Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Public Health Agency of Sweden, Solna, Sweden.
Front Immunol. 2024 Mar 15;15:1346749. doi: 10.3389/fimmu.2024.1346749. eCollection 2024.
Several novel vaccine platforms aim at mucosal immunity in the respiratory tract to block SARS-CoV-2 transmission. Standardized methods for mucosal sample collection and quantification of mucosal antibodies are therefore urgently needed for harmonized comparisons and interpretations across mucosal vaccine trials and real-world data.
Using commercial electrochemiluminescence antibody panels, we compared SARS-CoV-2 spike-specific IgA and IgG in paired saliva, nasal secretions, and serum from 1048 healthcare workers with and without prior infection.
Spike-specific IgA correlated well in nasal secretions and saliva (r>0.65, p<0.0001), but the levels were more than three-fold higher in nasal secretions as compared to in saliva (p<0.01). Correlations between the total population of spike-specific IgA and spike-specific secretory IgA (SIgA) were significantly stronger (p<0.0001) in nasal secretions (r=0.96, p<0.0001) as opposed to in saliva (r=0.77, p<0.0001), and spike-specific IgA correlated stronger (p<0.0001) between serum and saliva (r=0.73, p<0.001) as opposed to between serum and nasal secretions (r=0.54, p<0.001), suggesting transudation of monomeric spike specific IgA from the circulation to saliva. Notably, spike-specific SIgA had a markedly higher SARS-CoV-2 variant cross-binding capacity as compared to the total population of spike specific IgA and IgG in both nasal secretions, saliva and serum, (all p<0.0001), which emphasizes the importance of taking potential serum derived monomeric IgA into consideration when investigating mucosal immune responses.
Taken together, although spike-specific IgA can be reliably measured in both nasal secretions and saliva, our findings imply an advantage of higher levels and likely also a larger proportion of SIgA in nasal secretions as compared to in saliva. We further corroborate the superior variant cross-binding capacity of SIgA in mucosal secretions, highlighting the potential protective benefits of a vaccine targeting the upper respiratory tract.
几种新型疫苗平台旨在针对呼吸道黏膜免疫以阻止 SARS-CoV-2 传播。因此，迫切需要标准化的黏膜样本采集方法和黏膜抗体定量方法，以便在黏膜疫苗试验和真实世界数据中进行协调比较和解释。
我们使用商业电化学发光抗体试剂盒，比较了 1048 名医护人员中有无既往感染的配对唾液、鼻分泌物和血清中的 SARS-CoV-2 刺突特异性 IgA 和 IgG。
刺突特异性 IgA 在鼻分泌物和唾液中相关性较好（r>0.65，p<0.0001），但鼻分泌物中的水平比唾液中高三倍以上（p<0.01）。在鼻分泌物中，总刺突特异性 IgA 与刺突特异性分泌型 IgA（SIgA）之间的相关性更强（p<0.0001）（r=0.96，p<0.0001），而在唾液中则较弱（r=0.77，p<0.0001），并且血清和唾液之间的刺突特异性 IgA 相关性更强（p<0.0001）（r=0.73，p<0.001），而血清和鼻分泌物之间的相关性较弱（r=0.54，p<0.001），表明单体刺突特异性 IgA 从循环中透过渗出到唾液中。值得注意的是，与总刺突特异性 IgA 和 IgG 相比，鼻分泌物、唾液和血清中的刺突特异性 SIgA 对 SARS-CoV-2 变体的交叉结合能力明显更高（均 p<0.0001），这强调了在研究黏膜免疫反应时考虑潜在血清来源的单体 IgA 的重要性。
总之，尽管可以在鼻分泌物和唾液中可靠地测量刺突特异性 IgA，但我们的研究结果表明，与唾液相比，鼻分泌物中的 IgA 水平更高，可能 SIgA 比例也更大。我们进一步证实了 SIgA 在黏膜分泌物中具有更高的变体交叉结合能力，突出了针对上呼吸道的疫苗的潜在保护益处。
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