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Link to original content: https://pubmed.ncbi.nlm.nih.gov/35857583
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. 2022 Oct 28;7(76):eadd4853.
doi: 10.1126/sciimmunol.add4853. Epub 2022 Oct 21.

Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

Jinyi Tang  1   2   3 , Cong Zeng  4   5 , Thomas M Cox  3 , Chaofan Li  1   2   3 , Young Min Son  1   6 , In Su Cheon  1   2   3 , Yue Wu  7 , Supriya Behl  8 , Justin J Taylor  9 , Rana Chakaraborty  8 , Aaron J Johnson  7 , Dante N Shiavo  3 , James P Utz  3 , Janani S Reisenauer  3 , David E Midthun  3 , John J Mullon  3 , Eric S Edell  3 , Mohamad G Alameh  10 , Larry Borish  11 , William G Teague  12 , Mark H Kaplan  13 , Drew Weissman  10 , Ryan Kern  3 , Haitao Hu  14 , Robert Vassallo  3 , Shan-Lu Liu  4   5 , Jie Sun  1   2   3   7
Affiliations

Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

Jinyi Tang et al. Sci Immunol. .

Abstract

SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S-specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19-vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.

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Figures

Fig. 1.
Fig. 1.
Systemic and respiratory antibody responses in COVID-19 convalescents and vaccinated individuals. (A) Schematic of recruited cohorts (n=5 for unvaccinated donor, n=19 for vaccinated, and n=10 for COVID-19 hospitalized convalescent) and experimental procedures. Figures were created with BioRender. (B to E), Levels of SARS-CoV-2 S1 or RBD binding IgG (B and C) or IgA (D and E) in plasma and bronchoalveolar (BAL) fluid of unvaccinated donors (n=5), COVID-19 vaccinated (n=17) or convalescents (n=9). One receiving J&J was indicated as pink in the vaccinated group. Three individuals receiving the booster (BNT162b2 or mRNA-1273) were indicated as orange in the vaccinated group. Enrolled donors’ demographics were provided in Table. S1 or previous publication ( 19 ). Data in (B to E) are means ± SEM. Statistical differences were determined by one-way ANOVA and p values were indicated by ns, not significant (P > 0.05), * (p < 0.05), ** (p < 0.01), *** (p < 0.001), and **** (p < 0.0001).
Fig. 2.
Fig. 2.. COVID-19-vaccinated individuals exhibit lower respiratory neutralizing antibody responses compared to convalescents.
Plasma and BAL neutralizing activity in unvaccinated donors, vaccinated and convalescent individuals. (A to C) Neutralizing antibody titers (NT50) in plasma against SARS-CoV-2 S D614G (A) Delta (B) and Omicron BA.1.1 (C) pseudotyped virus in unvaccinated donors (n=5), vaccinated (n=17) and convalescent (n=10) individuals. HEK293T-ACE2 cells were used as targeted cells for infection. (D to F) Neutralizing antibody titers (NT50) in BAL against SARS-CoV-2 S D614G (D), Delta (E) and Omicron BA.1.1 (F) pseudotyped virus in unvaccinated donor (n=5), vaccinated (n=17) and convalescent individuals (n=10). One receiving J&J was indicated as pink in the vaccinated group. Three individuals receiving the booster shot (BNT162b2 or mRNA-1273) were indicated as orange in the vaccinated group. nAb, neutralizing antibody. LOD, limit of detection. Data are means ± SEM. Statistical differences were determined by one-way ANOVA and p values were indicated by ns, not significant (P > 0.05), * (p < 0.05), ** (p < 0.01), *** (p < 0.001), and **** (p < 0.0001).
Fig. 3.
Fig. 3.
COVID-19-vaccinated individuals exhibit systemic cellular immunity not evident in the respiratory tract. (A) Frequency of SARS-CoV-2 RBD- specific B cells in the blood (PBMC) and the BAL of vaccinated (n=14). (B and C) Frequencies of TNF- and IFN-γ- producing CD8+ (B) or CD4+ (C) T cells in the blood (PBMC) and the BAL of vaccinated (n=13) after S peptide pools stimulation. (D) Frequency of SARS-CoV-2 RBD- specific B cells in the blood (PBMC) and the BAL of convalescent individuals (n=8). (E and F) Frequencies of TNF- and IFN-γ- producing CD8+ (E) or CD4+ (F) T cells in the blood (PBMC) and the BAL of convalescents (n=5) after S peptide pools stimulation. Data are means ± SEM. Numbers below the graph show ratio of positive staining within total samples. Statistical differences were determined by paired t test in A to D and independent t test in E and F. P values were indicated by ns, not significant (P > 0.05), * (p < 0.05), ** (p < 0.01), and *** (p < 0.001).
Fig. 4.
Fig. 4.
Combination of mRNA plus mucosal adenovirus immunization induces high levels of mucosal neutralizing activity against SARS-CoV-2 Omicron BA.1.1. C57BL/6 mice were immunized as indicated. (A) Schematic of vaccination strategy and experimental parameters; n=10 for PBS control (mock), n=7 for two doses of mRNA (mRNA*2 (i.m.)), n=7 for three doses of mRNA (mRNA*3 (i.m.)), n=8 for two doses of mRNA plus S-trimer with cGAMP immunization (mRNA*2 (i.m.)+ S-trimer with cGAMP (i.n.), and n=8 for two doses of mRNA plus Ad5-S immunization (mRNA*2 (i.m.)+ Ad5-S (i.n.)). (B) Cell numbers of RBD+ B in the BAL following immunization. (C) Cell numbers of TNF- and IFN-γ- producing CD8+ or CD4+ T in the BAL following immunization. (D and E) Levels of S1- and RBD- specific IgG (D) or IgA (E) were measured from BAL. (F to H) NT50 of BAL against SARS-CoV-2 S D614G (F), Delta (G) and Omicron BA.1.1 (H) pseudotyped virus were measured. i.m., intramuscular. i.n., intranasal. nAb, neutralizing antibody. LOD, limit of detection. Data are pooled from two independent experiments. Data in (B to H) are means ± SEM. Statistical differences were determined by one-way ANOVA and p values were indicated by * (p < 0.05), ** (p < 0.01), *** (p < 0.001) and **** (p < 0.0001).
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References

    1. Krammer F., SARS-CoV-2 vaccines in development. Nature 586, 516–527 (2020). 10.1038/s41586-020-2798-3 - DOI - PubMed
    1. Carvalho T., Krammer F., Iwasaki A., The first 12 months of COVID-19: A timeline of immunological insights. Nat. Rev. Immunol. 21, 245–256 (2021). 10.1038/s41577-021-00522-1 - DOI - PMC - PubMed
    1. Sadarangani M., Marchant A., Kollmann T. R., Immunological mechanisms of vaccine-induced protection against COVID-19 in humans. Nat. Rev. Immunol. 21, 475–484 (2021). 10.1038/s41577-021-00578-z - DOI - PMC - PubMed
    1. Gupta R. K., Topol E. J., COVID-19 vaccine breakthrough infections. Science 374, 1561–1562 (2021). 10.1126/science.abl8487 - DOI - PubMed
    1. Siddle K. J., Krasilnikova L. A., Moreno G. K., Schaffner S. F., Vostok J., Fitzgerald N. A., Lemieux J. E., Barkas N., Loreth C., Specht I., Tomkins-Tinch C. H., Paull J. S., Schaeffer B., Taylor B. P., Loftness B., Johnson H., Schubert P. L., Shephard H. M., Doucette M., Fink T., Lang A. S., Baez S., Beauchamp J., Hennigan S., Buzby E., Ash S., Brown J., Clancy S., Cofsky S., Gagne L., Hall J., Harrington R., Gionet G. L., DeRuff K. C., Vodzak M. E., Adams G. C., Dobbins S. T., Slack S. D., Reilly S. K., Anderson L. M., Cipicchio M. C., DeFelice M. T., Grimsby J. L., Anderson S. E., Blumenstiel B. S., Meldrim J. C., Rooke H. M., Vicente G., Smith N. L., Messer K. S., Reagan F. L., Mandese Z. M., Lee M. D., Ray M. C., Fisher M. E., Ulcena M. A., Nolet C. M., English S. E., Larkin K. L., Vernest K., Chaluvadi S., Arvidson D., Melchiono M., Covell T., Harik V., Brock-Fisher T., Dunn M., Kearns A., Hanage W. P., Bernard C., Philippakis A., Lennon N. J., Gabriel S. B., Gallagher G. R., Smole S., Madoff L. C., Brown C. M., Park D. J., MacInnis B. L., Sabeti P. C., Transmission from vaccinated individuals in a large SARS-CoV-2 Delta variant outbreak. Cell 185, 485–492.e10 (2022). 10.1016/j.cell.2021.12.027 - DOI - PMC - PubMed

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