TY - JOUR
T1 - Natural killer cells and BNT162b2 mRNA vaccine reactogenicity and durability
AU - Graydon, Elizabeth K.
AU - Conner, Tonia L.
AU - Dunham, Kim
AU - Olsen, Cara
AU - Goguet, Emilie
AU - Coggins, Si’Ana A.
AU - Rekedal, Marana
AU - Samuels, Emily
AU - Jackson-Thompson, Belinda
AU - Moser, Matthew
AU - Lindrose, Alyssa
AU - Hollis-Perry, Monique
AU - Wang, Gregory
AU - Maiolatesi, Santina
AU - Alcorta, Yolanda
AU - Reyes, Anatalio
AU - Wong, Mimi
AU - Ramsey, Kathy
AU - Davies, Julian
AU - Parmelee, Edward
AU - Ortega, Orlando
AU - Sanchez, Mimi
AU - Moller, Sydney
AU - Inglefield, Jon
AU - Tribble, David
AU - Burgess, Timothy
AU - O’Connell, Robert
AU - Malloy, Allison M.W.
AU - Pollett, Simon
AU - Broder, Christopher C.
AU - Laing, Eric D.
AU - Anderson, Stephen K.
AU - Mitre, Edward
N1 - Publisher Copyright:
Copyright © 2023 Graydon, Conner, Dunham, Olsen, Goguet, Coggins, Rekedal, Samuels, Jackson-Thompson, Moser, Lindrose, Hollis-Perry, Wang, Maiolatesi, Alcorta, Reyes, Wong, Ramsey, Davies, Parmelee, Ortega, Sanchez, Moller, Inglefield, Tribble, Burgess, O’Connell, Malloy, Pollett, Broder, Laing, Anderson and Mitre.
PY - 2023
Y1 - 2023
N2 - Introduction: Natural 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). Methods: We 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. Results: Key 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. Discussion: These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.
AB - Introduction: Natural 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). Methods: We 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. Results: Key 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. Discussion: These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.
KW - COVID
KW - NK cells
KW - SARS-CoV-2 vaccine
KW - antibody durability
KW - mRNA vaccine
KW - reactogenicity
KW - vaccine side effects
UR - http://www.scopus.com/inward/record.url?scp=85170657231&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1225025
DO - 10.3389/fimmu.2023.1225025
M3 - Article
C2 - 37711632
AN - SCOPUS:85170657231
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1225025
ER -