Persistent T cell-mediated immune responses against Omicron variants after the third COVID-19 mRNA vaccine dose

Abstract

IntroductionThe prime-boost COVID-19 mRNA vaccination strategy has proven to be effective against severe COVID-19 disease and death. However, concerns have been raised due to decreasing neutralizing antibody levels after COVID-19 vaccination and due to the emergence of new immuno-evasive SARS-CoV-2 variants that may require additional booster vaccinations.MethodsIn this study, we analyzed the humoral and cell-mediated immune responses against the Omicron BA.1 and BA.2 subvariants in Finnish healthcare workers (HCWs) vaccinated with three doses of COVID-19 mRNA vaccines. We used enzyme immunoassay and microneutralization test to analyze the levels of SARS-CoV-2 specific IgG antibodies in the sera of the vaccinees and the in vitro neutralization capacity of the sera. Activation induced marker assay together with flow cytometry and extracellular cytokine analysis was used to determine responses in SARS-CoV-2 spike protein stimulated PBMCs.ResultsHere we show that within the HCWs, the third mRNA vaccine dose recalls both humoral and T cell-mediated immune responses and induces high levels of neutralizing antibodies against Omicron BA.1 and BA.2 variants. Three weeks after the third vaccine dose, SARS-CoV-2 wild type spike protein-specific CD4+ and CD8+ T cells are observed in 82% and 71% of HCWs, respectively, and the T cells cross-recognize both Omicron BA.1 and BA.2 spike peptides. Although the levels of neutralizing antibodies against Omicron BA.1 and BA.2 decline 2.5 to 3.8-fold three months after the third dose, memory CD4+ T cell responses are maintained for at least eight months post the second dose and three months post the third vaccine dose.DiscussionWe show that after the administration of the third mRNA vaccine dose the levels of both humoral and cell-mediated immune responses are effectively activated, and the levels of the spike-specific antibodies are further elevated compared to the levels after the second vaccine dose. Even though at three months after the third vaccine dose antibody levels in sera decrease at a similar rate as after the second vaccine dose, the levels of spike-specific CD4+ and CD8+ T cells remain relatively stable. Additionally, the T cells retain efficiency in cross-recognizing spike protein peptide pools derived from Omicron BA.1 and BA.2 subvariants. Altogether our results suggest durable cellmediated immunity and protection against SARS-CoV-2.

Humoral and cellular response three months following bivalent booster administration

“…A signi cant boost in the percent of spike-speci c CD8 + and CD4 + T cells was also observed after the booster in the study of Naaber et al, with 100% and 90% of subjects positive for spike-speci c CD8 + and CD4 + T cells (44). Three months after the booster, the cellular response slowly decreased but the difference was non-signi cant (44), an observation also made by Belik et al (45). Contrariwise, Maringer et al identi ed that the spike-speci c T cell responses (i.e., IFNγ by ELISpot) after different COVID-19 vaccination regimens were not further enhanced by booster vaccination, suggesting that booster vaccination was of particular relevance to increase the antibody response but the population was limited (n = 13) (17).…”

Feline Infectious Peritonitis mRNA Vaccine Elicits Both Humoral and Cellular Immune Responses in Mice

“…Of particular importance in the cat, the LNP itself serves as the adjuvant, negating the need for more traditional adjuvants that can be associated with the development of feline injection site sarcomas. Additionally, increasing epidemiologic evidence is emerging to suggest that the initial series of mRNA vaccination can yield a robust and long-lasting memory T and B cell response [48][49][50][51]. Taken together, these properties make mRNA vaccines a highly promising strategy to address infectious diseases for which no safe and effective vaccine exists in veterinary medicine.…”

T cell immunity following COVID-19 vaccination in adult patients with primary antibody deficiency – a 22-month follow-up

“…There have been relatively few studies following long-term immune responses in immunocompromised patients. In immunocompetent individuals, mRNA vaccines have been shown to induce the formation of memory T cells: CD4+ cells mainly of effector memory (T EM ) and central memory (T CM ) phenotypes and CD8+ cells of CD45RA+ expressing effector memory (T EMRA ) phenotype ( 30 , 31 ). In the present study, we carried out a systematic follow-up of humoral and cellular immune responses after four COVID-19 vaccinations for up to 15 months.…”