Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection.

Sang Heui Seo,Yunyueng Jang

doi:10.3390/vaccines8040584

Sang Heui Seo, Yunyueng Jang

Open Access

https://doi.org/10.3390/vaccines8040584

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Journal: Vaccines	Publication Date: Oct 3, 2020
Citations: 70	License type: CC BY 4.0

Affiliation: Daejeon University, Chungnam National University

Abstract

A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe a cold-adapted live-attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22 °C/2020) developed by gradually adapting the growth of SARS-CoV-2 from 37 °C to 22 °C in Vero cells. This vaccine can be potentially administered to humans as a nasal spray. Its single dose strongly induced neutralising antibodies (titre > 640), cellular immunity, and mucosal IgA antibodies in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infections. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show body weight loss, death, or the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. These results demonstrate that the cold-adapted live attenuated SARS-CoV-2 vaccine we have developed may be a candidate SARS-CoV-2 vaccine for humans.

Highlights

In December 2019, human cases of mysterious severe pneumonia were reported from the city of Wuhan in eastern China [1,2]
To develop a live attenuated vaccine for Severe Acute Respiratory Syndrome (SARS)-CoV-2, amenable to intranasal delivery, we gradually adapted SARS-CoV-2 isolated from a human patient (SARS-CoV-2/human/Korea/CNUHV03/2020; referred to as CoV-2-CNUHV03 in this study) (GenBank accession number: MT678839) [35] to a temperature from 37 ◦ C to 22 ◦ C in Vero cells cultured in an atmosphere of 5% CO2 in a humidified incubator
When cells infected with SARS-CoV-2 showed complete cytopathic effects (CPE) at the set temperature, they were incubated at the lower temperature

Summary

Introduction

In December 2019, human cases of mysterious severe pneumonia were reported from the city of Wuhan in eastern China [1,2]. The initial symptoms were found to be similar to those of patients infected with Severe Acute Respiratory Syndrome (SARS) virus. Sequencing of the causative agent showed that its genome was similar to that of SARS, leading to its designation as Severe Acute. Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) [1,2]. Declared coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, as a pandemic on 11 March 2020. SARS-CoV-2 belongs to the family of coronaviruses, which are enveloped, positive-sense single-stranded RNA viruses [3]. The genome size of SARS-CoV-2 is about 30 kb. SARS-CoV-2 consists of four structural proteins, namely nucleocapsid (N), membrane (M), envelope (E), and spike (S)

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Conclusion