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Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination.
Tang, Jinyi; Zeng, Cong; Cox, Thomas M; Li, Chaofan; Son, Young Min; Cheon, In Su; Wu, Yue; Behl, Supriya; Taylor, Justin J; Chakaraborty, Rana; Johnson, Aaron J; Shiavo, Dante N; Utz, James P; Reisenauer, Janani S; Midthun, David E; Mullon, John J; Edell, Eric S; Alameh, Mohamad G; Borish, Larry; Teague, William G; Kaplan, Mark H; Weissman, Drew; Kern, Ryan; Hu, Haitao; Vassallo, Robert; Liu, Shan-Lu; Sun, Jie.
  • Tang J; Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
  • Zeng C; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • Cox TM; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Li C; Center for Retrovirus Research, Ohio State University, Columbus, OH 43210, USA.
  • Son YM; Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210, USA.
  • Cheon IS; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Wu Y; Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
  • Behl S; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • Taylor JJ; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Chakaraborty R; Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
  • Johnson AJ; Department of Systems Biotechnology, Chung-Ang University, Anseong, Gyeonggi-do 17546, Republic of Korea.
  • Shiavo DN; Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
  • Utz JP; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
  • Reisenauer JS; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Midthun DE; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
  • Mullon JJ; Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Edell ES; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Alameh MG; Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Borish L; Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
  • Teague WG; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Kaplan MH; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Weissman D; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Kern R; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Hu H; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Vassallo R; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Liu SL; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Sun J; Division of Asthma, Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Sci Immunol ; 7(76): eadd4853, 2022 10 28.
Article in English | MEDLINE | ID: covidwho-2088390
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Sci Immunol Year: 2022 Document Type: Article Affiliation country: Sciimmunol.add4853

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Sci Immunol Year: 2022 Document Type: Article Affiliation country: Sciimmunol.add4853