A new study of the U.K. and South Africa variants of SARS-CoV-2 predicts that current vaccines and certain monoclonal antibodies may be less effective at neutralizing these variants and that the new variants raise the specter that reinfections could be more likely.
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.
Source: https://www.cuimc.columbia.edu/node/23354
Journal article: https://www.nature.com/articles/s41586-021-03398-2
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