Abstract
Rapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine candidate based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here, we show that the NDV vector expressing an optimized spike antigen (NDV-HXP-S) is a versatile vaccine inducing protective antibody responses. NDV-HXP-S can be administered intramuscularly as inactivated vaccine or intranasally as live vaccine. We show that NDV-HXP-S GMP-produced in Vietnam, Thailand and Brazil is effective in the hamster model. Furthermore, we show that intramuscular vaccination with NDV-HXP-S reduces replication of tested variants of concerns in mice. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters.
Highlights
Rapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern
To ensure high immunogenicity of the spike antigen expressed by the Newcastle disease virus (NDV) vector, we improved the spike construct by introducing the prefusion stabilizing Hexa Pro (HXP) mutations that were identified and characterized in an earlier study[4]
Compared with the was measured against the (WT) NDV, the NDV-HXP-S showed an extra band between 160 kD and 260 kD below the L protein of the NDV that corresponds to the size of the uncleaved S0 (Fig. 1b)
Summary
Rapid development of COVID-19 vaccines has helped mitigating SARS-CoV-2 spread, but more equitable allocation of vaccines is necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. With North America and Europe having the highest vaccination rates, vaccine resources are much less accessible to developing countries in Latin America, Asia, and Africa[1] Such inequitable availability of vaccine delays prompt control of COVID-19 and increases the risk of additional variants to emerge. We have previously developed a Newcastle disease virus (NDV)-based COVID-19 vaccine, in which a membraneanchored spike protein is expressed on the surface of the NDV virion This NDV vector could be used either as a live vaccine or an inactivated vaccine[2,3]. This report realistically reflects the feasibility of manufacturing a large quantity of NDV-based COVID-19 vaccine since few modifications to the influenza virus vaccine manufacturing process are needed This estimation assumes the dose of the NDV-based vaccine required will match that of monovalent pandemic influenza vaccines (15 μg/0.5 mL), without adjusting for the potential antigen-sparing effect of adjuvants[5]. Vaccine trials with the inactivated vaccines have been started in Thailand (NCT04764422, HXP-GPOVac) and Vietnam (NCT04830800, COVIVAC) and the live vaccine is currently in clinical development in Mexico (NCT04871737, Patria)
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