SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies

Shikha Shrivastava, Joshua M. Carmen, Zhongyan Lu, Shraddha Basu, Rajeshwer S. Sankhala, Wei Hung Chen, Phuong Nguyen, William C. Chang, Jocelyn King, Courtney Corbitt, Sandra Mayer, Jessica S. Bolton, Alexander Anderson, Isabella Swafford, Guillermo D. Terriquez, Hung V. Trinh, Jiae Kim, Ousman Jobe, Dominic Paquin-Proulx, Gary R. MatyasGregory D. Gromowski, Jeffrey R. Currier, Elke Bergmann-Leitner, Kayvon Modjarrad, Nelson L. Michael, M. Gordon Joyce, Allison M.W. Malloy, Mangala Rao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

This study demonstrates the impact of adjuvant on the development of T follicular helper (Tfh) and B cells, and their influence on antibody responses in mice vaccinated with SARS-CoV-2-spike-ferritin-nanoparticle (SpFN) adjuvanted with either Army Liposome Formulation containing QS-21 (SpFN + ALFQ) or Alhydrogel® (SpFN + AH). SpFN + ALFQ increased the size and frequency of germinal center (GC) B cells in the vaccine-draining lymph nodes and increased the frequency of antigen-specific naive B cells. A single vaccination with SpFN + ALFQ resulted in a higher frequency of IL-21-producing-spike-specific Tfh and GC B cells in the draining lymph nodes and spleen, S-2P protein-specific IgM and IgG antibodies, and elicitation of robust cross-neutralizing antibodies against SARS-CoV-2 variants as early as day 7, which was enhanced by a second vaccination. This was associated with the generation of high titer, high avidity binding antibodies. The third vaccination with SpFN + ALFQ elicited high levels of neutralizing antibodies against the Omicron variant. No cross-neutralizing antibodies against Omicron were induced with SpFN + AH. These findings highlight the importance of ALFQ in orchestrating early induction of antigen-specific Tfh and GC B cell responses and long-lived plasma cells in the bone marrow. The early engagement of S-2P specific naive B cells and high titer IgM antibodies shape the development of long-term neutralization breadth.

Original languageEnglish
Article number43
Journalnpj Vaccines
Volume8
Issue number1
DOIs
StatePublished - Dec 2023
Externally publishedYes

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