NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge

Guebre‐Xabier, Mimi; Patel, Nita; Tian, Jing-Hui; Zhou, Bin; Maciejewski, Sonia; Lam, Kristal; Portnoff, Alyse D.; Massare, Michael J.; Frieman, Matthew B.; Piedra, Pedro A.; Ellingsworth, Larry; Glenn, Gregory M.; Smith, Gale

doi:10.1101/2020.08.18.256578

Cited by 81 publications

(120 citation statements)

References 13 publications

(6 reference statements)

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“…Novavax has tested their recombinant spike protein based vaccine (Figure 3e) with Matrix-M adjuvant in cynomolgus macaques in three different doses (2.5 ug, 5 ug and 25 ug) in a 3 week prime boost interval via the intramuscular route (Table 1) 82,83 . Animals were then challenged on day 37 with 10 4 TCID of virus in/it.…”

Section: Results From Nhpsmentioning

confidence: 99%

SARS-CoV-2 vaccines in development

Krammer

2020

Nature

1,871

1,781

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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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Section: Results From Nhpsmentioning

confidence: 99%

SARS-CoV-2 vaccines in development

Krammer

2020

Nature

1,871

1,781

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“…Our results also demonstrated that the neutralizing titre elicited by S-2P is higher than S-WT with partial furin cleavage. This S-2P design has been adopted in other cases of the vaccine development including NVX-CoV2373 [52] and mRNA-1273 [53] that are in clinical trials. Whether the high neutralization titre by the recombinant S-2P proteins based on BEVS could translate into spectacular efficacy against COVID-19 and even SARS-CoV-2 infection remains to be determined in animal models, such as hACE2 transgenic mouse [54], hamsters [55], and monkeys [19].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 spike produced in insect cells elicits high neutralization titres in non-human primates

Zheng

et al. 2020

Emerging Microbes & Infections

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The current coronavirus disease 2019 (COVID-19) pandemic was the result of the rapid transmission of a highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is no efficacious vaccine or therapeutic. Toward the development of a vaccine, here we expressed and evaluated as potential candidates four versions of the spike (S) protein using an insect cell expression system: receptor binding domain (RBD), S1 subunit, the wild-type S ectodomain (S-WT), and the prefusion trimer-stabilized form (S-2P). We showed that RBD appears as a monomer in solution, whereas S1, S-WT, and S-2P associate as homotrimers with substantial glycosylation. Cryo-electron microscopy analyses suggested that S-2P assumes an identical trimer conformation as the similarly engineered S protein expressed in 293 mammalian cells but with reduced glycosylation. Overall, the four proteins confer excellent antigenicity with convalescent COVID-19 patient sera in enzyme-linked immunosorbent assay (ELISA), yet show distinct reactivities in immunoblotting. RBD, S-WT and S-2P, but not S1, induce high neutralization titres (>3-log) in mice after a three-round immunization regimen. The high immunogenicity of S-2P could be maintained at the lowest dose (1 μg) with the inclusion of an aluminium adjuvant. Higher doses (20 μg) of S-2P can elicit high neutralization titres in non-human primates that exceed 40-times the mean titres measured in convalescent COVID-19 subjects. Our results suggest that the prefusion trimer-stabilized SARS-CoV-2 S-protein from insect cells may offer a potential candidate strategy for the development of a recombinant COVID-19 vaccine.

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“…To increase immunogenicity, the saponin-based adjuvant Matrix-M is included in the vaccine; spike protein subunit and adjuvant are mixed prior to injection [ 59 ]. NVX-CoV2373 was first tested in macaques ( Macaca fascicularis ) that were immunized with the vaccine and challenged with the native virus intranasally and intratracheally [ 60 ]. The monkeys were protected against COVID-19 and did not exhibit any symptoms of upper or lower airway infection or pulmonary disease.…”

Section: Current Status Of Vaccine Developmentmentioning

confidence: 99%

Current State of the First COVID-19 Vaccines

Prüβ

2021

Vaccines

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SARS CoV-2 and its associated disease COVID-19 has devastated the world during 2020. Masks and social distancing could be efficient if done by large proportions of the population, but pandemic fatigue has decreased their efficacy. Economic shut downs come with large price tags and cannot be a long term solution either. The announcements by three vaccine manufacturers in November that their vaccines are 90% or more effective has given hope to at least those in the population who plan to get vaccinated as soon as a scientifically and medically sound vaccine becomes available. This review summarizes the underlying design strategies and current status of development of the nine vaccines that were in phase III trial on 8 November 2020. Contracts between vaccine manufacturing companies and governments aim at distributing the vaccine to a large part of the world population. Questions remain how the temperature sensitive mRNA vaccines will be transported and/or stored and how vaccination will be prioritized within each country. Additionally, current contracts do not cover all countries, with a serious gap in Africa and South America. The second part of this review will detail current distribution plans and remaining challenges with vaccine accessibility and acceptance.

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NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge

Cited by 81 publications

References 13 publications

SARS-CoV-2 vaccines in development

SARS-CoV-2 vaccines in development

SARS-CoV-2 spike produced in insect cells elicits high neutralization titres in non-human primates

Current State of the First COVID-19 Vaccines

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