In view of the simultaneous increase of vaccine breakthrough COVID-19 cases, researchers are keen to understand the mechanism that emphasizes Delta’s ability to evade immunity. In a recent study, Wang and his colleagues from various research institutes in Singapore asked whether the antibody triggered by the BNT162b2 mRNA vaccine developed by Pfizer could provide sufficient protection against the SARS CoV-2 Delta variant.

Wang et al. started using pseudovirus detection, in which the SARS CoV-2 spike protein variant is expressed on the surface of lentivirus and used to infect cells expressing ACE-2 receptors. The effect of Spike mutation on neutralizing activity of antibody was directly tested. The researchers found that the antibody triggered by BNT162b2 mRNA vaccine was significantly weaker in neutralizing the pseudovirus carrying Delta Spike variant (37% neutralizing activity) than it was in neutralizing the pseudovirus expressing Wuhan Spike (76%).

However, these findings are inconsistent with the early study of Liu et al., which showed that the antibody induced by BNT162b2 mRNA vaccine can still neutralize most VOCs. In this study, chimeric SARS CoV-2 viruses modified to express VOC Spike sequences were used to evaluate antibody neutralizing activity in plaque reduction neutralization tests. Liu and his colleagues found that the neutralizing antibody activity against the B.1.617.2 Delta variant decreased slightly (Liu et al. 2021).

Therefore, it is still controversial whether the immune escape of SARS CoV-2 Delta variant is partly due to the decrease of antibody neutralizing activity of immunized individuals.

CD8+T cell cytotoxicity

In addition to neutralizing antibody responses, it has been determined that mRNA vaccines, such as BNT162b2, also induce protective cellular immunity, including CD4+and CD8+T cell responses (Sahin et al 2021, Painter et al 2021). Nevertheless, in individuals immunized with the mRNA vaccines of Moderna and Pfizer, T cell immunity against VOC (e.g., B.1.1.7 Alpha and B.1.351 Beta variants) has also shown a decrease (Gallagher et al., 2021). Similarly, a new study supports reducing T cell immunity to Delta variants (Zhang et al. 2021).

Since vaccine induced T cell immunity is essential to alleviate disease severity and eliminate virus, Zhang and his colleagues analyzed how mutations in several VOCs affect MHC dependent peptide presentation and T cell response (Tan et al. 2021). Synthetic peptide enabled the team to validate several SARS-CoV-2 peptides as CD8+T cell epitopes. In these validated peptides, four identified epitopes are known to mutate in different VOCs. For example, one epitope corresponds to a peptide in Spike protein, which has mutant L452R in Delta variant. Most importantly, Zhang et al. It was found that for four CD8+T cell verified epitopes, the presence of mutation significantly reduced their ability to activate T cells from individuals vaccinated with CoronaVac vaccine (Zhang et al. 2021).

For BNT162b2 mRNA vaccine, a recent study in the UK found that its effectiveness decreased to 88% in individuals who were fully vaccinated (i.e., two doses) and infected with Delta variant (Lopez Bernal et al., 2021). Nevertheless, BNT162b2 mRNA vaccine is still effective in preventing COVID-19 symptomatic diseases caused by VOC infection. In general, there is still much to be found to emphasize the molecular mechanism of immune escape of current SARS CoV-2 variants. With the emergence of more variants, understanding the potential mechanisms will help to address future immunization needs.