Barrett Edward G, Revelli David, Bakshi Chandra Shekhar, Kadish Alan, Amar Salomon
Lovelace Biomedical Research Institute, Albuquerque, NM, United States.
Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States.
Front Microbiol. 2023 May 24;14:1212179. doi: 10.3389/fmicb.2023.1212179. eCollection 2023.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in over 6.7 million deaths worldwide. COVID-19 vaccines administered parenterally via intramuscular or subcutaneous (SC) routes have reduced the severity of respiratory infections, hospitalization rates, and overall mortality. However, there is a growing interest in developing mucosally delivered vaccines to further enhance the ease and durability of vaccination. This study compared the immune response in hamsters immunized with live SARS-CoV-2 virus via SC or intranasal (IN) routes and assessed the outcome of a subsequent IN SARS-CoV-2 challenge. Results showed that SC-immunized hamsters elicited a dose-dependent neutralizing antibody response but of a significantly lower magnitude than that observed in IN-immunized hamsters. The IN challenge with SARS-CoV-2 in SC-immunized hamsters resulted in body weight loss, increased viral load, and lung pathology than that observed in IN-immunized and IN-challenged counterparts. These results demonstrate that while SC immunization renders some degree of protection, IN immunization induces a stronger immune response and better protection against respiratory SARS-CoV-2 infection. Overall, this study provides evidence that the route of primary immunization plays a critical role in determining the severity of a subsequent respiratory infection caused by SARS-CoV-2. Furthermore, the findings suggest that IN route of immunization may be a more effective option for COVID-19 vaccines than the currently used parenteral routes. Understanding the immune response to SARS-CoV-2 elicited via different immunization routes may help guide more effective and long-lasting vaccination strategies.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒引起的2019冠状病毒病大流行已导致全球超过670万人死亡。通过肌肉注射或皮下注射途径进行肠胃外给药的2019冠状病毒病疫苗降低了呼吸道感染的严重程度、住院率和总体死亡率。然而，人们对开发粘膜给药疫苗的兴趣日益浓厚，以进一步提高疫苗接种的便利性和持久性。本研究比较了通过皮下或鼻内途径用活SARS-CoV-2病毒免疫的仓鼠的免疫反应，并评估了随后鼻内感染SARS-CoV-2的结果。结果显示，皮下免疫的仓鼠引发了剂量依赖性中和抗体反应，但幅度明显低于鼻内免疫的仓鼠。皮下免疫的仓鼠接受SARS-CoV-2鼻内攻击后，与鼻内免疫并接受鼻内攻击的仓鼠相比，体重减轻、病毒载量增加且出现肺部病变。这些结果表明，虽然皮下免疫提供了一定程度的保护，但鼻内免疫诱导了更强的免疫反应，并能更好地预防呼吸道SARS-CoV-2感染。总体而言，本研究提供了证据，即初次免疫途径在决定随后由SARS-CoV-2引起的呼吸道感染的严重程度方面起着关键作用。此外，研究结果表明，对于2019冠状病毒病疫苗，鼻内免疫途径可能比目前使用的肠胃外途径更有效。了解通过不同免疫途径对SARS-CoV-2引发的免疫反应可能有助于指导更有效和持久的疫苗接种策略。
