LONDON – There’s mixed news about emerging variants of SARS-CoV-2, with Pfizer Inc. and Biontech SE reporting their vaccine Comirnaty maintains its protective effect against B 1.1.7, first detected in the U.K., while researchers in South Africa say virus variant 501Y.V2 is able to escape neutralization by both monoclonal antibodies and convalescent plasma from previously infected individuals.
The B.1.1.7 lineage that was picked up by viral genome sequencing in the U.K. on Dec. 11, 2020 was the first to raise the alarm about possible escape variants. It has since been detected in 60 countries worldwide, according to the latest epidemiological summary from the World Health Organization.
B.1.1.7. has 10 mutations that alter amino acids in the spike protein that is encoded for by most COVID-19 vaccines. In a non peer-reviewed paper on the preprint server Biorxiv, Pfizer and Biontech report generating a replication deficient pseudovirus featuring all 10 mutations.
Sera taken from 16 participants in the phase I/II study of Comirnaty 21 days after receiving the second dose, neutralized the pseudovirus in a range regarded as biologically equivalent to the reference strain of SARS-CoV-2 from Wuhan, China, against which the vaccine was designed.
“Neutralization of the pseudovirus bearing the U.K. [variant] spike [protein] by [Comirnaty] immune sera makes it likely that COVID-19 caused by the U.K. virus variant will also be prevented by immunization with [Comirnaty],” the researchers say.
However, further studies are needed to keep assessing the vaccine’s effectiveness in preventing COVID-19 caused by other new virus variants, they add.
In addition, it is not known yet what reduction in neutralizing power might indicate a need to modify Comirnaty. Pfizer and Biontech said if a change is required to address virus variants in future, the mRNA platform technology on which it is based is flexible enough to make that adjustment.
“This is a reassuring result, but doesn’t address the effect of current vaccines on infection with other variant viruses, including those identified in South Africa and Brazil,” said Lawrence Young, a virologist and professor of molecular oncology at Warwick University medical school. However, the report does reinforce the flexibility of mRNA-based vaccine technology to be rapidly adapted to accommodate changes in the virus, he noted.
Pfizer and Biontech previously published data from an in vitro study that evaluated the N501Y mutation in B1.1.7, which also occurs in the spike protein of the 501Y.V2 variant that is causing concern in South Africa.
That showed efficient neutralization by plasma of 20 people who took part in the phase I/II study of Comirnaty.
The more recent research carried out on 501Y.V2 by the National Institute for Communicable Diseases in South Africa is more concerning, showing the variant is able to escape neutralization by monoclonal antibodies, including those being used to treat COVID-19 patients, and by convalescent plasma from previously infected individuals.
High levels of resistance to convalescent plasma were observed in 21 of 44 samples of the variant.
Brazil variant likely resistant, too
501Y.V2 escapes neutralizing antibody responses due to the E484K and K417N mutations. These mutations do not occur in B1.1.7 but are seen in the latest SARS-CoV-2 variant reported from Brazil.
Along with two cases of reinfection that have been reported from Brazil, that suggests the Brazil variant also is likely to exhibit significant levels of neutralization resistance, Young said. “It is important that we now determine the neutralizing ability of antibodies against virus variants generated in response to vaccination and study the immune response in individuals infected with virus variants,” he said.
Julian Tang, honorary professor and clinical virologist in respiratory sciences at Leicester University noted that the convalescent plasma results, based on natural infection and exposure to the whole virus and all its proteins, did show considerable binding to the 501Y.V2 variant via non-neutralising antibodies. That can “still offer some significant protection against this virus variant,” he said.
The South African researchers also acknowledge they have not assessed the effect of the variant on T-cell responses. “Some additional defence will arise from this, as well as other naturally existing innate components of the immune system in those infected, in addition to any residual vaccine protection,” said Tang.
“Further real life studies will be needed to assess the true impact of this South African 501Y.V2 variant on the vaccinated South African population outside of a laboratory context, and in the presence of other natural human immune responses,” he said.