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Systems vaccinology of the BNT162b2 mRNA vaccine in humans.
Arunachalam, Prabhu S; Scott, Madeleine K D; Hagan, Thomas; Li, Chunfeng; Feng, Yupeng; Wimmers, Florian; Grigoryan, Lilit; Trisal, Meera; Edara, Venkata Viswanadh; Lai, Lilin; Chang, Sarah Esther; Feng, Allan; Dhingra, Shaurya; Shah, Mihir; Lee, Alexandra S; Chinthrajah, Sharon; Sindher, Sayantani B; Mallajosyula, Vamsee; Gao, Fei; Sigal, Natalia; Kowli, Sangeeta; Gupta, Sheena; Pellegrini, Kathryn; Tharp, Gregory; Maysel-Auslender, Sofia; Hamilton, Sydney; Aoued, Hadj; Hrusovsky, Kevin; Roskey, Mark; Bosinger, Steven E; Maecker, Holden T; Boyd, Scott D; Davis, Mark M; Utz, Paul J; Suthar, Mehul S; Khatri, Purvesh; Nadeau, Kari C; Pulendran, Bali.
  • Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Scott MKD; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Hagan T; Center for Biomedical Informatics, Department of Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Li C; Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Feng Y; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Wimmers F; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Grigoryan L; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Trisal M; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Edara VV; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Lai L; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Chang SE; Yerkes National Primate Research Center, Atlanta, GA, USA.
  • Feng A; Yerkes National Primate Research Center, Atlanta, GA, USA.
  • Dhingra S; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Shah M; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Lee AS; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Chinthrajah S; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Sindher SB; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Mallajosyula V; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Gao F; Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.
  • Sigal N; Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.
  • Kowli S; Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.
  • Gupta S; Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.
  • Pellegrini K; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Tharp G; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Maysel-Auslender S; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Hamilton S; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Aoued H; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Hrusovsky K; Yerkes National Primate Research Center, Atlanta, GA, USA.
  • Roskey M; Yerkes National Primate Research Center, Atlanta, GA, USA.
  • Bosinger SE; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Maecker HT; Yerkes National Primate Research Center, Atlanta, GA, USA.
  • Boyd SD; Yerkes National Primate Research Center, Atlanta, GA, USA.
  • Davis MM; Quanterix, Billerica, MA, USA.
  • Utz PJ; Quanterix, Billerica, MA, USA.
  • Suthar MS; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Khatri P; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
  • Nadeau KC; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Pulendran B; Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.
Nature ; 596(7872): 410-416, 2021 08.
Article in English | MEDLINE | ID: covidwho-1305364
ABSTRACT
The emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2). Vaccination resulted in the robust production of neutralizing antibodies against the wild-type SARS-CoV-2 (derived from 2019-nCOV/USA_WA1/2020) and, to a lesser extent, the B.1.351 strain, as well as significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a notably enhanced innate immune response as compared to primary vaccination, evidenced by (1) a greater frequency of CD14+CD16+ inflammatory monocytes; (2) a higher concentration of plasma IFNγ; and (3) a transcriptional signature of innate antiviral immunity. Consistent with these observations, our single-cell transcriptomics analysis demonstrated an approximately 100-fold increase in the frequency of a myeloid cell cluster enriched in interferon-response transcription factors and reduced in AP-1 transcription factors, after secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and neutralizing antibody responses, and show that a monocyte-related signature correlates with the neutralizing antibody response against the B.1.351 variant. Collectively, these data provide insights into the immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response after booster immunization.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes / Adaptive Immunity / Vaccinology / COVID-19 Vaccines / COVID-19 / Immunity, Innate / Antibodies, Viral Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Nature Year: 2021 Document Type: Article Affiliation country: S41586-021-03791-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes / Adaptive Immunity / Vaccinology / COVID-19 Vaccines / COVID-19 / Immunity, Innate / Antibodies, Viral Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Nature Year: 2021 Document Type: Article Affiliation country: S41586-021-03791-x