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SARS-CoV-2 spike-ferritin-nanoparticle adjuvanted with ALFQ induces long-lived plasma cells and cross-neutralizing antibodies.
Shrivastava, Shikha; Carmen, Joshua M; Lu, Zhongyan; Basu, Shraddha; Sankhala, Rajeshwer S; Chen, Wei-Hung; Nguyen, Phuong; Chang, William C; King, Jocelyn; Corbitt, Courtney; Mayer, Sandra; Bolton, Jessica S; Anderson, Alexander; Swafford, Isabella; Terriquez, Guillermo D; Trinh, Hung V; Kim, Jiae; Jobe, Ousman; Paquin-Proulx, Dominic; Matyas, Gary R; Gromowski, Gregory D; Currier, Jeffrey R; Bergmann-Leitner, Elke; Modjarrad, Kayvon; Michael, Nelson L; Joyce, M Gordon; Malloy, Allison M W; Rao, Mangala.
  • Shrivastava S; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Carmen JM; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Lu Z; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Basu S; Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Sankhala RS; Department of Pediatrics, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Chen WH; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Nguyen P; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Chang WC; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • King J; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Corbitt C; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Mayer S; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Bolton JS; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Anderson A; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Swafford I; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Terriquez GD; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Trinh HV; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Kim J; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Jobe O; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Paquin-Proulx D; Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, USA.
  • Matyas GR; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Gromowski GD; Oak Ridge Institute of Science and Education, Oak Ridge, TN, 37831, USA.
  • Currier JR; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Bergmann-Leitner E; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Modjarrad K; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Michael NL; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Joyce MG; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Malloy AMW; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Rao M; Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
NPJ Vaccines ; 8(1): 43, 2023 Mar 18.
Article in English | MEDLINE | ID: covidwho-2281303
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.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Topics: Vaccines / Variants Language: English Journal: NPJ Vaccines Year: 2023 Document Type: Article Affiliation country: S41541-023-00638-6

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Randomized controlled trials Topics: Vaccines / Variants Language: English Journal: NPJ Vaccines Year: 2023 Document Type: Article Affiliation country: S41541-023-00638-6