Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses

Abstract

BackgroundSARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity.ObjectiveTo determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection.Methods12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve.ResultsPeak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections.ConclusionBooster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.

Evaluation of T cell responses with the QuantiFERON SARS-CoV-2 assay in individuals with 3 doses of BNT162b2 vaccine, SARS-CoV-2 infection, or hybrid immunity

“…Limited data on the long-term duration of cell-mediated immunity have been reported after the third dose of the BNT162b2 mRNA vaccine [18] . Furthermore, the performance of IGRA in unvaccinated children and adults with SARS-CoV-2 infection is still under investigation, especially with the advent of new SARS-CoV-2 variants.…”

Early CD4+ T cell responses induced by the BNT162b2 SARS-CoV-2 mRNA vaccine predict immunological memory

“…The spike-specific T cells waned over time, and 6 months later, while spike-reactive CD4 + T cells were present in most individuals, spike-reactive CD8 + T cells were observed among only half of the individuals. Some studies have shown that the 3rd dose of SARS-CoV-2 mRNA vaccine induced higher T cell responses 43,44 , but other studies have demonstrated that T cell responsiveness was unchanged by the 3rd dose [45][46][47][48] . In contrast to the effect on antibody responses, the 3rd dose did not increase T cell epitopes and did not enhance T cell responses against the omicron variant [49][50][51] .…”

Immunity against Delta and Omicron variants elicited by homologous inactivated vaccine booster in kidney transplant recipients

“…Of note, Delta and Omicron variant spike-specific T cell frequency was significantly lower than Ancestral strain spike-specific T cell frequency in HVs and KTRs. The diminished humoral and cellular immunity directed to Omicron variants suggested that these KTRs have higher risk of breakthrough infection, even severe infection ( 33 , 34 ) and the heterologous mRNA vaccine with higher cellular immunity-induced capacity should be explored in KTRs ( 13 ). Recent mice experiment indicated that individuals with lower immunity response elicited by primary immunity might obtain more benefit from an Omicron-matched mRNA vaccine booster than an mRNA-1273mRNA booster ( 35 ).…”