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

The 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. Here we show that within the vaccinated health care workers (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, Th1-type memory CD4+ T cell responses are maintained for at least 7 months post the second dose and 3 months post the third vaccine dose suggesting durable immune protection.

Comparative analysis of BNT162b2, mRNA-1273 and ChAdOx1 COVID-19 vaccine induced antibody responses and the 3rd BNT162b2 vaccine induced neutralizing antibodies against Delta and Omicron variants (preprint)

Two COVID-19 mRNA and two adenovirus vector vaccines have been licensed in Europe and various vaccine combinations and dosing strategies have been exploited to maximize the immunity against COVID-19. Here, we show that among health care workers (n=328) two doses of BNT162b2, mRNA-1273, or ChAdOx1 as also a combination of an adenovirus vector and mRNA vaccines induces equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against B.1 and B.1.617.2 when administrated with a long 12-week dose interval. Two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies compared to the long interval. Third mRNA vaccine dose for the short dose interval group increased the antibody levels 4-fold compared to the levels after the second dose. Importantly, sera from all three-times vaccinated neutralized B.1.1.529 (Omicron). The data indicates that a third COVID-19 mRNA vaccine dose efficiently induces cross-protective neutralizing antibodies against multiple variants.