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<p><b>The aim of the work.</b> 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 range of other SARS-CoV-2 variants. <b>Materials and methods.</b> A recombinant Sendai virus with transgene S(JN.1) insertion between the <i>P</i> and <i>M</i> 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. <b>Results.</b> 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 variants. The 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<sup>6</sup> 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. <b>Conclusions.</b> 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 lineage.</p>

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Cross-Neutralizing Activity of a Live Intranasal Vaccine Based on the Recombinant Sendai Virus of the Moscow Strain against Different Variants of SARS-CoV-2

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • G. A. Kudrov,
  • S. S. Zainutdinov,
  • A. V. Zaykovskaya,
  • I. S. Shulgina,
  • A. A. Grazhdantseva,
  • G. F. Sivolobova,
  • S. A. Bodnev,
  • A. A. Sergeev,
  • G. V. Kochneva

摘要

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 range 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 variants. The 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 106 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. Conclusions. 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 lineage.