Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination.
Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination.
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DOI：
10.1126/sciimmunol.add4853
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发表时间：
2022-10-28
影响因子：
24.8
通讯作者：
中科院分区：
文献类型：
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作者：
SARS-CoV-2 mRNA疫苗接种在循环中诱导强大的体液和细胞免疫;然而，目前尚不清楚它是否在呼吸道中产生有效的免疫应答，特别是针对关注的变体（VOC），包括Omicron。我们比较了接种COVID-19疫苗的个体和住院患者的支气管肺泡灌洗液（BAL）和血液中SARS-CoV-2 S特异性总抗体和中和抗体应答，以及B和T细胞免疫。与COVID-19恢复期患者相比，接种疫苗的个体BAL中针对D 614 G、Delta（B.1.617.2）和Omicron BA.1.1的中和抗体水平显著较低，尽管血液中存在强烈的S特异性抗体应答。此外，mRNA疫苗接种诱导了循环S特异性B和T细胞免疫，但与COVID-19恢复期相比，接种疫苗个体的BAL中不存在这些应答。使用小鼠免疫模型，我们证明了单独的全身性mRNA疫苗接种诱导弱的呼吸道粘膜中和抗体应答，特别是针对小鼠中的SARS-CoV-2 Omicron BA.1.1;然而，全身性mRNA疫苗接种加粘膜腺病毒-S免疫的组合诱导强的中和抗体应答，不仅针对祖先病毒，还针对Omicron BA.1.1变体。总之，我们的研究支持了这样一种论点，即目前的COVID-19疫苗对严重疾病的发展非常有效，可能是通过在再感染期间招募循环B和T细胞应答，但对突破性感染提供的保护有限，特别是Omicron亚系。因此，需要粘膜加强疫苗接种以在呼吸道中建立针对SARS-CoV-2的强大的杀菌免疫，包括Omicron亚系和未来VOC的感染。COVID-19 mRNA疫苗诱导的抗Omicron粘膜免疫力较差，但这种免疫力可以通过鼻内免疫增强。
SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19 vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2) and Omicron BA.1.1 in the BAL compared to COVID-19 convalescents, despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses, not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during re-infection, but offer limited protection against breakthrough infection, especially by Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by Omicron sublineage and future VOCs. COVID-19 mRNA vaccines induce poor anti-Omicron mucosal immunity, but this immunity can boosted with an intranasal immunization.
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