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. 2020 Nov 25;38(50):7892-7896.
doi: 10.1016/j.vaccine.2020.10.064. Epub 2020 Oct 23.

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

Mimi Guebre-Xabier  1 , Nita Patel  2 , Jing-Hui Tian  3 , Bin Zhou  4 , Sonia Maciejewski  5 , Kristal Lam  6 , Alyse D Portnoff  7 , Michael J Massare  8 , Matthew B Frieman  9 , Pedro A Piedra  10 , Larry Ellingsworth  11 , Gregory Glenn  12 , Gale Smith  13
Affiliations

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

Mimi Guebre-Xabier et al. Vaccine. .

Abstract

There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M™ adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine (NCT04368988).

Keywords: COVID-19; Matrix-M adjuvant; NVX-CoV2373 nanoparticles; Nonhuman primate; SARS-CoV-2; Spike glycoprotein.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Immunogenicity of NVX-CoV2373 vaccine in cynomolgus macaques. (A) Groups of cynomolgus macaques (n = 4 per arm) were immunized weeks 0 and 3 with 2.5 μg NVX-CoV2373 with 25 μg Matrix-M1 or 5 μg or 25 μg NVX-CoV2373 with 50 μg Matrix-M1. Anti-spike EC50 IgG titers were measured weeks 0, 1, 3, and 5. Lines indicate anti-spike IgG titers for individual macaques in each group. (B) Anti-spike EC50 IgG serum titers week 5 in NVX-CoV2373 immunized NHP compared to anti-S EC50 IgG titers in convalescent human sera. (C) ACE2 inhibition IC50 serum titers week 5 NVX-CoV2373 immunized macaques compared to ACE2 inhibition titers in convalescent human sera, (D) Neutralization CPE100 titers against wild type SARS-CoV-2 virus week 5 NVX-CoV2373 immunized macaques compared to neutralization CPE100 titers in convalescent human sera, (E) Subgenomic RNA (sgRNA) copies in BAL fluid days 2 and 4 post challenge SARS-CoV-2 virus in placebo and NVX-CoV2373 immunized macaques. (F) sgRNA copies in nasal swab samples days 2 and 4 post challenge with SARS-CoV-2 virus in placebo and NVX-CoV2373 immunized macaques. Dashed horizontal line indicates the limit of detection (LOD). ConV: Human convalescent serum. BAL: bronchoalveolar lavage.
Fig. 2
Fig. 2
Representative histopathology of lungs from NVX-CoV2373 vaccinated cynomolgus macaques challenged with SARS-CoV-2 (WA1 strain). (A, B, C) Microscopic findings in placebo treated animals includes eosinophils expanding the mucosa of bronchi (asterisks), perivascular mononuclear infiltrates, and mixed inflammation (macrophages and neutrophils) within alveoli. Three out of four animals exhibited a combination of the majority of findings. (D, E, F) Microscopic findings in the group immunized with 2.5 μg NVX-CoV2373/Matrix-M includes minimal to mild mononuclear perivascular infiltrates, and no changes in the bronchi. Rare foreign material was observed in the one male with mixed inflammation. (G, H, I) Histological findings in the group immunized with 5 μg NVX-CoV2373/Matrix-M includes minimal to mild perivascular mononuclear or mixed cell infiltrates (1/1 males and 2/3 females), mild to moderate mixed cell inflammation (1/3 females), and minimal to mild alveolar macrophages (1/1 males and 3/3 females). The female with mixed inflammation additionally observed acellular bacteria and foreign material. (J, K, L) There were no remarkable pathologic changes observed in the bronchi, vascular, or alveoli of animals vaccinated with 25 μg NVX-CoV2373/Matrix-M.
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