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. 2023 Dec:98:104893.
doi: 10.1016/j.ebiom.2023.104893. Epub 2023 Nov 29.

SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses

Olha Puhach  1 , Mathilde Bellon  1 , Kenneth Adea  1 , Meriem Bekliz  1 , Krisztina Hosszu-Fellous  2 , Pascale Sattonnet  1 , Nicolas Hulo  3 , Laurent Kaiser  2 , Isabella Eckerle  4 , Benjamin Meyer  5
Affiliations

SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses

Olha Puhach et al. EBioMedicine. 2023 Dec.

Abstract

Background: Mucosal antibodies play a key role in the protection against SARS-CoV-2 infection in the upper respiratory tract, and potentially in limiting virus replication and therefore onward transmission. While systemic immunity to SARS-CoV-2 is well understood, we have a limited understanding about the antibodies present on the nasal mucosal surfaces.

Methods: In this study, we evaluated SARS-CoV-2 mucosal antibodies following previous infection, vaccination, or a combination of both. Paired nasal fluid and serum samples were collected from 143 individuals, which include convalescent, vaccinated, or breakthrough infections.

Findings: We detected a high correlation between IgG responses in serum and nasal fluids, which were higher in both compartments in vaccinated compared to convalescent participants. Contrary, nasal and systemic SARS-CoV-2 IgA responses were weakly correlated, indicating a compartmentalization between the local and systemic IgA responses. SARS-CoV-2 secretory component IgA (s-IgA) antibodies, present exclusively on mucosal surfaces, were detected in the nasal fluid only in a minority of vaccinated subjects and were significantly higher in previously infected individuals. Depletion of IgA antibodies in nasal fluids resulted in a tremendous reduction of neutralization activity against SARS-CoV-2, indicating that IgA is the crucial contributor to neutralization in the nasal mucosa. Neutralization against SARS-CoV-2 was higher in the mucosa of subjects with previous SARS-CoV-2 infections compared to vaccinated participants.

Interpretation: In summary, we demonstrate that currently available vaccines elicit strong systemic antibody responses, but SARS-CoV-2 infection generates higher titers of binding and neutralizing mucosal antibodies. Our results support the importance to develop SARS-CoV-2 vaccines that elicit mucosal antibodies.

Funding: The work was funded by the COVID-19 National Research Program 78 (grant number 198412) of the Swiss National Science Foundation.

Keywords: COVID-19; Mucosal immunity; SARS-CoV-2; Secretory IgA.

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Conflict of interest statement

Declaration of interests BM declares grants from Moderna, outside the scope of the submitted work. IE declares grants and speakers fees from Moderna, outside the scope of the submitted work. The remaining authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Correlation of SARS-CoV-2 IgA and IgG antibody responses in NLF and serum. Correlation between anti-triS serum and NLF IgA (a) and IgG (b) antibody titers (log10 ng/mL) of samples collected from convalescent, vaccinated and subjects with hybrid immunity. NLF triS IgA titers normalized to the levels of total IgA from the same sample. Spearman rank correlation coefficient and p values are shown.
Fig. 2
Fig. 2
Mucosal and serum antibody responses in subjects with previous infection compared to vaccinated only. (a and b) Anti-triS IgA (log10 ng/mL) measured in NLF (a) and serum (b) of vaccinated with 2 or 3 doses, or convalescent. (c) Anti-triS s-IgA (log10 AU/mL) antibody titers in NLF of vaccinated with 2 or 3 doses, or convalescent. (d and e) Anti-triS IgG (log10 ng/mL) measured in NLF (d) and serum (e) of vaccinated with 2 or 3 doses, or convalescent. A generalized linear model was used to determine differences of means, p values are shown above brackets. The mean + 3SD of 11 negative samples was used to set a cut-off for anti-triS IgA, s-IgA and IgG in NLF. The mean + 3SD of 56 pre-pandemic serum samples was used to set a cut-off for anti-triS IgA in serum samples. The mean + 3SD of 48 pre-pandemic serum samples was used to set a cut-off for anti-triS IgG in serum samples.
Fig. 3
Fig. 3
Mucosal and serum antibody responses in convalescent compared to subjects with hybrid immunity. (a and b) Anti-triS IgA (log10 ng/mL) measured in NLF (a) and serum (b) of convalescent or subjects with hybrid immunity. (c) Anti-triS s-IgA (log10 AU/mL) antibody titers in NLF of convalescent or subjects with hybrid immunity. (d and e) Anti-triS IgG measured in NLF (d) and serum (e) of convalescent or subjects with hybrid immunity. A generalized linear model was used to determine differences of means, p values are shown above brackets. The mean + 3SD of 11 negative samples was used to set a cut-off for anti-triS IgA, s-IgA and IgG in NLF. The mean + 3SD of 56 pre-pandemic serum samples was used to set a cut-off for anti-triS IgA in serum samples. The mean + 3SD of 48 pre-pandemic serum samples was used to set a cut-off for anti-triS IgG in serum samples.
Fig. 4
Fig. 4
Neutralizing antibody responses in the nasal mucosae of vaccinated and subjects with hybrid immunity. (a) Each dot represents the neutralizing titer (FRNT50) of an individual NLF sample against SARS-CoV-2 ancestral (a) and Omicron BA.5 variant (b). (c) IgA antibodies were purified from the NLFs, each symbol represents the same subject. Neutralizing titers against ancestral SARS-CoV-2 measured from different fractions are displayed. The generalized linear model was used to determine differences of means, p values are shown above brackets.
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