Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine

Li, Dapeng; Martinez, David R.; Schäfer, Alexandra; Chen, Haiyan; Barr, Maggie; Sutherland, Laura L.; Lee, Esther; Parks, Rob; Mielke, Dieter; Edwards, W. Daniel; Newman, Amanda; Bock, Kevin W.; Minai, Mahnaz; Nagata, Bianca M.; Gagné, Matthew; Douek, Daniel C.; DeMarco, C. Todd; Denny, Thomas N.; Oguin, Thomas; Brown, April; Rountree, Wes; Wang, Yunfei; Mansouri, Katayoun; Edwards, Robert J.; Ferrari, Guido; Sempowski, Gregory D.; Eaton, Amanda; Tang, Juanjie; Cain, Derek W.; Santra, Sampa; Pardi, Norbert; Weissman, Drew; Tomai, Mark A.; Fox, Christopher B.; Moore, Ian N.; Andersen, Hanné; Lewis, Mark G.; Golding, Hana; Seder, Robert A.; Khurana, Surender; Baric, Ralph S.; Montefiori, David C.; Saunders, Kevin O.; Haynes, Barton F.

doi:10.2139/ssrn.4038516

Cited by 4 publications

(5 citation statements)

References 49 publications

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“…Homotypic SARS-2 RBD or S trimer nanoparticles elicit potent neutralizing antibody responses that exhibit some degree of cross-reactivity across SARS-2 variants and sarbecoviruses ( 34, 35, 65-74 ). Here, we reproduce and extend those results in challenge studies demonstrating protection against SARS-2, including a mismatched variant, using a mosaic-8 RBD nanoparticle vaccine candidate.…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that, although homotypic SARS-2 RBD-mi3 nanoparticles did not confer complete protection against SARS-1, viral loads in lung tissue obtained from immunized animals were greatly reduced compared to control animals: only one of four animals had detectable viral loads in the lungs compared to four of four in the control group, demonstrating that some level of protection was achieved. Interestingly, a similar outcome was reported upon vaccination of aged mice with RBD-scNP, a homotypic SARS-2 RBD-conjugated ferritin nanoparticle that induced neutralizing antibodies against SARS-2 and pre-emergent sarbecoviruses: upon subsequent challenge with mouse-adapted SARS-1, viral loads were significantly reduced, but not absent, in lung tissue (four of five vaccinated animals exhibited reduced, but detectable SARS-1 virus, as compared with five of five with higher viral loads in the control group) ( 74 ).…”

Section: Discussionmentioning

confidence: 99%

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Mosaic RBD nanoparticles protect against multiple sarbecovirus challenges in animal models

Cohen

Doremalen

Greaney

et al. 2022

Preprint

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To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against conserved/relatively-occluded, rather than variable/immunodominant/exposed, epitopes. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicron and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mosaic RBD nanoparticles protect against multiple sarbecovirus challenges in animal models

Cohen

Doremalen

Greaney

et al. 2022

Preprint

Self Cite

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“…and Ab durability, however, these candidates are at earlier clinical development stages 50,51,52 . Future studies on long-lived plasma cells and memory B cell compartment would be warranted to better understand the durability of the Ab responses with mRNA and protein-based vaccines.…”

Section: Discussionmentioning

confidence: 99%

A Beta-containing bivalent SARS-CoV-2 spike protein vaccine candidate with AS03 elicits durable and broad neutralization of variants including Omicron in macaques and confers protection in hamsters

Berry

Pavot

Anosova

et al. 2022

Preprint

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Background Since the beginning of the COVID-19 pandemic, several variants of concern (VOC) have emerged for which there is evidence of an increase in transmissibility, more severe disease, and/or reduced vaccine effectiveness. Effective COVID-19 vaccine strategies are required to achieve broad protective immunity against current and future VOC.Methods We conducted immunogenicity and challenge studies in macaques and hamsters using a bivalent recombinant vaccine formulation containing the SARS-CoV-2 prefusion-stabilized Spike trimers of the parental D614 and the Beta (B.1.351) strains with AS03 adjuvant (CoV2 preS dTM-AS03) in a primary immunization setting. Results We show that a primary immunization with the bivalent CoV2 preS dTM-AS03 elicits broader and durable neutralizing antibody responses against VOC including Omicron BA.1, and SARS-CoV-1 as compared to the parental D614 or Beta variant monovalent vaccines in naïve non-human primates. In addition, the bivalent formulation confers protection against viral challenge with SARS-CoV-2 parental D614G strain as well as Alpha and Beta variant strains in hamsters. Conclusions Our findings demonstrate the potential of a Beta-containing bivalent CoV2 preS dTM-AS03 formulation to provide broad and stable immunogenicity, as well as protection against VOC in naïve populations.

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“…In a similar approach, a homotypic SARS‐CoV‐2 RBD‐based sortase A‐conjugated ferritin nanoparticle, 130 named RBD‐scNP, could induce neutralizing antibodies against SARS‐CoV‐2 and three pre‐emergent sarbecoviruses, SARS‐CoV, WIV1, and RsSHC014. 131 RBD‐scNP protected immunized NHPs from SARS‐CoV‐2 WA‐1, Beta, and Delta variant challenges and protected aged mice from challenges of SARS‐CoV‐2 Beta variant, SARS‐CoV and RsSHC014. In general, the three nanoparticles resulted in high neutralizing antibody levels against not only SARS‐CoV‐2 variants, but also different sarbecoviruses.…”

Section: Broad‐spectrum Anti‐coronavirus Vaccinesmentioning

confidence: 99%

“…Researchers observed that mosaic‐8b elicited strong immune responses and protected K18‐hACE2 mice from SARS‐CoV‐2 and SARS‐CoV challenges. In a similar approach, a homotypic SARS‐CoV‐2 RBD‐based sortase A‐conjugated ferritin nanoparticle, 130 named RBD‐scNP, could induce neutralizing antibodies against SARS‐CoV‐2 and three pre‐emergent sarbecoviruses, SARS‐CoV, WIV1, and RsSHC014 131 . RBD‐scNP protected immunized NHPs from SARS‐CoV‐2 WA‐1, Beta, and Delta variant challenges and protected aged mice from challenges of SARS‐CoV‐2 Beta variant, SARS‐CoV and RsSHC014.…”

Section: Broad‐spectrum Anti‐coronavirus Vaccinesmentioning

confidence: 99%

Development of variant‐proof severe acute respiratory syndrome coronavirus 2, pan‐sarbecovirus, and pan‐β‐coronavirus vaccines

Zhou

Liu

Zhang

et al. 2022

Journal of Medical Virology

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The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants with high transmission rates and striking immune evasion have posed a serious challenge to the application of current first‐generation SARS‐CoV‐2 vaccines. Other sarbecoviruses, such as SARS‐CoV and SARS‐related coronaviruses (SARSr‐CoVs), have the potential to cause outbreaks in the future. These facts call for the development of variant‐proof SARS‐CoV‐2, pan‐sarbecovirus or pan‐β‐CoV vaccines. Several novel vaccine platforms have been used to develop vaccines with broad‐spectrum neutralizing antibody responses and protective immunity to combat the current SARS‐CoV‐2 and its variants, other sarbecoviruses, as well as other β‐CoVs, in the future. In this review, we discussed the major target antigens and protective efficacy of current SARS‐CoV‐2 vaccines and summarized recent advances in broad‐spectrum vaccines against sarbecoviruses and β‐CoVs.

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Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine

Cited by 4 publications

References 49 publications

Mosaic RBD nanoparticles protect against multiple sarbecovirus challenges in animal models

Mosaic RBD nanoparticles protect against multiple sarbecovirus challenges in animal models

A Beta-containing bivalent SARS-CoV-2 spike protein vaccine candidate with AS03 elicits durable and broad neutralization of variants including Omicron in macaques and confers protection in hamsters

Development of variant‐proof severe acute respiratory syndrome coronavirus 2, pan‐sarbecovirus, and pan‐β‐coronavirus vaccines

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