Like any other virus, SARS-CoV-2 constantly mutates, so the emergence of a number of significant variants comes as little surprise. Researchers have been puzzled by the speed of development of variants with a high number of mutations, particularly in the spike protein, however. The vaccines currently authorized in the U.S. and those likely to become available soon all target the spike protein. Have the mutations rendered them ineffective?
The answer is “No.”
Three variants of concern have grabbed researchers’ attention because of their rapid spread and apparent increased infectivity: B.1.1.7 (also known as the UK variant), B.1.351 (the South African variant), and P.1 (from the B.1.1.28 lineage, also called the Brazilian variant).
According to the CDC, reports have found “no evidence to suggest that [B.1.1.7] variant has any impact on . . . vaccine efficacy.” That variant is expected to be the dominant strain in the U.S. in March.
B.1.351 has also begun to spread more widely in the U.S. Two letters recently published in The New England Journal of Medicine evaluated the effectiveness of sera from patients immunized with either of the two vaccines with FDA authorization against genetically engineered recombinant viruses that exhibited the full set of mutations seen in the B.1.351 variant or subsets of those mutations.
In one letter, it was noted that sera from 15 vaccinated participants in the Pfizer-BioNTech phase III trial neutralized all the viruses with B.1.351 variant mutations in the spike protein. The in vitro testing indicated that there was a reduction of about two-thirds in neutralization of virus in the B.1.1351 variant mutations compared with an early sample from Washington State and to the variant (D614G) that has been dominant worldwide since March 2020.
While that may sound alarming, two points are worth noting. First, the Pfizer-BioNTech vaccine has a remarkable efficacy of 95% against the most common variant. A two-thirds reduction could well continue to protect against serious illness and death, as seen with the influenza vaccine. Second, “we know that other aspects of the immune response—including cellular immunity (memory cells, killer T-cells and so on)—are also important in the response to this virus. And we do not know if a particular level of neutralising antibodies in such laboratory tests below which we have reduced immunity to the virus,” said Peter English, consultant in communicable disease control and former editor of Vaccines in Practice.
The second letter outlined results from a study of the effectiveness of the Moderna vaccine against pseudoviruses with the spike protein from the original isolate and the D614G, B.1.1.7, and B.1.351 variants as well as some other variants. They found that both the full set of mutations in B.1.1.7 and subsets “had no significant effect on neutralization by serum obtained from participants who had received” the Moderna vaccine in clinical trials compared with the original isolate or the common variant. As with the Pfizer vaccine, the researchers said, “we observed a decrease in titers of neutralizing antibodies against the B.1.351 variant and a subset of its mutations.” Again, all the serum samples neutralized all the viruses.
While the researchers concluded that protection against the B.1.351 variant conferred by Moderna vaccine remains undetermined, others noted that the vaccine likely remained effective. “Virus neutralisation is only one of many potential mechanisms of vaccine-induced immunity. There is, as yet, no evidence that the potency of other immune mechanisms (including T cell-mediated immunity) is affected by these mutations,” said Eleanor Riley, PhD, professor of immunology and infectious disease at the University of Edinburgh.
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Published February 23, 2021
