Recent genetic mutations to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins have given rise to new variants, causing a great deal of global concern. There is some evidence of vaccines working against the B.1.1.7 variant first found in the UK. However, the P.1 variant found in Brazil and the B.1351 variant first discovered in South Africa have the K417N/T, E484K, and N501Y receptor-binding domain (RBD) mutations that escape the neutralizing effects of the vaccine and overall immune response.
Understanding how variants escape vaccine-boosted immune function is necessary to neutralizing SARS-CoV-2. An international team of researchers from the Massachusetts Institute of Technology (MIT) and Harvard University in the USA analyzed Pfizer and Moderna vaccines' effectiveness in neutralizing spike proteins from 10 different strains of SARS-CoV-2.
Here, we find that while many strains, such as B.1.1.7, B.1.1.298, or B.1.429, continue to be potently neutralized despite the presence of individual RBD mutations, other circulating SARS-CoV-2 variants escape vaccine-induced humoral immunity,” wrote the researchers.
The study “Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity” is available as a preprint on the medRxiv* server, while the article undergoes peer review.
Analyzing globally circulating SARS-CoV-2 variants
The team collected blood serum from a cohort of young individuals with a median age of 33 years old administered either one or two doses of the mRNA vaccines from Pfizer or Moderna. They analyzed the number of neutralizing antibodies against SARS-CoV-2 pseudoviruses specially designed to mimic globally circulating strains.
Specifically, the researchers focused on the original SARS-CoV-2 virus that first emerged in Wuhan, China, along with other commonly circulating variants, including the B.1.1.7 variant, the B.1.1.298 variant first found in Denmark, the B.1.429 variant first found in the USA, the P.1 strain, the P.2 strain first found in Japan, three variants of the B.1.351 lineage, and the pre-emergent bat coronavirus WIV1-CoV.
COVID-19 variants reduce vaccine-induced immunity
The researchers found that participants who received two doses of either mRNA vaccine showed greater neutralization for the wild-type SARS-CoV-2 than those who received one vaccine dose. In addition, individuals in their 20s and 30s appeared to have higher neutralization responses than older individuals. Although, there was a slight decrease in Pfizer’s neutralization when the D616G — the dominant strain in the summer of 2020 — was present.
Having one mutation on the SARS-CoV-2 spike protein showed similar decreases in neutralization as the D4614G strain. There was a 2.3-fold decrease in Pfizer’s vaccine’s neutralizing power when the B.1.1.7 variant was present. In addition, the B.1.1.298 variant found in Danish minks showed a 3.4-fold decrease. The B.1.429 variant first found in California showed a 2.9-fold reduction in neutralizing power compared to the wild-type SARS-CoV-2.
Multiple genetic mutations escape immune function
Having the E484K mutation significantly reduced the vaccine’s ability to neutralize the spike protein. As a result, a 13.4-fold decrease in neutralizing power was observed in the P.2 variant. Having multiple mutations, such as in the P.1 strain, which holds three mutations and has shown instances of re-infection, showed a 15.1-fold decrease in Pfizer’s vaccine neutralization ability.
With a small difference, the three B.1.351 strains are similar in the P.1 strain's genetic composition but show greater resistance to vaccines’ neutralizing power. The researchers found an 84.1-fold decrease in v.2 and v.3 of the B.1.351 strain. Additionally, there was a 72.3-fold decrease in the WIV1-CoV.
For individuals who received only one dose of either vaccine, no neutralizing antibodies were present with these strains. The researchers suggest the three mutations on the spike protein are strong enough to evade vaccine-induced neutralizing antibody responses. However, while they are the major drivers of resistance, additional mutations such as those found in B.1.351 v2 amplified their ability to escape neutralization.
“Given the loss of vaccine potency against a number of circulating variants, individuals receiving a single dose of vaccine did not raise sufficient antibody titers to provide any detectable cross neutralization against B.1.351 v2 or v3,” wrote the researchers. “While our studies are limited by the relatively short follow-up time after vaccination, our findings support the importance of 2-dose regimens to achieve titers, and perhaps breadth, to enhance protection against novel variants.”
Need for booster shots to combat new variants
Taken together, our results highlight that BNT162b2 and mRNA-1273 vaccines achieve only partial cross-neutralization of novel variants and support the reformulation of existing vaccines to include diverse spike sequences,” concluded the researchers.
As the COVID-19 pandemic continues to spread and evolve, additional booster shots or repeated vaccinations may be required to ensure long-lasting immunity.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.