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. 2021 Oct 12:12:744887.
doi: 10.3389/fimmu.2021.744887. eCollection 2021.

The Mucosal and Serological Immune Responses to the Novel Coronavirus (SARS-CoV-2) Vaccines

Renee W Y Chan  1   2   3   4 , Shaojun Liu  1   2   3   4 , Jonathan Y Cheung  1   2   3   4 , Joseph G S Tsun  1   2   3   4 , Kate C Chan  1   2 , Kathy Y Y Chan  1   2 , Genevieve P G Fung  1 , Albert M Li  1   2   4 , Hugh Simon Lam  1   2
Affiliations

The Mucosal and Serological Immune Responses to the Novel Coronavirus (SARS-CoV-2) Vaccines

Renee W Y Chan et al. Front Immunol. .

Abstract

Background: Although the serological antibody responses induced by SARS-CoV-2 vaccines are well characterized, little is known about their ability to elicit mucosal immunity.

Objectives: This study aims to examine and compare the mucosal and systemic responses of recipients of two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac).

Methods: Serial blood and nasal epithelial lining fluid (NELF) samples were collected from the recipients of either Comirnaty or CoronaVac. The plasma and NELF immunoglobulins A and G (IgA and IgG) specific to SARS-CoV-2 S1 protein (S1) and their neutralization effects were quantified.

Results: Comirnaty induced nasal S1-specific immunoglobulin responses, which were evident as early as 14 ± 2 days after the first dose. In 64% of the subjects, the neutralizing effects of NELF persisted for at least 50 days. Moreover, 85% of Comirnaty recipients exhibited S1-specific IgA and IgG responses in plasma by 14 ± 2 days after the first dose. By 7 ± 2 days after the booster, all plasma samples possessed S1-specific IgA and IgG responses and were neutralizing. The induction of S1-specific plasma antibodies by CoronaVac was IgG dominant, and 83% of the subjects possessed S1-specific IgG by 7 ± 2 days after the booster, with neutralizing effects.

Conclusion: Comirnaty induces S1-specific IgA and IgG responses with neutralizing activity in the nasal mucosa; a similar response is not seen with CoronaVac.

Clinical implication: The presence of a nasal response with mRNA vaccine may provide additional protection compared with inactivated virus vaccine. However, whether such widespread immunological response may produce inadvertent adverse effects in other tissues warrants further investigation.

Keywords: SARS-CoV-2; immunoglobulin A; immunoglobulin G; inactivated virus vaccine; mRNA vaccine; mucosal immunity; nasal epithelial lining fluid; serological immunity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Study design and demographics. There were three standard sampling time points and one extended sampling time point (fourth sampling) of biological sample collection: (i) 0 to 2 days before the first vaccination (baseline), (ii) 14 ± 2 days after the first vaccination (V+D14), (iii) 7 ± 2 days after the booster (B+D7), and (iv) any day between 14 days after the booster and before 3 months after the first vaccination. (B) Subjects vaccinated with CoronaVac (n = 18, pink table) and Comirnaty (n = 65, gray table) were recruited and followed longitudinally. There was a significant difference in their age distributions (p = 0.0061, Mann–Whitney test, two-tailed), and so 15 extra subjects vaccinated with CoronaVac were recruited to enrich the data for the fourth time point.
Figure 2
Figure 2
Expression of nasal epithelial lining fluid (NELF) and plasma S1-specific IgA and IgG and neutralizing antibody (NAb). The level of S1-specific IgA (green dots) and IgG (red dots) were plotted against the three standard time points of sample collection in NELF (A, D) and plasma (B, E) specimens of the recipients of CoronaVac (A, B) and Comirnaty (D, E). The data points above the dotted line (sample/calibrator ratio ≥1.1) are considered positive, while the dotted lines at y = 15 indicate the upper detection limit of the assay. The asterisks indicate statistical significance between time points of the same Ig class by Friedman test, followed by Dunn’s multiple-comparison test. **p < 0.001, ***p < 0.0005, and ****p < 0.0001. The percentage of signal inhibition observed with the surrogate SARS-Co-V 2 neutralization antibody detection kit by the NELF and plasma samples of CoronaVac (C) and Comirnaty (F) recipients collected on 7 ± 2 days after the booster is plotted. The 30% signal inhibition cutoff for SARS-CoV-2 NAb detection is interpreted as the sample containing neutralizing antibodies for SARS-CoV-2.
Figure 3
Figure 3
Correlation between S1-specific Igs to the age of the vaccinated subjects. The SARS-CoV-2 S1-specific antibody levels in the nasal epithelial lining fluid (NELF) (A, B, E, F) and plasma (C, D, G, H) samples detected at baseline, 14 ± 2 days after the first dose (V+14), and 7 ± 2 days after the booster (B+7) time points are plotted against the age of the vaccine recipients. Significant correlations are denoted with the Spearman r and the p-value. Pink and green dotted lines represent significant linear regression fits with 95% confidence intervals (shaded region with the corresponding colors). Sample/calibrator ≥1.1 is regarded as the threshold of a positive sample, indicated by the horizontal dotted line.
Figure 4
Figure 4
Correlation of S1-specific Igs to the percentage of signal inhibition in the surrogate ACE-2-based neutralization readout. The correlation coefficients of the levels of the (A) plasma of CoronaVac subjects, (B) nasal epithelial lining fluid (NELF), and (C) plasma of Comirnaty subjects at 7 ± 2 days after the booster with the NAb are superimposed on the panel with the trend lines estimated with the use of simple linear regression. The plots show the S/C ratio of the SARS-CoV-2 S1-specific IgA (green dots) and IgG (orange dots) <15 plotted against the percentage of inhibition of the SARS-CoV-2 spike-ACE-2 binding signal, in which inhibition ≥30% is regarded as the threshold of a positive sample, indicated by the vertical dotted line. Out-range specific antibody levels were excluded from the two-tailed Spearman correlation analysis. The green and orange dotted lines represent significant linear regression fits with 95% confidence intervals (shaded region with the corresponding colors).
Figure 5
Figure 5
Longevity of the NAb in nasal epithelial lining fluid (NELF) and plasma samples. The paired percentage of signal inhibition in the (A) NELF and (B) plasma of 24 Comirnaty subjects and (C) plasma of CoronaVac recipients in the longitudinal group (n = 12, red dots) and in the cross-sectional group (n = 15) are shown. The data points of the same individual are joined by a dotted line.
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References

    1. Organization WH . WHO Coronavirus (COVID-19) Dashboard. (2021). WHO Press - World Health Organization.
    1. International Nonproprietary Names Programme . Messenger RNA Encoding the Full-Length SARS-CoV-2 Spike Glycoprotein. World Health Organization; (2020). WHO Press - World Health Organization.
    1. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med (2020) 383(27):2603–15. doi: 10.1056/NEJMoa2034577 - DOI - PMC - PubMed
    1. Wu Z, Hu Y, Xu M, Chen Z, Yang W, Jiang Z, et al. . Safety, Tolerability, and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Adults Aged 60 Years and Older: A Randomised, Double-Blind, Placebo-Controlled, Phase 1/2 Clinical Trial. Lancet Infect Dis (2021) 21(6):803–12. doi: 10.1016/S1473-3099(20)30987-7 - DOI - PMC - PubMed
    1. Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, et al. . Safety, Tolerability, and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine in Healthy Adults Aged 18-59 Years: A Randomised, Double-Blind, Placebo-Controlled, Phase 1/2 Clinical Trial. Lancet Infect Dis (2021) 21(2):181–92. doi: 10.1016/S1473-3099(20)30843-4 - DOI - PMC - PubMed

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