Kinetics of humoral and cellular immune responses 5 months post-COVID-19 booster dose by immune response groups at the peak immunity phase: An observational historical cohort study using the Fukushima vaccination community survey

Abstract

Background: Understanding the waning of immunity after booster vaccinations is important to identify which immune-low populations should be prioritized.

Methods: We investigated longitudinal cellular and humoral immunity after the third vaccine dose in both high- and low-cellular and humoral immunity groups at the peak immunity phase after the booster vaccination in a large community-based cohort. Blood samples were collected from 1045 participants at peak (T1: median 54 days post-third dose) and decay (T2: median 145 days post-third dose) phases to assess IgG(S), neutralizing activity, and ELISpot responses. Participants were categorized into high/low ELISpot/IgG(S) groups at T1. Cellular and humoral responses were tracked for approximately five months after the third vaccination.

Results: In total, 983 participants were included in the cohort. IgG(S) geometric mean fold change between timepoints revealed greater waning in the >79 years age group (T2/T1 fold change: 0.27) and higher IgG(S) fold change in the low-ELISpot group at T1 (T2/T1 fold change: 0.32-0.33) than in the other groups, although ELISpot geometric mean remained stable.

Conclusions: Antibody level of those who did not respond well to third dose vaccination waned rapidly than those who responded well. Evidence-based vaccine strategies are essential in preventing potential health issues caused by vaccines, including side-effects.

Keywords: Booster dose vaccine effectiveness; COVID-19; Cellular immunity; Humoral immunity; SARS-CoV-2.

Fig. 1

Participant selection criteria. Participants were included in this study if they had received two doses of BNT162b and a third dose of BNT162b (Pfizer) or mRNA1273 (Moderna) and if they had their blood sampled during the peak phase (T1: median of day from third vaccine was 54 days) and decay phase (T2: median of day from third vaccine was 145 days). Participants who received their third doses between T1 and T2 or who were infected by T2 and who could not obtain the appropriate cellular immunology results were excluded.

Fig. 2

Immune level groups at T1 and age distribution. (A) Groups were designated based on the immunity at the peak phase (T1), the lower 25th quantile of ELISpot (<5, equally with not reactive in the official guidelines; n = 218), and IgG(S) (<1404.5; n = 245). Group 1 was defined as ELISpot high and IgG(S) high, Group 2 was ELISpot high and IgG(S) low, Group 3 was ELISpot low and IgG(S) high, and Group 4 was ELISpot low and IgG(S) low. IgG(S) antibody titers over 5000 are shown as 5000 in the figure and NAb over 800 are shown as 800 in the figure. (B) Age distribution in each cohort group (Groups 1–4).

Fig. 3

T-spot(S), Nab, and IgG(S) results at T2 (June 2022) by the immune level group at T1 (March 2022, Fig. 2). Results of the ELISpot at T2 (June 2022) in the immune 1–4 group at T1 (March 2022; see Fig. 2). The antibody titers at T2 indicated by the reactivity of ELISpot at T2 in immune Groups 1–4. Pattern of neutralizing antibodies (NAb), IgG (S), and T-spot at T2 phase among individuals who received a third dose booster. Individuals were divided into groups 1 to 4 based on the immune status of IgG(S) and T-spot at T1. Violin plots show the median level and interquartile range of NAb and IgG (S) according to non-reactive, borderline, and reactive immune status. The pie chart illustrates the proportion of the T-spot reactivity status at T2. IgG(S) antibody titers over 5000 are shown as 5000; NAb over 800 is shown as 800.