A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine Is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model

Johnston, Sara C.; Ricks, Keersten M.; Lakhal-Naouar, Inès; Jay, A. Nelson; Subra, Caroline; Raymond, Jo Lynne; King, Hannah A. D.; Rossi, Franco; Clements, Tamara L.; Fetterer, David P.; Tostenson, Samantha; Cincotta, Camila Macedo; Hack, Holly R.; Kuklis, Caitlin; Soman, Sandrine; King, Jocelyn; Peachman, Kristina K.; Kim, Do-Hoon; Chen, Wei‐Hung; Sankhala, Rajeshwer S.; Martinez, Elizabeth; Hajduczki, Agnes; Chang, William C.; Choe, Misook; Thomas, Paul; Peterson, Caroline E.; Anderson, Alexander R.A.; Swafford, Isabella; Currier, Jeffrey R.; Paquin‐Proulx, Dominic; Jagodzinski, Linda L.; Matyas, Gary R.; Rao, Mangala; Gromowski, Gregory D.; Peel, Sheila A.; White, Lauren E.; Smith, Jeffrey M.; Hooper, Jay W.; Michael, Nelson L.; Modjarrad, Kayvon; Joyce, Michael; Nalca, Aysegul; Bolton, Diane L.; Pitt, M. Louise M.

doi:10.3390/vaccines10050717

Cited by 18 publications

(8 citation statements)

References 38 publications

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“…A SAPN that is assembled strictly from protein components may provide better overall vaccine stability. The SAPN based on iron-transporting protein, ferritin, has been chosen as vaccine carrier for being constituted strictly by protein subunit [ 11 , 12 ]. It has good thermostability when exposed to high temperatures but long-term storage data for ferritin-based vaccines have not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

A Thermal-Stable Protein Nanoparticle That Stimulates Long Lasting Humoral Immune Response

Wong

Liou

Kan³

2023

Vaccines

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A thermally stable vaccine platform is considered the missing piece of vaccine technology. In this article, we reported the creation of a novel protein nanoparticle and assessed its ability to withstand extended high temperature incubation while stimulating a long-lasting humoral immune response. This protein nanoparticle was assembled from a fusion protein composed of an amphipathic helical peptide derived from the M2 protein of the H5N1 influenza virus (AH3) and a superfolder green fluorescent protein (sfGFP). Its proposed structure was modeled according to transmission electronic microscope (TEM) images of protein nanoparticles. From this proposed protein model, we created a mutant with two gain-of-function mutations that work synergistically on particle stability. A protein nanoparticle assembled from this gain-of-function mutant is able to remove a hydrophobic patch from its surface. This gain-of-function mutant also contributes to the higher thermostability of protein nanoparticles and stimulates a long lasting humoral immune response after a single immunization. This assembled nanoparticle showed increasing particle stability at higher temperatures and salt concentrations. This novel protein nanoparticle may serve as a thermally-stable platform for vaccine development.

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Section: Introductionmentioning

confidence: 99%

A Thermal-Stable Protein Nanoparticle That Stimulates Long Lasting Humoral Immune Response

Wong

Liou

Kan³

2023

Vaccines

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“…The Novavax vaccine, composed of the Spike protein adjuvanted by Matrix-M™ (a saponin-based adjuvant), was tested in this model, presenting neutralizing antibodies; thus, the animals were protected from respiratory infection and pulmonary disease upon intranasal and intratracheal challenge [ 48 ]. The ferritin-Spike nanoparticle proposed by the Army Institutes of Research from the United States also used the Cynomolgus model, revealing robust humoral and cellular immune responses, along with reduced lung lesions after SARS-CoV-2 infection [ 49 ].…”

Section: Resultsmentioning

confidence: 99%

Animal Models to Test SARS-CoV-2 Vaccines: Which Ones Are in Use and Future Expectations

2022

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Since late 2019 and early 2020, with the emergence of the COVID-19 pandemic, scientists are rushing to develop treatment and prevention methods to combat SARS-CoV-2. Among these are vaccines. In view of this, the use of animals as experimental models, both to investigate the immunopathology of the disease and to evaluate the efficacy and safety of vaccines, is mandatory. This work aims to describe, through recent scientific articles found in reliable databases, the animal models used for the in vivo testing of COVID-19 vaccines, demonstrating some possibilities of more advantageous/gold-standard models for SARS-CoV-2 vaccines. The majority of the studies use rodents and primates. Meanwhile, the most adequate model to be used as the gold standard for in vivo tests of COVID-19 vaccines is not yet conclusive. Promising options are being discussed as new tests are being carried out and new SARS-CoV-2 variants are emerging.

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“…We previously reported the development of a self-assembling protein nanoparticle that displays 8 copies of the pre-fusion stabilized SARS-CoV-2 spike glycoprotein trimer, in an ordered array (SpFN) that was adjuvanted with ALFQ 18 . This vaccine formulation showed efficacy against the original SARS-CoV-2 variant (WA1) in K18-hACE2 transgenic mice, Rhesus macaque, and Cynomolgus models and against VOCs Alpha (B.1.1.7) and Beta (B.1.351) in a Syrian golden hamster challenge model 20 , 22 , 33 .…”

Section: Discussionmentioning

confidence: 99%

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

Shrivastava

Carmen

et al. 2023

npj Vaccines

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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.

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A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine Is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model

Cited by 18 publications

References 38 publications

A Thermal-Stable Protein Nanoparticle That Stimulates Long Lasting Humoral Immune Response

A Thermal-Stable Protein Nanoparticle That Stimulates Long Lasting Humoral Immune Response

Animal Models to Test SARS-CoV-2 Vaccines: Which Ones Are in Use and Future Expectations

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

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