Innovative Vaccine Research and Development Center, The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan.
Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Front Immunol. 2023 Aug 31;14:1224634. doi: 10.3389/fimmu.2023.1224634. eCollection 2023.
Vaccinations are ideal for reducing the severity of clinical manifestations and secondary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, SARS-CoV-2 continues to cause morbidity and mortality worldwide. In contrast to parenteral vaccines such as messenger RNA vaccines, nasal vaccines are expected to be more effective in preventing viral infections in the upper respiratory tract, the primary locus for viral infection and transmission. In this study, we examined the prospects of an inactivated whole-virion (WV) vaccine administered intranasally against SARS-CoV-2.
Mice were immunized subcutaneously (subcutaneous vaccine) or intranasally (nasal vaccine) with the inactivated WV of SARS-CoV-2 as the antigen.
The spike protein (S)-specific IgA level was found to be higher upon nasal vaccination than after subcutaneous vaccination. The level of S-specific IgG in the serum was also increased by the nasal vaccine, although it was lower than that induced by the subcutaneous vaccine. The nasal vaccine exhibited a stronger defense against viral invasion in the upper respiratory tract than the subcutaneous vaccine and unimmunized control; however, both subcutaneous and nasal vaccines provided protection in the lower respiratory tract. Furthermore, we found that intranasally administered inactivated WV elicited robust production of S-specific IgA in the nasal mucosa and IgG in the blood of mice previously vaccinated with messenger RNA encoding the S protein.
Overall, these results suggest that a nasal vaccine containing inactivated WV can be a highly effective means of protection against SARS-CoV-2 infection.
接种疫苗是减轻严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）临床症状和继发并发症严重程度的理想方法；然而，SARS-CoV-2 仍在全球范围内导致发病和死亡。与信使 RNA 疫苗等注射疫苗相比，鼻腔疫苗有望在预防上呼吸道病毒感染方面更有效，而上呼吸道是病毒感染和传播的主要部位。在这项研究中，我们研究了经鼻腔接种的 SARS-CoV-2 灭活全病毒（WV）疫苗的前景。
用 SARS-CoV-2 的灭活 WV 作为抗原，通过皮下（皮下疫苗）或鼻腔（鼻腔疫苗）免疫小鼠。
鼻腔免疫后的 S 蛋白（S）特异性 IgA 水平高于皮下免疫。血清中 S 特异性 IgG 水平也因鼻腔疫苗而增加，尽管其水平低于皮下疫苗。鼻腔疫苗对呼吸道上部的病毒入侵具有更强的防御作用，而皮下疫苗和未免疫对照则没有；然而，皮下和鼻腔疫苗都能在下呼吸道提供保护。此外，我们发现，先前用编码 S 蛋白的信使 RNA 免疫的小鼠，经鼻腔给予灭活 WV 后，可在鼻黏膜中产生强烈的 S 特异性 IgA 反应，并在血液中产生 IgG。
总的来说，这些结果表明，含有灭活 WV 的鼻腔疫苗可能是预防 SARS-CoV-2 感染的一种非常有效的方法。
