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.
Reference:
Pengfei Wang et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and
B.1.1.7, Nature (2021). DOI:
10.1038/s41586-021-03398-2