., (Published by Elsevier Inc.)
- Published
- 2021
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