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Differential Dynamics of Humoral and Cell-Mediated Immunity with Three Doses of BNT162b2 SARS-CoV-2 Vaccine in Healthcare Workers in Japan: A Prospective Cohort Study

ABSTRACT: Vaccines against SARS-CoV-2 with good efficacy are now available worldwide. However, gained immunity diminishes over time. Here, we investigate the course of both humoral and cell-mediated immunity in response to three doses of the Pfizer mRNA BNT162b2 SARS-CoV-2 vaccine in healthcare workers in Japan. SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies (total Ig, IgG), neutralizing antibodies (NAb), and ELISpot were measured in serum and whole blood samples collected after each vaccine dose. ELISpot numbers were higher than the cutoff values in most participants at all times. It was suggested that the difference in behavior between humoral immunity and cell-mediated immunity with age is complementary. Anti-RBD total Ig, IgG, and NAb indicated a high correlation at each time point after vaccine doses. Total Ig was retained long-term after the second dose and increased significantly faster by the booster dose than IgG. Nab levels of all subjects were ≤20% six months after the second dose, and the correlation coefficient was greatly reduced. These are due to the avidity of each antibody and differences among commercial kits, which may affect the evaluation of immunokinetics in previous COVID-19 studies. Therefore, it is necessary to harmonize reagents categorized by the same characteristics.

SUBMITTER: Yamashita K

PROVIDER: S-EPMC9323262 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe inactivated virus vaccine, BBIBP-CorV, was principally distributed across low- and middle-income countries as primary vaccination strategy to prevent poor COVID-19 outcomes. Limited information is available regarding its effect on heterologous boosting. We aim to evaluate the immunogenicity and reactogenicity of a third booster dose of BNT162b2 following a double BBIBP-CorV regime.MethodsWe conducted a cross-sectional study among healthcare providers from several healthcare facilities of the Seguro Social de Salud del Perú - ESSALUD. We included participants two-dose BBIBP-CorV vaccinated who presented a three-dose vaccination card at least 21 days passed since the vaccinees received their third dose and were willing to provide written informed consent. Antibodies were determined using LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin Inc., Stillwater, USA). Factors potentially associated with immunogenicity, and adverse events, were considered. We used a multivariable fractional polynomial modeling approach to estimate the association between anti-SARS-CoV-2 IgG antibodies' geometric mean (GM) ratios and related predictors.ResultsWe included 595 subjects receiving a third dose with a median (IQR) age of 46 [37], [54], from which 40% reported previous SARS-CoV-2 infection. The overall geometric mean (IQR) of anti-SARS-CoV-2 IgG antibodies was 8,410 (5,115 - 13,000) BAU/mL. Prior SARS-CoV-2 history and full/part-time in-person working modality were significantly associated with greater GM. Conversely, time from boosting to IgG measure was associated with lower GM levels. We found 81% of reactogenicity in the study population; younger age and being a nurse were associated with a lower incidence of adverse events.ConclusionsAmong healthcare providers, a booster dose of BNT162b2 following a full BBIBP-CorV regime provided high humoral immune protection. Thus, SARS-CoV-2 previous exposure and working in person displayed as determinants that increase anti-SARS-CoV-2 IgG antibodies.

Dataset Information

Differential Dynamics of Humoral and Cell-Mediated Immunity with Three Doses of BNT162b2 SARS-CoV-2 Vaccine in Healthcare Workers in Japan: A Prospective Cohort Study

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