Emerging SARS-CoV-2 Variants: Are mRNA Vaccines still Effective?

SARS-CoV-2 was first identified in Wuhan, China, in December 2019. Since then, rapid worldwide spread resulted in a global pandemic. In the midst of battling the original threat, the identification of new SARS-CoV-2 variants is alarming scientists, health officials, and the general public alike. While effective vaccines are finally available, new SARS-CoV-2 variants are raising concerns about potential viral escape.

At least three main new variants have been well identified, with some in circulation since September 2020. Below we look at the mutations involved and their potential impact on SARS-CoV-2 virulence and vaccine efficacy.

B.1.1.7 variant- This variant was first detected in the UK during September 2020 and has since spread to other countries. The USA reported the first case of this variant in December 2020. A greater transmission rate has been reported for this variant, and based on a NERVTAG note on B.1.1.7 severity by Horby et al. 2021, this variant of SARS-CoV-2 may be more virulent. A total of seventeen mutations have been identified in this variant, including eight within the Spike protein. Within Spike's RBD region, the mutation N501Y is of more concern for its potential impact on vaccine efficacy. However, recent work by Wu et al. 2021, confirmed that Moderna mRNA-1273 vaccine's effectiveness against this variant is not reduced. Similarly, Muik et al., 2021, showed that sera derived from BioNTech-Pfizer mRNA vaccine BNT162b2 recipients effectively neutralized the B.1.1.7 variant.

B.1.315 variant- First detected in South Africa during October 2020, this variant has been additionally identified in Zambia (December 2020) and the USA. Similar to B.1.1.7, this variant is characterized by an increased rate of transmission. Tegally et al. 2020, identified over ten mutations in this variant, including a potential deletion at positions 242-244. Within the Spike's RBD domain, this variant shares the N501Y mutation present in B.1.1.7. Additionally, two other mutations were identified, including E484K and K417N. Recently, Wu et al. 2021 analyzed the neutralizing activity of sera from Moderna mRNA-1273 immunized participants against the full-set of B.1.315 associated Spike mutations. A pseudovirus neutralizing assay showed a 6.4 fold reduction in neutralizing capacity. Albeit this reduction, neutralizing antibody titer in sera from mRNA-1237 recipients retained significant activity and was protective.

P.1 variant- Detected in travelers from Brazil just arriving in Japan in December 2020 and recognized as a descendent from the B.1.1.28 variant. The P.1 lineage was associated with high attack rates in northern Brazil during December 2020. Several mutations, such as E484K, K417T, and N501Y, parallel mutations evolving independently in other variants (Faria et al., 2021). This variant was recently identified in the USA.

So far, antibody responses elicited by Moderna and BioNTech-Pfizer mRNA vaccines have proved strong enough to remain protective against emerging SARS-CoV-2 variants. Taking advantage of their mRNA platform's flexibility, Moderna CEO, Stephane Bancel, in a recent press release, affirmed their efforts to develop a booster candidate to target the B.1.315 variant specifically. Additional reassurance may come from the fact that immunity is multifactorial and doesn't rely exclusively on antibody titers. Earlier studies showed that Moderna and BioNTech-Pfizer mRNA vaccines also induced strong T cell responses (Anderson et al. 2020, Sahin et al.2020).

Reference

Anderson, E. J. et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N. Engl. J. Med.(2020) doi:10.1056/nejmoa2028436.

Faria, N. et al. Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings - SARS-CoV-2 coronavirus / nCoV-2019 Genomic Epidemiology - Virological. virological.org (2021).

Muik, A. et al. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine–elicited human sera. (2021) doi: 10.1126/science.abg6105.

Sahin, U. et al. BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans. medRxiv (2020) doi: https://doi.org/10.1101/2020.12.09.20245175.

Tegally, H. et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. Preprints (2020). doi: https://doi.org/10.1101/2020.12.21.20248640.

Wu, K. et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. (2021) bioRxiv 2021.01.25.427948. doi: https://doi.org/10.1101/2021.01.25.427948.