Study of coronavirus variants predicts virus evolving to escape current vaccines
Columbia University Irving Medical
Center
The study was published in Nature on
March 8, 2021. A preprint of the study was first posted to BioRxiv on January
26, 2021.
The study's predictions are now
being borne out with the first reported results of the Novavax vaccine, says
the study's lead author David Ho, MD. The company reported on Jan. 28 that the
vaccine was nearly 90% effective in the company's U.K. trial, but only 49.4%
effective in its South Africa trial, where most cases of COVID-19 are caused by
the B.1.351 variant.
"Our study and the new clinical trial data show that the virus is traveling in a direction that is causing it to escape from our current vaccines and therapies that are directed against the viral spike," says Ho, the director of the Aaron Diamond AIDS Research Center and the Clyde'56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons.
"If the rampant spread of the
virus continues and more critical mutations accumulate, then we may be
condemned to chasing after the evolving SARS-CoV-2 continually, as we have long
done for influenza virus," Ho says. "Such considerations require that
we stop virus transmission as quickly as is feasible, by redoubling our
mitigation measures and by expediting vaccine rollout."
After vaccination, the immune system
responds and makes antibodies that can neutralize the virus.
Ho and his team found that
antibodies in blood samples taken from people inoculated with the Moderna or
Pfizer vaccine were less effective at neutralizing the two variants, B.1.1.7,
which emerged last September in England, and B.1.351, which emerged from South
Africa in late 2020. Against the U.K. variant, neutralization dropped by
roughly 2-fold, but against the South Africa variant, neutralization dropped by
6.5- to 8.5-fold.
"The approximately 2-fold loss
of neutralizing activity against the U.K. variant is unlikely to have an
adverse impact due to the large 'cushion' of residual neutralizing antibody
activity," Ho says, "and we see that reflected in the Novavax results
where the vaccine was 85.6% effective against the U.K. variant."
Data from Ho's study about the loss
in neutralizing activity against the South Africa variant are more worrisome.
"The drop in neutralizing
activity against the South Africa variant is appreciable, and we're now seeing,
based on the Novavax results, that this is causing a reduction in protective
efficacy," Ho says.
The new study did not examine the
more recent variant found in Brazil (B.1.1.28) but given the similar spike
mutations between the Brazil and South Africa variants, Ho says the Brazil
variant should behave similarly to the South Africa variant.
"We have to stop the virus from
replicating and that means rolling out vaccine faster and sticking to our
mitigation measures like masking and physical distancing. Stopping the spread
of the virus will stop the development of further mutations," Ho says.
The study also found that certain
monoclonal antibodies used now to treat COVID patients may not work against the
South Africa variant. And based on results with plasma from COVID patients who
were infected earlier in the pandemic, the B.1.351 variant from South Africa
has the potential to cause reinfection.
New study contains comprehensive
analysis of variants
The new study conducted an extensive
analysis of mutations in the two SARS-CoV-2 variants compared to other recent
studies, which have reported similar findings.
The new study examined all mutations
in the spike protein of the two variants. (Vaccines and monoclonal antibody
treatments work by recognizing the SARS-CoV-2 spike protein.)
The researchers created SARS-CoV-2
pseudoviruses (viruses that produce the coronavirus spike protein but cannot
cause infection) with the eight mutations found in the U.K. variant and the
nine mutations found in the South African variant.
They then measured the sensitivity
of these pseudoviruses to monoclonal antibodies developed to treat COVID
patients, convalescent serum from patients who were infected earlier in the
pandemic, and serum from patients who have been vaccinated with the Moderna or
Pfizer vaccine.
Implications for monoclonal antibody
treatments
The study measured the neutralizing
activity of 18 different monoclonal antibodies -- including the antibodies in
two products authorized for use in the United States.
Against the U.K. variant, most
antibodies were still potent, although the neutralizing activity of two
antibodies in development was modestly impaired.
Against the South Africa variant, however, the neutralizing activity of four antibodies was completely or markedly abolished.
Those antibodies include bamlanivimab (LY-CoV555, approved for use in the United States) that was completely inactive against the South Africa variant, and casirivimab, one of the two antibodies in an approved antibody cocktail (REGN-COV) that was 58-fold less effective at neutralizing the South Africa variant compared to the original virus.
The second antibody in
the cocktail, imdevimab, retained its neutralizing ability, as did the complete
cocktail.
"Decisions of the use of these
treatments will depend heavily on the local prevalence of the South Africa and
Brazil variants," Ho says, "highlighting the importance of viral
genomic surveillance and proactive development of next-generation antibody
therapeutics."
Reinfection implications
Serum from most patients who had
recovered from COVID earlier in the pandemic had 11-fold less neutralizing
activity against the South Africa variant and 4-fold less neutralizing activity
against the U.K. variant.
"The concern here is that
reinfection might be more likely if one is confronted with these variants,
particularly the South Africa one," Ho says.
