THE AIM OF THE WORK
Design and investigation the properties of a prototype for a single intranasal vaccine based on a recombinant Sendai virus Moscow strain expressing as an immunogen the S protein of the JN.1 variant, and an assessment of its cross-activity against a number of other SARS-CoV-2 variants.
MATERIALS AND METHODS
A recombinant Sendai virus with transgene S(JN.1) insertion between the P and M genes was obtained by genetic engineering and RT-PCR. Expression of the transgene S(JN.1) was analyzed by immunoblotting. The immunogenicity of the vaccine construct was evaluated by ELISA and virus-neutralization assays in BALB/c mice. The protection was assessed in K18-hACE2 mice by the level of reduced replication (quantitative RT-PCR) and the decrease in the infection titer (on Vero E6 cells) of SARS-CoV-2 in the tissues of the nasal cavity and lungs of vaccinated animals.
RESULTS
Based on the Moscow strain of the Sendai virus, the vaccine construct Sen-S-JN.1(M) has been developed, which expresses the S protein of the circulating variant JN.1 of SARS-CoV-2. It has been shown that S protein is effectively exposed on Sen-S-JN.1(M) virions and induces the formation of a mucosal and systemic humoral immune response against SARS-CoV-2 variant JN.1 during a single intranasal vaccination of BALB/c mice. Analysis of the cross-neutralizing activity revealed a significant decrease in antibody titers against variants Delta, BA.1, XBB.1.5 and EG.5.1 while maintaining a high level of neutralization against XBB.1.16 and BA.5.2 options. K18-hACE2 mice vaccinated with Sen-S-JN.1(M) were well protected from SARS-CoV-2 (JN.1) infection due to a significant (more than 10^6-fold) reduction in viral replicative activity. None of the lung and turbinate samples from the vaccinated mice contained detectable levels of infectious SARS-CoV-2, which indicates that the infection had stopped.
CONCLUSION
The recombinant virus Sen-S-JN.1(M) is a promising vaccine construct and can provide cross-protection against circulating and evolutionarily similar variants of the SARS-CoV-2 Omicron line.
