2349. Natural Killer Cells and BNT162b2 mRNA Vaccine Reactogenicity and Durability
Authors: Graydon Elizabeth K , Conner Tonia , Dunham Kim , Olsen Cara , Goguet Emilie , Segard Allison , Coggins Si’Ana A , Tso Marana S , Samuels Emily C , Jackson-Thompson Belinda , Moser Matthew S , Lindrose Alyssa R , Hollis-Perry Monique , Wang Gregory , Maiolatesi Santina , Alcorta Yolanda , Reyes Anatalio , Wong Mimi , Ramsey Kathy , Davies Julian , Parmelee Edward , Ortega Orlando , Edwards Margaret Sanchez , Moller Sydney , Inglefield Jon , Tribble David , Burgess Timothy , O’Connell Robert , Malloy Allison M , Pollett Simon , Broder Christopher , Laing Eric D , Anderson Stephen , Mitre Edward 
Published: November 2023

Abstract

Background
Natural killer (NK) cells can both amplify and diminish 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 an increase in CD56dim CD16- NK cells compared to baseline levels, providing evidence of NK cell activation in the week following vaccination, 2) individuals with high symptom scores after 1st vaccination had higher pre-vaccination NK cytotoxicity indices compared to individuals with low symptoms scores (195.7 [SD 170.1] vs 118.5 [SD 77.5], p=0.04), and 3) pre-vaccination NK cell numbers were negatively correlated with spike-specific IgG levels six months after two BNT162b2 doses (Rho= -0.14, p=0.043).

Conclusion
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.

Disclosures
David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID response Timothy Burgess, MD, MPH, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial Simon Pollett, MBBS, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial