背景:由于鼻粘膜是COVID-19的初始感染部位,因此鼻内疫苗比常规疫苗更有利。在最近的临床研究中,鼻内免疫已显示产生更高的中和抗体;然而,缺乏上气道灭菌免疫的证据。以前,我们开发了编码SARS-CoV-2(rMeV-S)刺突蛋白的重组麻疹病毒,引发针对SARS-CoV-2的体液和细胞免疫应答。
目的:在本研究中,我们的目标是提供一项针对麻疹病毒平台和注射途径的鼻疫苗实验。
方法:制备表达rMeV-S的重组麻疹病毒,并通过肌内或鼻内注射对叙利亚金仓鼠施用5×105PFU的rMeV-S。随后,仓鼠用1×105PFU的SARS-CoV-2接种并在感染后4天安乐死。测定血清中的中和抗体和RBD特异性IgG以及支气管肺泡灌洗液(BALF)中的RBD特异性IgA,通过定量逆转录PCR(qRT-PCR)分析和上呼吸道和肺中的病毒滴度测量来确定SARS-CoV-2的清除能力。对来自实验仓鼠的肺样品进行免疫组织化学和组织病理学检查。
结果:rMeV-S的鼻内免疫引发保护性免疫反应,减轻病毒诱导的病理生理学,例如仓鼠的体重减少和肺重量增加。此外,肺免疫组织化学表明,鼻内rMeV-S免疫诱导有效的SARS-CoV-2清除,与病毒RNA含量相关,通过qRT-PCR确定,在肺部和鼻腔冲洗样本中,肺部SARS-CoV-2病毒滴度,洗鼻器,BALF样本,血清RBD特异性IgG浓度,和BALF中RBD特异性IgA浓度。
结论:由于典型的病毒感染途径,基于麻疹病毒平台的鼻内疫苗是一种有前途的策略,疫苗管理的便利性,以及它引发的强烈免疫反应。
As the nasal mucosa is the initial site of infection for COVID-19, intranasal vaccines are more favorable than conventional vaccines. In recent clinical studies, intranasal immunization has been shown to generate higher neutralizing antibodies; however, there is a lack of evidence on sterilizing immunity in the upper airway. Previously, we developed a recombinant measles virus encoding the spike protein of SARS-CoV-2 (rMeV-S), eliciting humoral and cellular immune responses against SARS-CoV-2.
In this study, we aim to provide an experiment on nasal vaccines focusing on a measles virus platform as well as injection routes.
Recombinant measles viruses expressing rMeV-S were prepared, and 5 × 105 PFUs of rMeV-S were administered to Syrian golden hamsters via intramuscular or intranasal injection. Subsequently, the hamsters were challenged with inoculations of 1 × 105 PFUs of SARS-CoV-2 and euthanized 4 days post-infection. Neutralizing antibodies and RBD-specific IgG in the serum and RBD-specific IgA in the bronchoalveolar lavage fluid (BALF) were measured, and SARS-CoV-2 clearance capacity was determined via quantitative reverse-transcription PCR (qRT-PCR) analysis and viral titer measurement in the upper respiratory tract and lungs. Immunohistochemistry and histopathological examinations of lung samples from experimental hamsters were conducted.
The intranasal immunization of rMeV-S elicits protective immune responses and alleviates virus-induced pathophysiology, such as body weight reduction and lung weight increase in hamsters. Furthermore, lung immunohistochemistry demonstrated that intranasal rMeV-S immunization induces effective SARS-CoV-2 clearance that correlates with viral RNA content, as determined by qRT-PCR, in the lung and nasal wash samples, SARS-CoV-2 viral titers in lung, nasal wash, BALF samples, serum RBD-specific IgG concentration, and RBD-specific IgA concentration in the BALF.
An intranasal vaccine based on the measles virus platform is a promising strategy owing to the typical route of infection of the virus, the ease of administration of the vaccine, and the strong immune response it elicits.