ABSTRACT

Although unprecedented efforts aiming to stop the COVID-19 pandemic have been made over the past two years, SARSCoV-2 virus still continues to cause intolerable health and economical losses. Vaccines are considered the most effective way to prevent infectious diseases, which has been reaffirmed for COVID-19. However, in the context of the continuing virus spread because of insufficient vaccination coverage and emergence of new variants of concern, there is a high demand for vaccination strategy amendment. The ability to elicit protective immunity at the entry gates of infection provided by mucosal vaccination is key to block virus infection and transmission. Therefore, these mucosal vaccines are believed to be a “silver bullet” that could bring the pandemic to an end. Here, we demonstrate that the intranasally delivered Gam-COVID-Vac (Sputnik V) vaccine induced a robust (no less than 180 days) systemic and local immune response in mice. High immunogenic properties of the vaccine were verified in non-human primates (common marmosets) by marked IgG and neutralizing antibody (NtAb) production in blood serum, antigen-specific Tcell proliferation and cytokine release of peripheral blood mononuclear cells accompanied by formation of IgA antibodies in the nasal mucosa. We also demonstrate that Sputnik V vaccine can provide sterilizing immunity in K18-hACE2 transgenic mice exposed to experimental lethal SARS-CoV-2 infection protecting them against severe lung immunopathology and mortality. We believe that intranasal Sputnik V vaccine is a promising novel needle-free mucosal vaccine candidate for primary immunization as well as for revaccination and is worth further clinical investigation.

摘要

尽管在过去两年中为阻止 COVID-19 大流行做出了前所未有的努力，但 SARSCoV-2 病毒仍然继续造成无法忍受的健康和经济损失。疫苗被认为是预防传染病的最有效方法，这一点已在 COVID-19 中得到重申。然而，在由于疫苗接种覆盖率不足和新变种出现而导致病毒持续传播的背景下，对疫苗接种策略的修改提出了很高的要求。粘膜疫苗提供的在感染入口处引发保护性免疫的能力是阻止病毒感染和传播的关键。因此，这些黏膜疫苗被认为是可以结束大流行的“灵丹妙药”。这里，我们证明，鼻内递送的 Gam-COVID-Vac (Sputnik V) 疫苗在小鼠体内诱导了强烈的（不少于 180 天）全身和局部免疫反应。通过血清中显着的 IgG 和中和抗体 (NtAb) 的产生、抗原特异性 T 细胞增殖和外周血单核细胞的细胞因子释放以及 IgA 抗体的形成，验证了该疫苗在非人灵长类动物（普通狨猴）中的高免疫原性在鼻粘膜中。我们还证明，Sputnik V 疫苗可以在暴露于实验性致死性 SARS-CoV-2 感染的 K18-hACE2 转基因小鼠中提供灭菌免疫，保护它们免受严重的肺部免疫病理学和死亡率的影响。