Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization
Mallika Sastry, Anita Changela, Jason Gorman, Kai Xu, Gwo‐Yu Chuang, Chen‐Hsiang Shen, Cheng Cheng, Hui Geng, Sijy O’Dell, Li Ou, Reda Rawi, Mateo Reveiz, Guillaume B. E. Stewart-Jones, Shuishu Wang, Baoshan Zhang, Tongqing Zhou, Andrea Biju, Michael Chambers, Xuejun Chen, Angela R. Corrigan, Bob C. Lin, Mark K. Louder, Krisha McKee, Alexandra F. Nazzari, Adam S. Olia, Danealle K. Parchment, Edward K. Sarfo, Tyler Stephens, Jonathan Stuckey, Yaroslav Tsybovsky, Raffaello Verardi, Yiran Wang, Cheng-Yan Zheng, Yuling Chen, Nicole A. Doria‐Rose, Adrian B. McDermott, John R. Mascola, Peter D. Kwong
Abstract
The HIV-1 fusion peptide has been identified as a site for elicitation of broadly neutralizing antibodies, with prior studies demonstrating that priming with fusion peptide-based immunogens and boosting with soluble envelope (Env) trimers can elicit cross-clade HIV-1-neutralizing responses. To improve the neutralizing breadth and potency of fusion peptide-directed responses, we evaluated vaccine regimens that incorporated diverse fusion peptide-conjugates and Env trimers with variation in fusion peptide length and sequence. We found that variation in peptide length during prime elicits enhanced neutralizing responses in mice and guinea pigs. We identified vaccine-elicited murine monoclonal antibodies from distinct classes capable of cross-clade neutralization and of diverse fusion peptide recognition. Our findings lend insight into improved immunogens and regimens for HIV-1 vaccine development.