Viral Variants and Vaccines

Viral mutations may naturally occur anywhere in the SARS-CoV-2 genome. Unlike the human DNA genome, which is slow to mutate, RNA viruses are able to readily, and quickly, mutate. A mutation may alter the viral function (eg, enhance receptor binding), or may have no discernable function.

The CDC predicts the B.1.1.7 variant (first detected in the United Kingdom) will be the major circulating variant in the United States by March 2021. ^[20]   

Enhanced genomic surveillance in some countries have detected other variants of concern (VOCs) including B.1.351 (501Y.V2) first detected in South Africa and the B.1.1.28 (renamed P.1) (501Y.V3) which was detected in 4 travelers from Brazil during routine screening at the Tokyo airport. ^[20]  

As of January 2021, researchers are studying how variants may or may not alter the extent of protection by available vaccines. 

The immune response provoked by vaccines includes protection from the antigen by eliciting antibodies, T-cells, and interferons. 

Variants that have emerged in the United Kingdom and South Africa in late 2020 have multiple mutations in their S glycoproteins (ie, the spike protein), which are key targets of currently available vaccines. ^[21]  

In vitro studies comparing sera of neutralizing antibody titers from participants in vaccine studies describe use of sera from BNT162b2 SARS-CoV-2 vaccine showing no reduction in neutralization of pseudoviruses bearing the B.1.1.7 variant (ie, UK variant) and the B.1.351 variant (ie, South African variant). ^[21, 22]  Similarly, the mRNA-1273 vaccine neutralizing capabilities were assessed against these variants. No significant impact on neutralization against the B.1.1.7 variant was detected in either case. A reduced, but still significant neutralization was measured against the mutations present in B.1.351. ^[23]   

A slight decreased neutralization is not considered to be clinically significant regarding vaccine efficacy, owing to the very high efficacy of each mRNA vaccine (ie, approximately 95%). Continued variant surveillance will allow foresight for any needed changes to vaccine development or future booster doses that may be warranted. 

Moderna announced its clinical strategy to proactively address the pandemic as the virus continues to evolve. The company will test an additional booster dose (ie, third dos) of its mRNA-1273 vaccine to study the ability to further increase neutralizing titers against emerging strains beyond the existing primary vaccination series. Additionally, the company is advancing mRNA-1273.351 into preclinical studies and a Phase 1 study in the United States to evaluate the immunological benefit of boosting with strain-specific spike proteins. ^[24]  

Novavax reported preliminary efficacy results for NVX-CoV2373 vaccine from the phase 3 trial in the UK (n > 15,000). Estimated vaccine efficacy was 89.3%. The UK variant was detected in over 50% of PCR-confirmed symptomatic cases (32 UK variant, 24 nonvariant, 6 unknown). The calculated efficacy was 85.6% for the UK strain and 95.6% for the original strain. ^[13]  

Preliminary data from the Phase 2b trial (n > 4,400) conducted in South Africa for NVX-CoV2373 reported 60% efficacy in the 94% of the study population that was HIV-negative. Among the 44 individuals testing positive for COVID-19, the South African escape variant was detected in 92.6% cases analyzed (25 out of 27 cases). ^[13]  

Johnson & Johnson reported phase 3 trial results (EMSEMBLE; n= 43,783) for their single-dose Ad26.COV2.S viral vector vaccine in late January 2021. The trial was conducted in geographical regions and during the time when several variants emerged.  At Day 28, the vaccine was 72% effective in the US, 66% in Latin America, and 57% in South Africa at preventing moderate-to-severe COVID-19 infection. Importantly, the vaccine was 85% effective in preventing severe disease and provided complete protection against COVID-related hospitalization and death in all geographic regions. Additionally, it showed consistent protection across all variants and regions studied, including South Africa where nearly all cases of COVID-19 (95%) were due to infection with a SARS-CoV-2 variant from the B.1.351 lineage. ^[12]