Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
Immunol Cell Biol. 2023 Nov-Dec;101(10):975-983. doi: 10.1111/imcb.12685. Epub 2023 Sep 5.
Mucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS-CoV-2 variants of concern (VoCs). Here, we profiled paired mucosal (saliva, tears) and plasma antibodies from COVID-19 vaccinated only vaccinees (uninfected, vaccinated) and COVID-19 recovered vaccinees (COVID-19 recovered, vaccinated) who both received Vaxzevria vaccines. SARS-CoV-2 ancestral-specific IgG antibodies capable of engaging FcγR3a were significantly higher in the mucosal samples of COVID-19 recovered Vaxzevria vaccinees in comparison with vaccinated only vaccinees. However, when IgG and FcγR3a engaging antibodies were tested against a panel of SARS-CoV-2 VoCs, the responses were ancestral-centric with weaker recognition of Omicron strains observed. In contrast, salivary IgA, but not plasma IgA, from Vaxzevria vaccinees displayed broad cross-reactivity across all SARS-CoV-2 VoCs tested. Our data highlight that while intramuscular Vaxzevria vaccination can enhance mucosal antibodies responses in COVID-19 recovered vaccinees, restrictions by ancestral-centric bias may have implications for COVID-19 protection. However, highly cross-reactive mucosal IgA could be key in addressing these gaps in mucosal immunity and may be an important focus of future SARS-CoV-2 vaccine development.
黏膜抗体在预防突破性 COVID-19 感染和新兴病毒变体方面发挥着关键作用。基于肌肉内腺病毒的疫苗（Vaxzevria）仅能微弱地诱导鼻内 IgG 和 IgA 反应，除非疫苗接种者之前曾被感染过。然而，人们对 Vaxzevria 疫苗接种如何影响黏膜抗体诱导 Fc 反应的能力知之甚少，特别是针对 SARS-CoV-2 关注的变体（VOCs）。在这里，我们对仅接受过 COVID-19 疫苗接种（未感染、已接种）和 COVID-19 康复疫苗接种者（COVID-19 康复、已接种）的配对黏膜（唾液、眼泪）和血浆抗体进行了分析，他们都接种了 Vaxzevria 疫苗。与仅接种疫苗的疫苗接种者相比，COVID-19 康复的 Vaxzevria 疫苗接种者的黏膜样本中，能够与 FcγR3a 结合的 SARS-CoV-2 原始特异性 IgG 抗体明显更高。然而，当 IgG 和 FcγR3a 结合抗体针对一组 SARS-CoV-2 VOCs 进行测试时，反应以原始为中心，观察到对奥密克戎株的识别较弱。相比之下，来自 Vaxzevria 疫苗接种者的唾液 IgA，但不是血浆 IgA，显示出对所有测试的 SARS-CoV-2 VOC 的广泛交叉反应性。我们的数据表明，虽然肌肉内 Vaxzevria 疫苗接种可以增强 COVID-19 康复疫苗接种者的黏膜抗体反应，但以原始为中心的偏倚限制可能对 COVID-19 保护产生影响。然而，高度交叉反应性的黏膜 IgA 可能是解决黏膜免疫这些差距的关键，并且可能是未来 SARS-CoV-2 疫苗开发的重要重点。
