1. Immune Monitoring Reveals Fusion Peptide Priming to Imprint Cross-Clade HIV-Neutralizing Responses with a Characteristic Early B Cell Signature.
- Author
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Cheng C, Duan H, Xu K, Chuang GY, Corrigan AR, Geng H, O'Dell S, Ou L, Chambers M, Changela A, Chen X, Foulds KE, Sarfo EK, Jafari AJ, Hill KR, Kong R, Liu K, Todd JP, Tsybovsky Y, Verardi R, Wang S, Wang Y, Wu W, Zhou T, Arnold FJ, Doria-Rose NA, Koup RA, McDermott AB, Scorpio DG, Worobey M, Shapiro L, Mascola JR, and Kwong PD
- Subjects
- AIDS Vaccines immunology, Animals, HIV Antigens immunology, HIV Infections immunology, Hemocyanins metabolism, Immunization, Macaca mulatta, Male, Polysaccharides metabolism, Protein Multimerization, env Gene Products, Human Immunodeficiency Virus immunology, Antibodies, Neutralizing immunology, B-Lymphocytes immunology, HIV Antibodies immunology, Monitoring, Immunologic, Peptides immunology, Recombinant Fusion Proteins immunology
- Abstract
The HIV fusion peptide (FP) is a promising vaccine target. FP-directed monoclonal antibodies from vaccinated macaques have been identified that neutralize up to ∼60% of HIV strains; these vaccinations, however, have involved ∼1 year with an extended neutralization-eclipse phase without measurable serum neutralization. Here, in 32 macaques, we test seven vaccination regimens, each comprising multiple immunizations of FP-carrier conjugates and HIV envelope (Env) trimers. Comparisons of vaccine regimens reveal FP-carrier conjugates to imprint cross-clade neutralizing responses and a cocktail of FP conjugate and Env trimer to elicit the earliest broad responses. We identify a signature, appearing as early as week 6 and involving the frequency of B cells recognizing both FP and Env trimer, predictive of vaccine-elicited breadth ∼1 year later. Immune monitoring of B cells in response to vaccination can thus enable vaccine insights even in the absence of serum neutralization, here identifying FP imprinting, cocktail approach, and early signature as means to improve FP-directed vaccine responses., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Inc.)
- Published
- 2020
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