Severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) emerged in Wuhan, China in 2019 and caused coronavirus disease 2019 (COVID-19) and more than 1.4 million deaths, as of July 22, 2021.¹ Severe form of infection is associated with respiratory distress syndrome, pneumonia, myocarditis, renal injury, gastrointestinal, testicular, ophthalmic, central-nervous-system diseases, etc.² SARS-CoV-2, spherical form, diameter of 125 nm., and a single positive-strand-ribonucleic acid (RNA) is rapidly spread in animals and humans.³ S-protein of the surface of virus is most important for virus-host cell binding, fusion and host cell entry through the cellular Angiotensin Converting Enzyme 2 (ACE2) and finally infect the host cell,⁴ in addition to the sixteen non-structural proteins, and eight accessory proteins.⁵

In previous animal studies, protection from SAR-CoV-2 (COVID-19) infection contributed from both cellular and humoral immune responses. Most COVID-19 mRNA vaccine studies have concentrated on post-immunization-humoral-response characterization.^6–10 Alpha, Delta variant strains, and original Wuhan strain contributes an association between protection against COVID-19 and antibody (humoral) level, detected by previous studies.^11–13 With greater magnitude of CD4+ cells, compared with CD8+ T cells, persist-at-least-6-month-post-immunization-SARS-CoV-2-mRNA-vaccine-induced-cellular-immunity was evidenced by SARS-CoV-2-Spike-specific CD8+ and CD4+ T cells.^14–16 Both cellular and humoral SARS-CoV-2 Spike Specific immune responses of the adaptive immune system rises with each vaccine dose, whereas progressively reduce with higher comorbidity prevalence and older age (Figure 1).¹⁷ A previous study demonstrated lower spike-protein antibody levels in individuals with medical conditions and those with 50 years of age and older in double Sino pharm vaccinated group, whereas a booster dose of Pfizer/BioNTechBNT162b2 vaccine critically increased spike-protein antibody levels.¹⁸

Figure 1

1. SARS-CoV-2 Spike-specific CD4 + T cells at day 0 (blue), 21 (red), and 90 (brown) (n = 286, 460, and 462, respectively). 
2. SARS-CoV-2 Spike-specific CD8 + T cells at day 0 (blue), 21 (red), and 90 (brown) (n = 272, 444, and 449, respectively). Data was compared using unpaired, non-parametric Mann–Whitney U-test. Error bars show the distribution within 1.5 times IQR.¹⁷

In conclusion, overall cross-reactive T cell responses against different SARS-CoV-2-variants of concern (VOC) in both previously infected and infection-naïve HCWs. For different VOC, COVID-19 booster vaccinations induce neutralizing antibody and strong T cell responses and the presence of T cell responses against SARS-CoV-2 VOC indicate that vaccine-induced T cell immunity contributes cross-reactive protection.

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Author declares that there is no conflict of interest.

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