A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

Key Words:Immunology, Vaccine 

Research Highlights 

1. Pre-clinical evaluation of an egg-based inactivated Newcastle disease virus (NDV) chimera stably expressing the membrane-anchored form of the spike (NDV-S) is shown to elicit potent protection against COVID-19 vaccine in mice and hamsters 

2. NDV-S is immunogenic and either protected animals from SARS-CoV-2 infections or significantly attenuated induced disease  

Summary  

The study explores the potential use of NDV-based vector expressing a pre-fusion spike protein. The NDV vector, based on an Influenza vaccine virus strain against an avian pathogen, overcomes many limitations of other vaccine candidates in terms of production and scaling and allows to utilise the existing global egg-based production capacity for inactivated influenza virus vaccines to rapidly produce NDV-S vaccine with minimal modifications to their production pipelines. Using mice and hamster as models, two doses of the recombinant attenuated NDV vector expressing the membrane-anchored form of the spike (NDV-S) elicits immunogenic responses including humoral responses with neutralization activity. Impotently, the vaccinated animals were protected from SARS-CoV-2 infection or SARS-CoV-2 induced disease. Combining the vaccine with an adjuvant (DOTAP liposomes or Addavax emulsion) is shown to result in dose sparing. The vaccine protects mice from infected by mouse-adapted SARS-CoV-2 and to confer protection against infection in a Golden Syrian hamster model. 

• In vivo study (e.g. mouse, NHP)  

Strengths and limitations of the paper 

Novelty: First pre-clinical results of the novel NDV-S vaccine candidate which has an advantage of large-scale production at low cost and has a good safety profile in infants, pregnant women and the elderly (Langley JM et al, 2015; Madan A et al, 2017) 

Standing in the field: Offers certain advantages over other vaccine candidates in terms of production 

Appropriate statistics: There is no statistical analysis or comparison 

Viral model used:Mouse-adapted and human SARS-CoV-2 

Translatability:The study proposing egg-based NDV-S vaccine as candidate SARS-CoV-2 vaccines. 

Main limitations:  

1. Proof of principle study with little statistics and no comparison to other, already reported vaccine results 

2. The study evaluated the adjuvant R-DOTAP in mice model only with no data reported for adjuvant R-DOTAP in hamsters. However, the authors justify that with the dosing of adjuvant R-DOTAP was not well determined for their hamster model by the time of this study. 

3. As authors noted, minimal evidence was reported for outcomes of SARS-CoV-2 induced disease in hamsters, such as viral titers in nasal washes or lungs. 

4. While the level of serum antibody responses against Spike protein was evaluated, no evaluation was reported for T cell immunity in this study, given that the antibody responses might wane with time and B cells tend to be short lived in SARS-CoV-1 infection (Channappanavar et al., 2014; Tang et al., 2011)