Protection of K18-hACE2 Mice and Ferrets Against SARS-CoV-2 Challenge by a Single-dose Mucosal Immunization with a Parainfluenza Virus 5-based COVID-19 Vaccine

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Jul 3

PMID 34215591

Citations 51

Authors

Dong An

Kun Li

Dawne K Rowe

Maria Cristina Huertas Diaz

Emily F Griffin

Ashley C Beavis

Scott K Johnson

Ian Padykula

Cheryl A Jones

Kelsey Briggs

Geng Li

Yuan Lin

Jiachen Huang

Jarrod Mousa

Melinda Brindley

Kaori Sakamoto

David K Meyerholz

Paul B McCray Jr

S Mark Tompkins

Biao He

Affiliations

Soon will be listed here.

Abstract

Transmission-blocking vaccines are urgently needed to reduce transmission of SARS-CoV 2, the cause of the COVID-19 pandemic. The upper respiratory tract is an initial site of SARS-CoV-2 infection and, for many individuals, remains the primary site of virus replication. An ideal COVID-19 vaccine should reduce upper respiratory tract virus replication and block transmission as well as protect against severe disease. Here, we optimized a vaccine candidate, parainfluenza virus 5 (PIV5) expressing the SARS-CoV-2 S protein (CVXGA1), and then demonstrated that a single-dose intranasal immunization with CVXGA1 protects against lethal infection of K18-hACE2 mice, a severe disease model. CVXGA1 immunization also prevented virus infection of ferrets and blocked contact transmission. This mucosal vaccine strategy inhibited SARS-CoV-2 replication in the upper respiratory tract, thus preventing disease progression to the lower respiratory tract. A PIV5-based mucosal vaccine provides a strategy to induce protective innate and cellular immune responses and reduce SARS-CoV-2 infection and transmission in populations.

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References

Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C, Abiona O . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483):1260-1263. PMC: 7164637. DOI: 10.1126/science.abb2507. View

Phan S, Zengel J, Wei H, Li Z, Wang D, He B . Parainfluenza Virus 5 Expressing Wild-Type or Prefusion Respiratory Syncytial Virus (RSV) Fusion Protein Protects Mice and Cotton Rats from RSV Challenge. J Virol. 2017; 91(19). PMC: 5599740. DOI: 10.1128/JVI.00560-17. View

Amanat F, Stadlbauer D, Strohmeier S, Nguyen T, Chromikova V, McMahon M . A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med. 2020; 26(7):1033-1036. PMC: 8183627. DOI: 10.1038/s41591-020-0913-5. View

Cornwell H, McCandlish I, Thompson H, Laird H, Wright N . Isolation of parainfluenza virus SV5 from dogs with respiratory disease. Vet Rec. 1976; 98(15):301-2. DOI: 10.1136/vr.98.15.301. View

Phan S, Chen Z, Xu P, Li Z, Gao X, Foster S . A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5). Vaccine. 2014; 32(25):3050-7. PMC: 4039636. DOI: 10.1016/j.vaccine.2014.03.049. View

Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M . Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020; 369(6499):77-81. PMC: 7202686. DOI: 10.1126/science.abc1932. View

Richard M, Kok A, de Meulder D, Bestebroer T, Lamers M, Okba N . SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nat Commun. 2020; 11(1):3496. PMC: 7343828. DOI: 10.1038/s41467-020-17367-2. View

Wolfel R, Corman V, Guggemos W, Seilmaier M, Zange S, Muller M . Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581(7809):465-469. DOI: 10.1038/s41586-020-2196-x. View

Mooney A, Li Z, Gabbard J, He B, Tompkins S . Recombinant parainfluenza virus 5 vaccine encoding the influenza virus hemagglutinin protects against H5N1 highly pathogenic avian influenza virus infection following intranasal or intramuscular vaccination of BALB/c mice. J Virol. 2012; 87(1):363-71. PMC: 3536407. DOI: 10.1128/JVI.02330-12. View

10.

Li N, Wang X, Lv T . Prolonged SARS-CoV-2 RNA shedding: Not a rare phenomenon. J Med Virol. 2020; 92(11):2286-2287. PMC: 7267144. DOI: 10.1002/jmv.25952. View

11.

McCray Jr P, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L . Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol. 2006; 81(2):813-21. PMC: 1797474. DOI: 10.1128/JVI.02012-06. View

12.

Zheng J, Wong L, Li K, Verma A, Ortiz M, Wohlford-Lenane C . COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice. Nature. 2020; 589(7843):603-607. PMC: 7855185. DOI: 10.1038/s41586-020-2943-z. View

13.

Chen Z, Xu P, Salyards G, Harvey S, Rada B, Fu Z . Evaluating a parainfluenza virus 5-based vaccine in a host with pre-existing immunity against parainfluenza virus 5. PLoS One. 2012; 7(11):e50144. PMC: 3502407. DOI: 10.1371/journal.pone.0050144. View

14.

Meyerholz D, Beck A . Principles and approaches for reproducible scoring of tissue stains in research. Lab Invest. 2018; 98(7):844-855. DOI: 10.1038/s41374-018-0057-0. View

15.

Winkler E, Bailey A, Kafai N, Nair S, McCune B, Yu J . SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function. Nat Immunol. 2020; 21(11):1327-1335. PMC: 7578095. DOI: 10.1038/s41590-020-0778-2. View

16.

van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham J, Port J . ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020; 586(7830):578-582. PMC: 8436420. DOI: 10.1038/s41586-020-2608-y. View

17.

Corbett K, Flynn B, Foulds K, Francica J, Boyoglu-Barnum S, Werner A . Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N Engl J Med. 2020; 383(16):1544-1555. PMC: 7449230. DOI: 10.1056/NEJMoa2024671. View

18.

Mooney A, Gabbard J, Li Z, Dlugolenski D, Johnson S, Tripp R . Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge. J Virol. 2017; 91(23). PMC: 5686712. DOI: 10.1128/JVI.01579-17. View

19.

Wang H, Zhang Y, Huang B, Deng W, Quan Y, Wang W . Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell. 2020; 182(3):713-721.e9. PMC: 7275151. DOI: 10.1016/j.cell.2020.06.008. View

20.

Kim Y, Kim S, Kim S, Kim E, Park S, Yu K . Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020; 27(5):704-709.e2. PMC: 7144857. DOI: 10.1016/j.chom.2020.03.023. View