Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population

BackgroundWe studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population. MethodsSera (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. ResultsAfter 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-naive individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years ({beta}=-0.94, p=0.001) and malignancy ({beta}=-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 [({beta}=-1.10, p=0.004); ({beta}=-0.66, p=0.014)], diabetes mellitus [({beta}=-0.57, p=0.032); ({beta}=-0.44, p=0.028)], and systemic steroid use [({beta}=-0.066, p=0.032); ({beta}=-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 ({beta} =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001). ConclusionMultiple 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. SummaryMultiple 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.