Development of an intranasal vaccine against COVID-19

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the COVID-19 pandemic. Rapid spread of the disease repeatedly overloaded the public health sector and severely affects the global economy. Vaccines that protect against this disease were urgently needed. We developed a candidate intra-nasal COVID-19 vaccine based on a Newcastle disease virus (NDV) vector that expresses the immunogenic spike (S) protein of SARS-CoV-2. We have generated four different recombinant NDV-S vaccine candidates. Three were evaluated in a vaccination and challenge model in hamsters, using either intra-muscular injection or intra-nasal instillation as vaccination route. Two vaccine constructs showed accumulation of T-C hypermutation in their genome, and were rejected as vaccine candidates. The third construct, a recombinant NDV containing a codon-optimized open reading frame encoding the full-length spike protein obtained from the original SARS-CoV-2 Wuhan isolate, induced high neutralizing antibody responses and protected hamsters from intra-nasal SARS-CoV-2 challenge infection.

Immunogenicity, protective efficacy and inhibition of virus shedding from the upper respiratory tract appeared slightly higher if the vaccine was delivered intra-nasally as compared to injection. To address potential causes of hypermutation, one additional recombinant NDV was generated expressing the full-length S protein of the SARS-CoV-2 variant of concern delta, using the native sequence without codon optimization. This virus has been generated, did not contain hypermutation in passages 2 or 5, and was shown to induce S expression in infected cells. This NDV construct may be an interesting candidate for further evaluation as a candidate intra-nasal COVID-19 booster vaccine. 

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