Frontiers in Immunology (Aug 2023)
Natural killer cells and BNT162b2 mRNA vaccine reactogenicity and durability
- Elizabeth K. Graydon,
- Elizabeth K. Graydon,
- Tonia L. Conner,
- Kim Dunham,
- Cara Olsen,
- Emilie Goguet,
- Emilie Goguet,
- Si’Ana A. Coggins,
- Si’Ana A. Coggins,
- Marana Rekedal,
- Marana Rekedal,
- Emily Samuels,
- Emily Samuels,
- Belinda Jackson-Thompson,
- Belinda Jackson-Thompson,
- Matthew Moser,
- Matthew Moser,
- Alyssa Lindrose,
- Alyssa Lindrose,
- Monique Hollis-Perry,
- Gregory Wang,
- Gregory Wang,
- Santina Maiolatesi,
- Santina Maiolatesi,
- Yolanda Alcorta,
- Yolanda Alcorta,
- Anatalio Reyes,
- Anatalio Reyes,
- Mimi Wong,
- Mimi Wong,
- Kathy Ramsey,
- Kathy Ramsey,
- Julian Davies,
- Julian Davies,
- Edward Parmelee,
- Edward Parmelee,
- Orlando Ortega,
- Orlando Ortega,
- Mimi Sanchez,
- Mimi Sanchez,
- Sydney Moller,
- Jon Inglefield,
- David Tribble,
- Timothy Burgess,
- Robert O’Connell,
- Allison M. W. Malloy,
- Simon Pollett,
- Simon Pollett,
- Christopher C. Broder,
- Eric D. Laing,
- Stephen K. Anderson,
- Edward Mitre
Affiliations
- Elizabeth K. Graydon
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Elizabeth K. Graydon
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Tonia L. Conner
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Kim Dunham
- Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Cara Olsen
- Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Emilie Goguet
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Emilie Goguet
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Si’Ana A. Coggins
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Si’Ana A. Coggins
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Marana Rekedal
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Marana Rekedal
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Emily Samuels
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Emily Samuels
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Belinda Jackson-Thompson
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Belinda Jackson-Thompson
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Matthew Moser
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Matthew Moser
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Alyssa Lindrose
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Alyssa Lindrose
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Monique Hollis-Perry
- Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center (NMRC), Silver Spring, MD, United States
- Gregory Wang
- Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center (NMRC), Silver Spring, MD, United States
- Gregory Wang
- General Dynamics Information Technology, Silver Spring, MD, United States
- Santina Maiolatesi
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Santina Maiolatesi
- Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center (NMRC), Silver Spring, MD, United States
- Yolanda Alcorta
- Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center (NMRC), Silver Spring, MD, United States
- Yolanda Alcorta
- General Dynamics Information Technology, Silver Spring, MD, United States
- Anatalio Reyes
- Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center (NMRC), Silver Spring, MD, United States
- Anatalio Reyes
- General Dynamics Information Technology, Silver Spring, MD, United States
- Mimi Wong
- Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center (NMRC), Silver Spring, MD, United States
- Mimi Wong
- General Dynamics Information Technology, Silver Spring, MD, United States
- Kathy Ramsey
- Clinical Trials Center, Infectious Diseases Directorate, Naval Medical Research Center (NMRC), Silver Spring, MD, United States
- Kathy Ramsey
- General Dynamics Information Technology, Silver Spring, MD, United States
- Julian Davies
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Julian Davies
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Edward Parmelee
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Edward Parmelee
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Orlando Ortega
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Orlando Ortega
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Mimi Sanchez
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Mimi Sanchez
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Sydney Moller
- Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Jon Inglefield
- Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- David Tribble
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Timothy Burgess
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Robert O’Connell
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Allison M. W. Malloy
- Department of Pediatrics, Uniformed Services University, Bethesda, MD, United States
- Simon Pollett
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States
- Simon Pollett
- Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University, Bethesda, MD, United States
- Christopher C. Broder
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Eric D. Laing
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- Stephen K. Anderson
- Frederick National Laboratory for Cancer Research, Frederick, MD, United States
- Edward Mitre
- Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, United States
- DOI
- https://doi.org/10.3389/fimmu.2023.1225025
- Journal volume & issue
-
Vol. 14
Abstract
IntroductionNatural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2).MethodsWe analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1st and 2nd doses of BNT162b2. Inflammatory side effects were assessed by structured symptom questionnaires, and baseline NK cell functionality was quantified by an in vitro killing assay on participants that reported high or low post-vaccination symptom scores.ResultsKey observations include: 1) circulating NK cells exhibit evidence of activation in the week following vaccination, 2) individuals with high symptom scores after 1st vaccination had higher pre-vaccination NK cytotoxicity indices, 3) high pre-vaccination NK cell numbers were associated with lower spike-specific IgG levels six months after two BNT162b2 doses, and 4) expression of the inhibitory marker NKG2A on immature NK cells was associated with higher antibody responses 1 and 6 months post-vaccination.DiscussionThese results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.
Keywords
