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

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.

Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models

“…The S gene was cloned in a pre-optimized gene junction between phosphoprotein and matrix gene of NDV. As we demonstrated previously 33 , the rNDV-S replicated comparably to rNDV-WT in both cell culture and avian eggs and spreads within cells independently of exogenous trypsin, proposing a competitive vaccine candidate.…”

“…We have previously developed an NDV-based SARS-CoV-2 vaccine encoding a human codon optimized full length spike (S) protein of SARS-CoV-2 (rNDV-S) using reverse genetics 33 . rNDV-S replicated in chicken embryonated eggs and cultured cells to levels comparable to a recombinant wild-type NDV (rNDV-WT).…”

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

“…Notably, still many current candidate vaccine vectors seem to involve expression of the full-length SARS-CoV-2 S protein (WHO, 2020). In some chimeric or surrogate rhabdo- or paramyxoviruses proposed as vaccine candidates, including VSVΔG-S or Newcastle disease virus (NDV-S), functional S is even determining or extending viral spread and tropism, respectively (Case et al, 2020a; Rohaim and Munir, 2020; Sun et al, 2020a; Sun et al, 2020b; Yahalom-Ronen et al, 2020).…”

Immune response to COVID-19 infection: a double-edged sword

“…A mRNA-1273 vaccine, a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine which encodes the spike protein (S protein) of SARS-CoV-2 was able to enhance antibodies production against the viral spike protein following the second dose during phase I trial [79]. A vaccine vector under preparation consists of a newly synthesized avian ortho-avulavirus 1 (AOaV-1) carrying the spike glycoprotein and hemagglutinin-neuraminidase HN genes has promising results [80]. In Canada, a series of authorized clinical trials are under investigations including recombinant BCG vaccine VPM1002 that is undergoing phase 3 clinical trial, coronavirus-like particle CoVLP vaccine in phase 1 and IMM-101 in phase 3 trial [81].…”