New mutations raise specter of ‘immune leak’



[ad_1]

ScienceCOVID-19 reports are supported by the Pulitzer Center and the Heising-Simons Foundation

Integrated image

Relatives attend the funeral of a COVID-19 victim in Manaus, Brazil on January 13.

PHOTO: MICHAEL DANTAS / AFP / GETTY IMAGES

When the number of COVID-19 cases started to rise again in Manaus, Brazil in December 2020, Nuno Faria was stunned. The virologist from Imperial College London had just co-authored an article in Science estimating that three-quarters of the city’s residents had already been infected with SARS-CoV-2, the pandemic coronavirus – more than enough, it seemed, for herd immunity to develop. The virus should be done with Manaus. However, hospitals were filling up again. “It was difficult to reconcile those two things,” says Faria. He started looking for samples he could sequence to find out if changes in the virus could explain the resurgence.

On January 12, Faria and her colleagues published their first findings on virological.org. Thirteen of the 31 samples collected in mid-December in Manaus were found to be part of a new viral line which they called P.1. Much more research is needed, but they say one possibility is that in some people, P.1 escapes the human immune response triggered by the lineage that ravaged the city earlier in 2020.

Emerging variants of the coronavirus have been in the news since scientists sounded the alarm on B.1.1.7, a variant of SARS-CoV-2 that first caught the attention of scientists in England in December and which is more transmissible than previously circulating viruses (ScienceJanuary 8, p. 108). But now they’re also focusing on a potential new threat: variants that could bypass the human immune response. Such ‘immune breakouts’ could mean that more people who have had COVID-19 remain susceptible to re-infection and that proven vaccines may, at some point, need an update.

At a meeting of the World Health Organization (WHO) on January 12, hundreds of researchers debated the most important scientific questions raised by the wave of new mutations. The WHO also convened its COVID-19 emergency committee on January 14 to discuss the impact of the new variants and the travel restrictions many countries are imposing to contain them. The committee called for a global effort to sequence more SARS-CoV-2 genomes to help track mutations.

The most transmissible variant, B.1.1.7, is already spreading rapidly in the UK, Ireland and Denmark, and probably in many other countries. But scientists are equally worried about the 501Y.V2, a variant detected in South Africa. Some of the mutations it carries, including those named E484K and K417N, alter its surface protein, its peak, and have been shown in the laboratory to reduce the ability of monoclonal antibodies to fight the virus. In a preprint published earlier this month, Jesse Bloom, evolutionary biologist at the Fred Hutchinson Cancer Research Center, showed that E484K also reduced the potency of some donors’ recovery sera by 10 – although he quickly adds that that doesn’t necessarily mean the mutation would drop people’s immunity to the new strain by ten.

P.1 adds to the concerns as it appears to have touched a similar constellation of mutations and emerged in a location with a high level of immunity. “Anytime you see the same mutations happening and starting to spread multiple times, in different strains of the virus around the world, that’s very strong evidence that there is an evolutionary benefit to these mutations,” Bloom says.

Like B.1.1.7, the Brazilian variant is already in motion. As Faria finished his analysis of Brazilian genomes, a report was published on a variant detected in travelers arriving in Japan from Brazil – and it turned out to be P.1. (As Science went to press, U.S. researchers have also reported several new variants, but their significance is unclear.)

HOW ARE THESE NEW the variants affect the course of the pandemic is unclear. In Manaus, for example, P.1 might have nothing to do with the new outbreak of infections; People’s immunity could simply wane, according to University of Oxford epidemiologist Oliver Pybus. Or it might stimulate the boost because it is transmitted more easily, like B.1.1.7, not because it can evade the immune response. “Of course, it could also be a combination of these factors,” Pybus says.

Likewise, in a recent modeling study, researchers at the London School of Hygiene & Tropical Medicine calculated that South Africa’s 501Y.V2 variant may be 50% more transmissible but not better at evading immunity. , or just as transmissible as the previous variants but able to escape. immunity in one in five previously infected people. “Reality may lie between these extremes,” the authors wrote.

Ester Sabino, molecular biologist at the University of São Paulo, São Paulo, launched a study to find re-infections in Manaus that could help decide between these hypotheses for P.1. Laboratory studies on the variants are also underway. On January 15, the UK launched a new consortium, G2P-UK (for ‘genotype to phenotype-UK’), led by Wendy Barclay of Imperial College London, to study the effects of emerging mutations in SARS- CoV-2. One idea debated at the January 12 WHO meeting is to create a biobank that would facilitate studies by housing virus samples, as well as plasma from vaccinated and recovered patients.

Interactions between new mutations can make it more difficult to determine their effects. The UK, South Africa, and Manaus variants all share a mutation called N501Y, for example, or Nelly, as some researchers call it. But the mutation, which affects the spike protein, also occurs in some variants that don’t spread faster, suggesting that N501Y doesn’t work on its own, says Kristian Andersen of Scripps Research: “Nelly may be innocent, except maybe when she’s with her bad friends. “

Bloom believes none of the changes will allow the virus to completely evade the immune response. “But I would expect these viruses to have some advantage when a large part of the population is immune” – which could help explain the skyrocketing Manaus.

SO AWAY THE VIRUS does not appear to have become resistant to COVID-19 vaccines, says vaccinologist Philip Krause, who chairs a WHO working group on COVID-19 vaccines. “The bad news is that the rapid evolution of these variants suggests that while it is possible for the virus to evolve into a vaccine-resistant phenotype, it may happen sooner than we wish,” he adds. . This possibility adds to the urgency of putting in place good surveillance to detect such escape variants early on, explains biostatistician Natalie Dean of the University of Florida.

Integrated image

People line up to receive COVID-19 vaccine in Birmingham, UK

PHOTO: JACOB KING / PA WIRE / BLOOMBERG / GETTY IMAGES

Some scientists fear that proposed changes in vaccine dosing regimens may accelerate the evolution of these strains. Desperate to tame a massive outbreak of cases, the UK decided on December 30 to allow up to 12 weeks between the first and second dose of two licensed vaccines, rather than the 3 or 4 weeks used in clinical trials vaccines, so the sooner people can get their first dose and have at least some immunity. And the Trump administration decided to ship all available doses immediately, rather than withholding 50% to ensure people get their second doses on time. The policy, which the Biden administration has said it will follow, could inadvertently extend the dosing interval if future vaccine shipments do not arrive or are not administered on time.

Widespread delays in the second dose could create a pool of millions of people with enough antibodies to slow the virus down and avoid getting sick, but not enough to clear it. This just might be the perfect recipe for creating vaccine resistant strains, says virologist Florian Krammer of Icahn School of Medicine in Mount Sinai: “If we end up with a single dose with no dose available for a quick boost, this in my opinion be a problem.

But others say the uncontrolled spread of the virus poses greater risks. “It’s carnage out there,” says evolutionary microbiologist Andrew Read of Pennsylvania State University, University Park. “Twice as many people with partial immunity must be better than full immunity in half of them.” Historically, few viruses have successfully evolved vaccine resistance, with the notable exception of seasonal influenza, which evolves so rapidly on its own – without vaccine pressure – that it requires a new vaccine every year.

If vaccine resistant strains of SARS-CoV-2 emerge, the vaccines may need to be updated. Several vaccines could be easily modified to reflect the latest changes, but regulators might be reluctant to allow them without seeing updated data on safety and efficacy, Krause says. If new variants circulate alongside older strains, multivalent vaccines, effective against multiple lineages, may even be needed. “To be clear: these are downstream considerations,” Krause says. “The public shouldn’t think it’s imminent and that new vaccines will be needed.” But Ravindra Gupta, a researcher at the University of Cambridge, says manufacturers should start producing vaccines designed to generate immunity against the mutated versions of the spike protein, as they keep appearing. “It tells us that we should have these mutations in our vaccines, so that you cut off one of the pathways for the virus to go away.”

Right now, increased transmissibility is the biggest concern, says virologist Angela Rasmussen of Georgetown University. “I wonder why [that] doesn’t play a bigger role in the conversation, ”she said. The US hospital system, she says, “is at full capacity in many places and further increases in transmission can tip us to where the system is collapsing. Then we’ll start to see potentially huge increases in mortality. “

[ad_2]

Source link