Abstract
Background We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.
Methods Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively.
Results After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years (β=-0.94, p=0.001) and malignancy (β=-0.88, p=0.002) reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p=0.004); (β=-0.66, p=0.014)], diabetes mellitus [(β=-0.57, p=0.032); (β=-0.44, p=0.028)], and systemic steroid use [(β=-0.066, p=0.032); (β=-0.55, p=0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2, but the immune response decreased with malignancy (β =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001).
Conclusion Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Prior COVID-19 infection enhances the booster-dose response except in individuals with malignancy, suggesting a need for clinically guiding vaccine dosing regimens.
Summary Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination. All subjects, irrespective of prior COVID infection, benefited from a third dose. Malignancy decreased response following third dose, suggesting the importance of clinically guided vaccine regimens.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
Funding for this study was provided by the National Institutes of Health (awards R01 AI150334 to RES). The analysis was supported by Global Health Equity Scholars (FIC D43TW010540 to RS), the NIH (5T32AI007517-20 to LP) and the Yale School of Medicine Medical Student Research Fellowship (AHS).
Author Declarations
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The study was approved by the Institutional Review Board at the Veteran's Affairs (VA) Connecticut Healthcare System. Written informed consent was obtained from each participant.
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Footnotes
The updated manuscript reflects addition of new data of durability of vaccination response after third dose. Tables 1 and S1, Figures 1 and 4 updated. Figure S1 removed, S2 is now S1.
Data Availability
All data produced in the present work are contained in the manuscript.