NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge
Mimi Guebre-Xabier, Nita Patel, Jing-Hui Tian, Bin Zhou, Sonia Maciejewski, Kristal Lam, Alyse D Portnoff, Michael J Massare, Matthew B Frieman, Pedro A Piedra, Larry Ellingsworth, Gregory Glenn, Gale Smith, Mimi Guebre-Xabier, Nita Patel, Jing-Hui Tian, Bin Zhou, Sonia Maciejewski, Kristal Lam, Alyse D Portnoff, Michael J Massare, Matthew B Frieman, Pedro A Piedra, Larry Ellingsworth, Gregory Glenn, Gale Smith
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.
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.
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Figures
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.
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.
References
- Jing-Hui Tian, Nita Patel, Robert Haupt, Haixia Zhou, Stuart Weston, Holly Hammond, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. bioRxiv 2020; doi: .
- Keech C., Albert G., Cho I., Robertson A., Reed P., Neal S., Plested J.S., Zhu M., Cloney-Clark S., Zhou H., Smith G., Patel N., Frieman M.B., Haupt R.E., Logue J., McGrath M., Weston S., Piedra P.A., Desai C., Callahan K., Lewis M., Price-Abbott P., Formica N., Shinde V., Fries L., Lickliter J.D., Griffin P., Wilkinson B., Glenn G.M. Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020 doi: 10.1056/NEJMoa2026920.
- Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.-L., Abiona O., Graham B.S., McLellan J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. doi: 10.1126/science:abb2507.
- Wölfel R., Corman V.M., Guggemos W., Seilmaier M., Zange S., Müller M.A., Niemeyer D., Jones T.C., Vollmar P., Rothe C., Hoelscher M., Bleicker T., Brünink S., Schneider J., Ehmann R., Zwirglmaier K., Drosten C., Wendtner C. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465–469. doi: 10.1038/s41586-020-2196-x.
- Shan C., Yao Y.-F., Yang X.-L., Zhou Y.-W., Gao G.e., Peng Y., Yang L., Hu X., Xiong J., Jiang R.-D., Zhang H.-J., Gao X.-X., Peng C., Min J., Chen Y., Si H.-R., Wu J., Zhou P., Wang Y.-Y., Wei H.-P., Pang W., Hu Z.-F., Lv L.-B., Zheng Y.-T., Shi Z.-L., Yuan Z.-M. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques. Cell Res. 2020;30(8):670–677. doi: 10.1038/s41422-020-0364-z.
- Chandrashekar A., Liu J., Martinot A.J., McMahan K., Mercado N.B., Peter L., Tostanoski L.H., Yu J., Maliga Z., Nekorchuk M., Busman-Sahay K., Terry M., Wrijil L.M., Ducat S., Martinez D.R., Atyeo C., Fischinger S., Burke J.S., Slein M.D., Pessaint L., Van Ry A., Greenhouse J., Taylor T., Blade K., Cook A., Finneyfrock B., Brown R., Teow E., Velasco J., Zahn R., Wegmann F., Abbink P., Bondzie E.A., Dagotto G., Gebre M.S., He X., Jacob-Dolan C., Kordana N., Li Z., Lifton M.A., Mahrokhian S.H., Maxfield L.F., Nityanandam R., Nkolola J.P., Schmidt A.G., Miller A.D., Baric R.S., Alter G., Sorger P.K., Estes J.D., Andersen H., Lewis M.G., Barouch D.H. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science. 2020;369(6505):812–817. doi: 10.1126/science:abc4776.
- Gao Q., Bao L., Mao H., Wang L., Xu K., Yang M., Li Y., Zhu L., Wang N., Lv Z., Gao H., Ge X., Kan B., Hu Y., Liu J., Cai F., Jiang D., Yin Y., Qin C., Li J., Gong X., Lou X., Shi W., Wu D., Zhang H., Zhu L., Deng W., Li Y., Lu J., Li C., Wang X., Yin W., Zhang Y., Qin C. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020;369(6499):77–81. doi: 10.1126/science:abc1932.
- Neeltje van Doremalen, Teresa Lambe, Alexandra Spencer, Sandra Belij-Rammerstorfer, Jyothi N. Purushotham, Julia R. Port, et al. ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques. bioRXiv. 2020; https://doi:10.1101/2020.05.13.093195.
- Yu J., Tostanoski L.H., Peter L., Mercado N.B., McMahan K., Mahrokhian S.H., Nkolola J.P., Liu J., Li Z., Chandrashekar A., Martinez D.R., Loos C., Atyeo C., Fischinger S., Burke J.S., Slein M.D., Chen Y., Zuiani A., Lelis F.J.N., Travers M., Habibi S., Pessaint L., Van Ry A., Blade K., Brown R., Cook A., Finneyfrock B., Dodson A., Teow E., Velasco J., Zahn R., Wegmann F., Bondzie E.A., Dagotto G., Gebre M.S., He X., Jacob-Dolan C., Kirilova M., Kordana N., Lin Z., Maxfield L.F., Nampanya F., Nityanandam R., Ventura J.D., Wan H., Cai Y., Chen B., Schmidt A.G., Wesemann D.R., Baric R.S., Alter G., Andersen H., Lewis M.G., Barouch D.H. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020;369(6505):806–811. doi: 10.1126/science:abc6284.
- Corbett K.S., Flynn B., Foulds K.E., Francica J.R., Boyoglu-Barnum S., Werner A.P., Flach B., O’Connell S., Bock K.W., Minai M., Nagata B.M., Andersen H., Martinez D.R., Noe A.T., Douek N., Donaldson M.M., Nji N.N., Alvarado G.S., Edwards D.K., Flebbe D.R., Lamb E., Doria-Rose N.A., Lin B.C., Louder M.K., O’Dell S., Schmidt S.D., Phung E., Chang L.A., Yap C., Todd J.-P., Pessaint L., Van Ry A., Browne S., Greenhouse J., Putman-Taylor T., Strasbaugh A., Campbell T.-A., Cook A., Dodson A., Steingrebe K., Shi W., Zhang Y.i., Abiona O.M., Wang L., Pegu A., Yang E.S., Leung K., Zhou T., Teng I.-T., Widge A., Gordon I., Novik L., Gillespie R.A., Loomis R.J., Moliva J.I., Stewart-Jones G., Himansu S., Kong W.-P., Nason M.C., Morabito K.M., Ruckwardt T.J., Ledgerwood J.E., Gaudinski M.R., Kwong P.D., Mascola J.R., Carfi A., Lewis M.G., Baric R.S., McDermott A., Moore I.N., Sullivan N.J., Roederer M., Seder R.A., Graham B.S. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N Engl J Med. 2020;383(16):1544–1555. doi: 10.1056/NEJMoa2024671.
- Rockx B., Kuiken T., Herfst S., Bestebroer T., Lamers M.M., Oude Munnink B.B., de Meulder D., van Amerongen G., van den Brand J., Okba N.M.A., Schipper D., van Run P., Leijten L., Sikkema R., Verschoor E., Verstrepen B., Bogers W., Langermans J., Drosten C., Fentener van Vlissingen M., Fouchier R., de Swart R., Koopmans M., Haagmans B.L. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020;368(6494):1012–1015. doi: 10.1126/science:abb7314.
- Yang J., Wang W., Chen Z., Lu S., Yang F., Bi Z., Bao L., Mo F., Li X., Huang Y., Hong W., Yang Y., Zhao Y., Ye F., Lin S., Deng W., Chen H., Lei H., Zhang Z., Luo M., Gao H., Zheng Y., Gong Y., Jiang X., Xu Y., Lv Q.I., Li D., Wang M., Li F., Wang S., Wang G., Yu P., Qu Y., Yang L.I., Deng H., Tong A., Li J., Wang Z., Yang J., Shen G., Zhao Z., Li Y., Luo J., Liu H., Yu W., Yang M., Xu J., Wang J., Li H., Wang H., Kuang D., Lin P., Hu Z., Guo W., Cheng W., He Y., Song X., Chen C., Xue Z., Yao S., Chen L.u., Ma X., Chen S., Gou M., Huang W., Wang Y., Fan C., Tian Z., Shi M., Wang F.-S., Dai L., Wu M., Li G., Wang G., Peng Y., Qian Z., Huang C., Lau J.-N., Yang Z., Wei Y., Cen X., Peng X., Qin C., Zhang K., Lu G., Wei X. A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity. Nature. 2020;586(7830):572–577. doi: 10.1038/s41586-020-2599-8.
Source: PubMed