Vaccines vs variants: An ongoing race

What does the rapid spread of SARS-CoV-2 variants that affect vaccine potency mean for the fight against COVID-19?

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As emerging COVID-19 ‘variants of concerns’ and mutations cause surges of infections around the world, pharmaceutical companies and researchers are racing to update and adapt their vaccines. The future may be unclear, but some scientists say the unprecedented scale of vaccine development and global collaboration give reason for hope.

A myriad of COVID-19 vaccines were produced at record speed and authorized for emergency use, including mRNA-type vaccines and adenovirus vector vaccines. With the emergence of variants, the idea of developing boosters or creating seasonal or variant-proof vaccines has gained urgency and momentum. 

The emergence of variants—descendent viruses with errors in their RNA and consequently a different genetic code than the original virus—has raised concerns about the effectiveness of ongoing vaccination efforts. Some vaccines seem to fare better against some variants, but there are few absolutes.

According to the US Centers for Disease Control and Prevention (CDC), last fall saw the birth of multiple variants, the most notable of which are B.1.1.7, commonly called the Alpha variant; B.1.351, the so-called Beta variant, which emerged independently from B.1.1.7; and P.1, known as the Gamma variant, which the CDC reports has 17 unique mutations, including three in the receptor binding domain of the spike protein. 

B.1.1.7 is more contagious than other known variants and is associated with increased disease severity and possibly  increased risk of death—a risk that, in late January, UK scientists were still trying to evaluate based on new analyses

Earlier this year, a medRxiv preprint—a paper that hasn’t been peer reviewed and thus has yet to be thoroughly evaluated—reported that a new variant of concern, tagged B.1.526, had been identified in New York, spreading among older and more frequently hospitalized people. The paper7 suggested that this variant has found footing in the northeast of the US. 

Scientists are now rushing to understand how these variants cross react with each other, as well as how they interact with our immune system and, more specifically, with monoclonal (or laboratory-made) antibodies as well as antibodies produced naturally as a result of infection. Understanding these dynamics is an important step towards finding ways to neutralize the variants2.  

Penny Moore is among the scientists studying the characteristics of some of these variants in relation to monoclonal antibodies. In a March 2021 study in Nature Medicine1, she was the first to show that the Beta variant B.1.351 has the ability to resist convalescent plasma and completely evade three classes of neutralizing antibodies.

When the data about B.1.351 first came out, Moore says she and her colleagues “were worried that the level of protection for people who were previously infected would be much less than we had hoped. The second major thing that we were very concerned about was that it might have implications for the efficacy of vaccines that were being rolled out in South Africa. Unfortunately, that did come to be.”

Moore’s study suggested that reinfection was possible. A Nature paper5 by Alex Sigal and others published a few weeks after Moore’s confirmed that antibodies from recovered COVID-19 patients from the first wave of the epidemic in South Africa were less effective at neutralizing B.1.351. Moore’s work also indicated that vaccines targeting the SARS-CoV-2 spike may not be as effective against emerging variants of the virus.  

A separate study led by Michael Diamond looked at how antibodies fared against several variants. The study investigated monoclonal antibodies and samples of serum from convalescent patients with COVID-19 and people who received the mRNA Pfizer-BioNTech vaccine, testing them against a panel of naturally occurring and synthetic SARS-CoV-2 variants. 

Published in Nature Medicine3 in March, the study found that current neutralizing antibodies are less effective against the Beta variant and other variants with specific mutations. The researchers recommended adjustments to the spike sequence used in some of the vaccines, as well updating monoclonal antibody cocktails to target highly conserved regions of the virus.  

A third study in Nature Medicine6 came to a similar conclusion: antibodies from people vaccinated against COVID-19 can neutralize B.1.1.7 but may partially or completely fail to neutralize B.1.351. This study used real viral strains instead of lab-engineered proxies.

It is not surprising that the coronavirus is mutating—for the virus itself, this is business as usual. “Viruses are really very good at mutating to get away from anything that impacts them negatively, and in this case, it’s neutralizing antibodies which are a subset of your antibodies,” says Moore. “There's a lot of pressure on the virus to change to get away from those.”

In fact, Moore says that SARS-CoV-2 is not particularly mutating fast, noting that it mutates much slower than HIV, which she researched for most of her career. “What creates all these opportunities for the virus to pick up these mutations is the fact that there's so many millions of people across the world who are infected.”

However, there is a silver lining to the evasive tactics of B.1.351: a person infected by the variant produces broad-range antibodies that potentially inoculate against other variants, as per Moore. This was confirmed by Sigal’s Nature study5, which demonstrated that plasma taken from patients infected with B.1.351 during the second wave of the epidemic in South Africa was effective at neutralizing the strain that circulated during the first wave.

Moore, and her colleagues are still trying to understand why antibodies from this variant are special. They are also still uncertain about how future-proof these antibodies are. “Genetically, we do not know how the virus will mutate in the future. It's a dead certainty that it will mutate, and new variants will emerge, but it is very hard to predict how that might happen,” Moore explains. 

According to Mark Zeller, who is part of the Andersen lab at the Scripps Research Institute that is investigating how viruses such as SARS-CoV-2 emerge and cause outbreaks: “We've proven that we can really make these vaccines pretty quickly. There’s a possibility that we end up in a situation where we just have to update vaccines regularly—it could even be every year,” he says. 

While the vaccine infrastructure has improved, Zeller cautions that tests of updated vaccines will have to be as elaborate as the trials of the original vaccines. “It will still take months, and then obviously [new vaccines and boosters] will have to be produced and distributed. But it can go faster than the first time around. And it almost certainly will,” he says.

Moore notes that the pandemic has led to has spurred the development of vaccines and vaccine platforms. Some platforms, such as mRNA vaccines, “are very amenable to quick switches,” she says. “But understanding how well they will work requires a little bit more work.”

References

  1. Wibmer, C.K., Ayres, F., Hermanus, T. et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med. 27, 622-625 (2021).  | article
  2. Luchsinger, L.L., Hillyer, C.D. et al. Vaccine efficacy probable against COVID-19 variants Science. Science 371, 1116 (2021) | article
  3. Chen, R.E., Zhang, X., Case, J.B. et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 27, 717-726 (2021). | article
  4. Tegally, H., Wilkinson, E., Giovanetti, M. et al. Emergence of a SARS-CoV-2 variant of concern with mutations in spike glycoprotein. Nature 592, 438-443 (2021).  | article
  5. Cele, S., Gazy, I., Jackson, L. et al. Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature 593, 142-146 (2021). | article
  6. Planas, D., Bruel, T., Grzelak, L. et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat. Med. 27, 917-924 (2021). | article
  7. Annavajhala, M.K. et al. A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York. medRxiv (2021) | article

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