Are the new SARS-CoV-2 variants resistant against the vaccine?

COVID-19 has more than six known variants to date, including South Africa (B.1.351), Brazil (B.1.1.248), United Kingdom (B.1.1.7), and United States (B.1.351 and BR-B.1.1.248) variants. Each variant has 10 to 15 mutations compared with the wild type. The spike protein is the main protein in virus immunization. The spike of B.1.1.7 influences the effectiveness of antibody neutralization, and the monoclonal antibodies (mAbs) will be reduced when targeting the N-terminal domain (NTD) or receptor-binding domain (RBD). However, E484K mutation and other mutations occur near to it, such as S477N, K427N, and N501Y in RBD. This phenomenon negatively affects current vaccines and treatment. E484K can hide from different known types of mAbs, such as COV2 (3025- 2381- 2196). A mix of mAbs with the ability to target different positions in the spike protein is necessary to solve this issue and defend against any new variants that may appear in the future.[1,2]

Only the data of human sera with Pfizer-BioNTech (BNT162b2) mRNA vaccine against the two mutations E484K and N501Y are available, and they show low immunization rate, which is unexpected. How the immune system, specifically B cell, loses the activity in cases of a single mutation is unclear. The same observation occurs in the case of using immune plasma with B.1.351 and B.1.1.7 variants. B.1.351 consisting of 11 mutations will B.1.1.248 consisting of 15 mutations, and both of them share E484K and N501Y mutations. B.1.1.248 can stimulate the immune neutralization slightly better than B.1.351. The reason is that some mutations in NTD stimulate the immune neutralization. However, it may fail due to that E484K and N501Y and other unknown mutations in the RNA and the protein of the SARS-CoV-2 use the immune plasma from the recently infected portion as a treatment. According to our unpublished data, molecular dynamics on spike protein show that the six variants are more stable than the wild type (the original one that spread in China last year). In addition, how the T and B cells defend against different virus mutant types is unclear to date, especially when serum antibody responses are presented. Thus, using the method that depends on cell-based neutralization results in misdiagnosis. Moreover, the difference in producing antibody neutralization depends on which cell line reacts to which SARS-CoV-2 variants.[3,4]

All the discussions above provide insights into why re-infection occurs and highlight the problem in vaccine design. We also need to keep evaluating the currently available vaccines and accept that any of these vaccines cannot be used at any time because some antibodies lose the ability to block the recipient cells during the infection. In the end, losing the neutralization against the variants of SARS-CoV-2 remains the main problem in the field of vaccination and therapy. The epidemic can be overcome using cocktails of vaccine and antibody of all the SARS-CoV-2 protein and RNA. Further studies and measurements in our immune system, complementing proteins and receptors, vaccinations, and efficacy are required against the variants of SARS-CoV-2.