Tang Ying, Boribong Brittany P, Swank Zoe N, Demokritou Melina, Luban Maria A F, Fasano Alessio, Du Michelle, Wolf Rebecca L, Griffiths Joseph, Shultz John, Borberg Ella, Chalise Sujata, Gonzalez Wanda I, Walt David R, Yonker Lael M, Horwitz Bruce H
Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
Harvard Medical School, Boston, MA 02115, USA.
medRxiv. 2024 Apr 16:2024.04.15.24305767. doi: 10.1101/2024.04.15.24305767.
Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children.
We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples, N=116) or on convenience samples of children under 5 years of age presenting to a pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation.
Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process.
Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.
了解对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗接种的抗体反应对于完善2019冠状病毒病（COVID-19）免疫策略至关重要。产生包括黏膜免疫球蛋白A（IgA）在内的黏膜免疫反应可能对疫苗效力有潜在益处，但关于目前给幼儿接种信使核糖核酸（mRNA）疫苗后黏膜抗体产生的证据有限。
我们测量了一组5岁以下接受SARS-CoV-2 mRNA疫苗接种儿童（连续收集的匹配血清和唾液样本，N = 116）或到儿科急诊科就诊的5岁以下儿童便利样本（鼻拭子，N = 103）中针对SARS-CoV-2的抗体水平。此外，我们评估了唾液和鼻样本诱导SARS-CoV-2刺突介导的中性粒细胞胞外陷阱（NET）形成的能力。
对疫苗接种后唾液反应的纵向分析显示诱导产生了SARS-CoV-2特异性免疫球蛋白G（IgG），但未诱导产生IgA。同样，仅在有或无疫苗接种史的既往感染儿童的鼻样本中观察到SARS-CoV-2特异性IgA，而在无感染史的接种疫苗儿童中未观察到。此外，从既往感染儿童获得的口咽样本能够触发增强的刺突介导的NET形成，并且IgA在驱动这一过程中起关键作用。
尽管在口鼻黏膜中诱导产生了特异性IgG，但目前的肌内注射疫苗在幼儿中产生黏膜IgA的能力有限。这些结果证实了mRNA疫苗接种后黏膜IgA反应与全身体液反应的独立性，并提示了未来可能增强该幼儿年龄组黏膜保护的疫苗接种策略。
