Phosphate-mediated coanchoring of RBD immunogens and molecular adjuvants to alum potentiates humoral immunity against SARS-CoV-2

• Type of Material: Article
• Authors: Guido Silvestri, Emory University; Kristen A Rodrigues, Massachusetts Institute of Technology; Sergio A Rodriguez-Aponte, Massachusetts Institute of Technology; Neil C Dalvie, Massachusetts Institute of Technology; Jeong H Lee, Scripps Research Institute; Wuhbet Abraham, Massachusetts Institute of Technology; Diane G Carnathan, Scripps Research Institute; Luis E Jimenez, Emory University; Julia T Ngo, Emory University; Jason YH Chang, Massachusetts Institute of Technology; Zeli Zhang, Scripps Research Institute; Jingyou Yu, Harvard Medical School; Aiquan Chang, Harvard Medical School; Catherine Nakao, La Jolla Institute for Immunology; Benjamin Goodwin, La Jolla Institute for Immunology; CA Naranjo, Massachusetts Institute of Technology; L Zhang, Massachusetts Institute of Technology; M Silva, Massachusetts Institute of Technology; DH Barouch, Massachusetts Institute of Technology; S Crotty, Scripps Research Institute; JC Love, Massachusetts Institute of Technology; DJ Irvine, Massachusetts Institute of Technology
• Language: English
• Date: 2021-12-01
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/sciadv.abj6538
• Title of Journal or Parent Work: SCIENCE ADVANCES
• Volume: 7
• Issue: 50
• Start Page: eabj6538
• End Page: eabj6538
• Grant/Funding Information: We acknowledge support from the NIH [the Koch Institute Core grants P30-CA14051, P51-OD011132 (YNPRC base grant), UM1AI144462, and NIAID R01 AI145629], the Bill & Melinda Gates Foundation (INV-002740), and the Ragon Institute of MGH, MIT, and Harvard. This material is based on work supported in part by the U.S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT, under Cooperative Agreement Number W911NF-18-2-0048. D.J.I. is an investigator of the Howard Hughes Medical Institute.
• Keywords: ANTIGEN ADSORPTION; BINDING; COVID-19; DNA; Science & Technology; VACCINES; Multidisciplinary Sciences; Science & Technology - Other Topics; ANTIBODY-RESPONSES
• Research Categories: Engineering, Materials Science; Biology, Virology; Engineering, Biomedical; Engineering, Chemical

Abstract

There is a need for additional rapidly scalable, low-cost vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to achieve global vaccination. Aluminum hydroxide (alum) adjuvant is the most widely available vaccine adjuvant but elicits modest humoral responses. We hypothesized that phosphate-mediated coanchoring of the receptor binding domain (RBD) of SARS-CoV-2 together with molecular adjuvants on alum particles could potentiate humoral immunity by promoting extended vaccine kinetics and codelivery of vaccine components to lymph nodes. Modification of RBD immunogens with phosphoserine (pSer) peptides enabled efficient alum binding and slowed antigen clearance, leading to notable increases in germinal center responses and neutralizing antibody titers in mice. Adding phosphate-containing CpG or saponin adjuvants to pSer-RBD:alum immunizations synergistically enhanced vaccine immunogenicity in mice and rhesus macaques, inducing neutralizing responses against SARS-CoV-2 variants. Thus, phosphate-mediated coanchoring of RBD and molecular adjuvants to alum is an effective strategy to enhance the efficacy of SARS-CoV-2 subunit vaccines.