A Scalable Topical Vectored Vaccine Candidate against SARS-CoV-2.

Mohammed A Rohaim,Muhammad Munir

doi:10.3390/vaccines8030472

Mohammed A Rohaim, Muhammad Munir

Open Access

https://doi.org/10.3390/vaccines8030472

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Journal: Vaccines	Publication Date: Aug 24, 2020
Citations: 23	License type: CC BY 4.0

Affiliation: Lancaster University

Abstract

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of a SARS-CoV-2 vaccine which would be safe, efficacious and scalable. Owing to unavailability of the vaccine, we propose a de novo synthesized avian orthoavulavirus 1 (AOaV-1)-based topical respiratory vaccine candidate against CoVID-19. Avirulent strain of AOaV-1 was engineered to express full length spike (S) glycoprotein which is highly neutralizing and a major protective antigen of the SARS-CoV-2. Broad-scale in vitro characterization of a recombinant vaccine candidate demonstrated efficient co-expression of the hemagglutinin-neuraminidase (HN) of AOaV-1 and S protein of SARS-CoV-2, and comparable replication kinetics were observed in a cell culture model. The recombinant vaccine candidate virus actively replicated and spread within cells independently of exogenous trypsin. Interestingly, incorporation of S protein of SARS-CoV-2 into the recombinant AOaV-1 particles attributed the sensitivity to anti-SARS-CoV-2 antiserum and more prominently to anti-AOaV-1 antiserum. Finally, our results demonstrated that the recombinant vaccine vector stably expressed S protein after multiple propagations in chicken embryonated eggs, and this expression did not significantly impact the in vitro growth characteristics of the recombinant. Taken together, the presented respiratory vaccine candidate is highly attenuated in primates per se, safe and lacking pre-existing immunity in human, and carries the potential for accelerated vaccine development against CoVID-19 for clinical studies.

Highlights

An outbreak of pneumonia erupted in a Chinese seafood market in Wuhan during late 2019 and within a month of its origin, on 30 January 2020, a Public Health Emergency of InternationalConcern was declared by the World Health Organization (WHO) due to its high human-to-human transmission
The construct was named rAOaV-1-SARS-CoV-2 whereas the avian orthoavulavirus 1 (AOaV-1) without the insertion of the foreign gene (AOaV-1-wt) was used as infection control throughout the study
S gene was codon-optimized for Homo sapiens codon usage and inserted into the unique PmeI site between the P and M genes, which was originally preserved during the cloning of complete antigenome (Figure 1A)

Summary

Introduction

An outbreak of pneumonia erupted in a Chinese seafood market in Wuhan during late 2019 and within a month of its origin, on 30 January 2020, a Public Health Emergency of InternationalConcern was declared by the World Health Organization (WHO) due to its high human-to-human transmission. An outbreak of pneumonia erupted in a Chinese seafood market in Wuhan during late 2019 and within a month of its origin, on 30 January 2020, a Public Health Emergency of International. The outbreak of coronavirus disease in 2019 (CoVID-19) soared among communities unprecedentedly and spread across the globe and a pandemic was declared on 11 March 2020 by the WHO. A large proportion (~80%) of CoVID-19 infected patients showed only moderate symptoms which led to a staggering rate increase in the global spread of the infection. The acute respiratory distress syndrome, manifested in ~20% of CoVID-19 patients, causing substantial case fatality rates especially in elderly and frail people with co-morbidities [1,2]. The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing CoVID-19 pandemic, belongs to the family Coronavirdae within the Betacoronavirus (β-CoV) genus. Similar to SARS-CoV and Middle Eastern respiratory syndrome-related coronavirus (MERS-CoV), SARS-CoV-2 carries a single stranded linear RNA genome with positive polarity [3]

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