Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan

Abstract

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies.

Humoral response against spike protein enhanced by fifth and sixth COVID-19 mRNA vaccine in the uninfected and infected subjects

“…In Japan, it was reported that the fifth vaccination in dialysis patients resulted in 85% of the subjects obtaining 1000 AU/mL of IgG to spike protein, and a high antibody titer level was maintained. 17 It was also reported that the fifth immunization resulted in higher antibody titers in lung transplant patients than after the fourth vaccination. 18 The present study also showed that subjects with a history of infection had twice the antibody titers of non-infected subjects, consistent with previous reports.…”

SARS-CoV-2 Neutralization Capacity in Hemodialysis Patients with and without a Fifth Vaccination with the Updated Comirnaty Original/Omicron BA.4-5 Vaccine

“…Also, SARS-CoV-2 Wuhan strain-specific neutralizing and quantitative antibodies significantly increased after the fifth vaccination, showing that a fifth vaccination with the adapted bivalent vaccine stimulates an immune response targeting the original Wuhan strain virus and current VoCs in hemodialysis patients. A recent study by Tani et al that monitored hemodialysis patients’ COVID-19 vaccination response found large percentages of individuals with high Wuhan strain neutralizing and anti-spike (S) IgG antibodies already before the fifth vaccination to be increasing even further after the fifth vaccination with the adapted bivalent Comirnaty BA.4-5 vaccine [ 19 ]. Similar results were observed in a pseudovirus neutralization assay of the wild-type and Omicron BA.4-5 variants with a significantly increased cellular immunity after the bivalent vaccination (increased SARS-CoV-2 CD4+ and CD8+ T cell count and functionality against both wild-type and BA.4-5) [ 20 ].…”

“…In summary, immunocompromised patients are observed longitudinally regarding their serological and clinical response to SARS-CoV-2 immunization. The study is registered at Paul Ehrlich Institute (NIS592), and local ethics committee approval has been given as ethic vote 163/21 S-SR, on 19 March 2021, by the Medical Ethics Committee of the Klinikum rechts der Isar (Technical University of Munich). Patients were enrolled after providing written consent.…”

Diminished neutralizing activity against the XBB1.5 strain in 55.9% of individuals post 6 months COVID-19 mRNA booster vaccination: insights from a pseudovirus assay on 1,353 participants in the Fukushima vaccination community survey, Japan

“…The details are descried in our past paper ( 8 ). Briefly, SARS-CoV-2 specific spike protein IgG (IgG(S)) and nucleocapsid antibody IgG (IgG(N)) were measured.…”