Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan

Abstract

: Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age <40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19–2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19–3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets.

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“…On the other hand, higher lymphocyte counts in people who consumed alcohol have been found [ 88 ]. Smoking was not associated with T cell responses, in line with Tani and co-authors [ 31 ]. However, Costa and co-authors [ 36 ] found that current smoking increased T cell responses.…”

“…In our cohort, the percentage of CD4+ and CD8+ T cell responders was higher than that observed in other studies at the population level or in healthcare workers in cross-sectional [ 30 , 31 ] or cohort studies [ 13 , 32 , 33 , 34 , 35 , 36 , 37 ]. However, several tests to measure immune response were used with diverse SARS-CoV-2 variants and the follow-up was variable, but reached a minimum of six months.…”

“…Alcohol consumption was associated with the CD8+ T cell response. In contrast, Tani and co-authors [ 31 ] had not found this association in a cohort of mRNA vaccinated individuals. On the other hand, higher lymphocyte counts in people who consumed alcohol have been found [ 88 ].…”

“…In addition, Gil-Manso and co-authors [ 86 ] found that blood group O presented significantly lower frequencies of specific CD4+ T cell responses compared with non-O blood groups. However, no associations between blood groups and cellular immune responses have been reported in other studies [ 31 ].…”

“…In Italy, Sabetta and co-authors conducted a cohort study [ 85 ] and did not find an association of cellular immune response with age or sex. In Japan, Tani and co-authors [ 31 ] detected, after a booster mRNA vaccine, an increase in T cell response in participants aged ≤40 years and those with adverse reactions to the second or third vaccine dose.…”