NEWS FEATURE

Coronavirus variant threatens global recovery

A form of SARS-CoV-2 first identified in South Africa is spreading rapidly, with mutations that could stymie vaccination efforts around the world.

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The new SARS-CoV-2 variant that was first discovered in South Africa quickly spread across sub-Saharan Africa, becoming the dominant variant in many countries.Miroslav Pavicevic / Alamy Stock Photo

The new coronavirus variant that emerged in South Africa late last year and quickly spread around the world could complicate efforts to bring the COVID-19 pandemic under control.

Not only does the variant, known as B.1.351 or 501Y.V2, seem to be more infectious. Evidence is growing that its mutations may help it elude immune responses triggered by vaccines and previous infections.

At least one vaccine that South African officials had begun to stockpile has proven1 largely ineffective at preventing mild-to-moderate COVID-19 due to B.1.351. Whether that jab — the vaccine from AstraZeneca and the University of Oxford — offers any protection against severe disease caused by the new variants remains unknown. Health experts in South Africa are now debating the merits of continuing with mass immunization plans.

One leading voice in favour of a vaccine rollout is Shabir Madhi, director of the Vaccines and Infectious Diseases Analytics Research Unit at the University of the Witwatersrand in Johannesburg, who has been leading COVID-19 vaccine trials in the country.

Trials of other vaccine candidates in South Africa have demonstrated a life-saving benefit of immunization2, even though they showed decreased efficacy against B.1.351 in mild cases, he notes. Given similarities in the design of all the vaccines tested, Madhi suspects that the AstraZeneca/Oxford shot would likewise confer protection against severe illness.

In the absence of an alternative, he argues, not giving the vaccine to people at high risk of COVID-19 complications “doesn’t make much sense”.

“You’ve got a vaccine that is safe,” Madhi says. “The worst-case scenario is that the vaccine really doesn’t protect against severe disease, in which case those individuals would be topped up with another vaccine that might become available.”

A rapid spread

Houriiyah Tegally, a bioinformatician at the University of KwaZulu-Natal in Durban, agrees that large-scale vaccine distribution should remain a top priority.

She has tracked the dynamics of B.1.351 and seen how quickly new variants can spread. “We’re kind of seeing Africa being left behind,” Tegally says. “There needs to be higher attention paid to vaccinating the continent if we don’t want worrying variants to evolve.”

She and her colleagues — led by Tulio de Oliveira, director of the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP) — first detected the B.1.351 variant in mid-October 2020 in the Eastern Cape Province of South Africa. The variant then quickly moved into neighbouring provinces, becoming the dominant lineage at a time of spiking case counts in the country.

Genomic and epidemiological analyses, described3 by the KRISP team this month in Nature, found that the variant had an adaptive advantage over other forms of SARS-CoV-2, because of increased transmissibility, better immune evasion tactics, or both.

Those traits probably explain why B.1.351 has overtaken other variants in nearly all of southern Africa — with corresponding surges in infections. Zambia, for example, saw its case count rise more than 16-fold in December 2020, just as researchers first detected the variant and found that it quickly accounted for nearly all infections4.

“The levels were stunning,” says Daniel Bridges, a Lusaka-based biochemist with the public health nonprofit PATH, who led the Zambian study. “It’s looking like B.1.351 is dominant.”

A similar trend is seen in Botswana, Lesotho, Mozambique and Zimbabwe, according to publically available sequence data. Worldwide, more than 60 countries have reported cases of B.1.351 to date.

“It’s spreading very fast,” says Tapfumanei Mashe, a molecular epidemiologist at the National Microbiology Reference Laboratory in Harare, who identified the B.1.351 variant in 69% of viral samples sequenced in December 2020 and 95% of samples analyzed in January 2021ref.5. Now, he is concerned about the impact of the variant on vaccination campaigns.

Compromised immunity

Laboratory tests on the B.1.351 variant have found it to be more resistant to antibodies produced by current vaccines or antibodies from the blood of previous COVID-19 patients felipe caparros cruz / Alamy Stock Photo

All vaccines evaluated so far in South Africa have proven to be less effective against the B.1.351 variant than they were against other variants elsewhere — and laboratory experiments show one reason why. In a test tube, B.1.351 is markedly more resistant to neutralization compared to other variants, either from therapeutic antibody drugs, antibodies found in the blood of COVID-19 survivors6 or antibodies elicited by vaccines now in wide distribution7,8,9.

Those are ominous findings, but as Mashe points out, all relevant lab and field studies performed to date have involved vaccine platforms in which just part of the virus — namely, the spike protein or its coding sequence — is used to teach the immune system how to recognize and attack SARS-CoV-2.

B.1.351, with its eight mutations in the spike protein, including three in the critical receptor-binding domain, seems especially adept at circumventing those types of spike-centric, vaccine-induced defences. Yet, whether the variant equally hobbles other vaccine platforms — such as those built around killed versions of the entire virus particle — remains to be seen.

Three such inactivated virus vaccines are now approved for use in Zimbabwe, where health officials have already begun to vaccinate tens of thousands of people. In theory, “you’ve got the whole virus there, so you’re likely to have a range of antibodies” against targets outside the spike protein, notes Naor Bar-Zeev, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who works on vaccination campaigns in Africa.

“What we don’t know is whether, in practice, this is true,” says Mashe.

Broad protection

One potential upside of the new variant is that an infection with B.1.351 seems to elicit antibodies that are active against both original and newly emerging forms of SARS-CoV-2, even though the inverse is not necessarily true10.

Penny Moore, a virologist at the National Institute for Communicable Diseases in Johannesburg, suspects that the immune system recognizes B.1.351 differently than it does other variants, leading to the induction of antibodies that act at sites shared broadly across different viral lineages. “It’s entirely possible that the targeting has fundamentally shifted.”

That could bode well for efforts to develop new vaccines or more effective therapeutic antibodies. With a little tweaking to take B.1.351 into consideration, current countermeasures can be modified and may yet put an end to the pandemic.

But as Tegally points out, “more mutations are cropping up.”

Just as Africa gave the world its most worrisome variant documented to date, the region remains “a breeding ground” for next-generation variants to come — that is, unless the global health community makes the COVID-19 response in Africa a greater priority.

References

  1. 1.

    Madhi, S.A. et al. N. Engl. J. Med. (2021).

  2. 2.

    Shinde, V. et al. medRxiv (2021).

  3. 3.

    Tegally, H. et al. Nature (2021).

  4. 4.

    Mwenda, M. et al. MMWR Morb. Mortal. Wkly Rep. 70, 280-282 (2021).

  5. 5.

    Mashe, T. et al. Lancet Microbe (2021).

  6. 6.

    Wibmer, C.K. et al. Nature Med. (2021).

  7. 7.

    Wang, P. et al. Nature (2021).

  8. 8.

    Garcia-Beltran, W.F. et al. Cell (2021).

  9. 9.

    Planas, D. et al. Nature Med. (2021)

  10. 10.

    Cele, S. et al. Nature (2021).

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