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 Matyas; Gregory D Gromowski; Jeffrey R Currier; Elke Bergmann-Leitner; Kayvon Modjarrad; Nelson L Michael; M Gordon Joyce; Allison M W Malloy; Mangala Rao

doi:10.1038/s41541-023-00638-6

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

NPJ Vaccines. 2023 Mar 18;8(1):43. doi: 10.1038/s41541-023-00638-6.

Authors

Shikha Shrivastava^{1

2}, Joshua M Carmen^{1

3}, Zhongyan Lu⁴, Shraddha Basu^{1

2}, Rajeshwer S Sankhala^{2

5}, Wei-Hung Chen^{2

5}, Phuong Nguyen^{1

2}, William C Chang^{2

5}, Jocelyn King⁶, Courtney Corbitt⁶, Sandra Mayer⁶, Jessica S Bolton⁷, Alexander Anderson^{1

8}, Isabella Swafford², Guillermo D Terriquez¹, Hung V Trinh^{1

2}, Jiae Kim^{1

2}, Ousman Jobe^{1

2}, Dominic Paquin-Proulx², Gary R Matyas^{1

3}, Gregory D Gromowski^{3

6}, Jeffrey R Currier^{3

6}, Elke Bergmann-Leitner^{3

7}, Kayvon Modjarrad^{3

5}, Nelson L Michael³, M Gordon Joyce^{2

5}, Allison M W Malloy⁴, Mangala Rao^{9

10}

Affiliations

¹ Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
² Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
³ Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁴ Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁵ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁶ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁷ Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, USA.
⁸ Oak Ridge Institute of Science and Education, Oak Ridge, TN, 37831, USA.
⁹ Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA. mrao@hivresearch.org.
¹⁰ Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA. mrao@hivresearch.org.

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.