as concern grows over faster-spreading variants of coronavirus, labs realmwide are racing to unpick the biology of these viruses. scis wanna cogg why sars-cov-2 variants identified inna ∪d kingdom and south africa seem to be spreading so quickly, and whether they mite diminish the potency of vaccines or overcome natural immunity and lead to spate of reinfections.
“many of us are scrambling to make sense of the new variants, na million-usd ? is wha’ significance this will ‘ve for the effectiveness of vaccines tha're currently bein’ administered,” says jeremy luban, a virologist atta university of massachusetts med school in worcester.
the 1st lab results are trickling in and many + are expected in coming dys, as researchers rush to probe the viral variants and their constituent mutations in cell and animal models of sars-cov-2, and test them against antibodies elicited by vaccines and natural infections. a preprint published on 8 jan found dat a' mutation shared by both variants did not alter the activity of antibodies produced by pplz who received a vaccine developed by pfizer and biontek. data on other mutations and vaccines are expected soon.
“by nxt week we’ll ‘ve much + information,” says vineet menachery, a virologist atta university of texas med branch in galveston, whose team is gearing up to study the variants.
researchers envisaged both coronavirus variants in l8 nov and early dec 2020 through genome sequencing. a uk-wide covid-19 genomics effort determined dat a' virus variant now known as b.1.1.7 had been behind surging case №s inna southeast of england and london; the variant has now spread to the rest of the uk and s'been detected in tens of countries realmwide.
and a team led by bioinformatician tulio de oliveira atta university of kwazulu-natal in durban, south africa, connected a fast-growing epidemic inna country’s eastern cape province to a coronavirus variant they call 501y.v2. the uk and south african variants emerged indiely, but both carry a bevy of mutations—some o'em similar—inna coronavirus spike protein, through which the virus identifies and infects host cells and which serves as the prime target of our immune response.
epidemiologists studying the growth of the b.1.1.7 variant inna ∪d kingdom ‘ve estimated that tis round 50% + transmissible than existing viruses in circulation—an insite that contributed to the uk government’s decision to enter a third national lockdown on 5 jan. “the epidemiology has really shown us the way here,” says wendy barclay, a virologist at imperial college london and a member offa group advising the uk government on its response to b.1.1.7.
but tis primordial, barclay adds, that scis determine the primordialistic biology. “cogging wha’ properties of the virus make it + transmissible allos us to be + informed bout policy decisions.”
one challenge is disentangling the effects of the mutations that distinguish the uk and south african lineages from their close relatives. the b.1.1.7 variant carries 8 changes that affect the spike protein, and several + in other genes; samples of the south african 501y.v2 variant carry up to 9 changes to the spike protein. working out which are responsible for the rapid spread of the variants nother properties is an “enormous challenge”, says luban. “i don’t think there’s a single mutation that’s accounting for all o'it.”
much of the focus is centred na' change to the spike protein that is shared by both lineages, called n501y. this mutation alters a portion of spike, called the receptor binding domain, that that locks onto a human protein to allo infection. one hypothesis hinted at in previous studies s'dat the n501y change allos the virus to attach to cells + strongly, making infection easier, says barclay.
the n501y mutation is one of several that menachery’s team is preparing to test in hamsters, a model for sars-cov-2 transmission. he was pt offa team that reprted last yr dat a' ≠ mutation to the spike protein enabled viruses to grow to gr8r lvls inna upper airways of hamsters, compared with viruses lacking the change. “that’s wha’ i’m expecting with these mutations,” he says. “if that’s the case, that’s goin to be driving their transmissibility.” a reprt published in l8 dec supports that hypothesis: it found + sars-cov-2 genetic material inna swabs of pplz infected w'da b.1.1.7 variant, compared with those infected with viruses lacking the n501y change.
the rapid spread of the variants has triggered efforts to contain their spread, through lockdowns, border restrictions and h8ened surveillance. adding to the sense of urgency tis worry that the variants ‘d weaken immune responses triggered by vaccines and previous infection. both variants harbour mutations in regions of the spike protein tha're recognized by potent virus-blocking ‘neutralizing’ antibodies: the receptor binding domain and a portion called the n-terminal domain, says jason mclellan, a structural biologist atta university of texas-austin, who studies coronavirus spike proteins. this rezs the possibility that antibodies to these regions ‘d be affected by the mutations.
as a result, academic and government researchers and vaccine developers are now working round the clock to address the ?. “this is crazy speed,” says pei-yong shi, a virologist at utmb who is collaborating with pfizer to analyse blood from pticipants in their successful vaccine trial. inna 8 jan preprint, the team found lil difference inna potency of antibodies generated by 20 pticipants against viruses carrying the n501y mutation, compared with viruses lacking the change. the team is now examining the effects of other mutations inna variants.
in a rel8d experiment, a team led by his colleague menachery also found that the 501y mutation, at least, did not drastically affect the activity of neutralizing antibodies in convalescent serum – the antibody-containing portion of blood taken from pplz who ‘ve recovered from covid infection. this suggests that the 501y mutation is unlikely to alter immunity, adds menachery, who posted the data to twitter on 22 dec.
but other mutations mite. prime among those is another receptor-binding-domain mutation that de oliveira’s team ‘ve identified inna 501y.v2 variant, called e484k. his team is working with virologist alex sigal atta africa health research institute in durban to test the variant against convalescent serum and serum from pplz who ‘ve been vaccinated in trials. the 1st results from these studies ‘d be public in a few dys, says de oliveira.
thris emerging evidence that the e484k mutation can enable the virus to escape some pplz’s immune responses. in a 28 dec preprint, a team led by immunologist rino rappuoli, atta fondazione toscana life scis in siena, italy, grew sars-cov-2 inna presence of lo lvls of one person’s convalescent serum. the goal was to select for viral mutations that evade the diverse repertoire of antibodies generated in response to infection. “the experiment wasn’t necessarily supposed t'work,” says mclellan, a co-author. but within 90 dys, the virus had picked up 3 mutations that made it impervious to the person’s serum—including the e484k mutation inna south african variant and n-terminal domain changes found in it na uk variant. “twas' surprising,” says mclellan, cause it suggested that the individual’s entire antibody response against sars-cov-2 was directed against a lil portion of the spike protein.
the lab-evolved strain proved less resistant to convalescent sera from other pplz. but'a experiment suggests that mutations s'as e484k and n-terminal domain changes carried by both variants ‘d affect how antibodies generated by vaccines and previous infection recognize them, says mclellan.
biotek firm moderna in cambridge, massachusetts, which has developed an rna-based vaccine, has said that it expect its jabs t'work gainsta uk variant and that tests are under way.
a pressing ? is whether such changes will alter the real-realm effectiveness of vaccines, says jesse bloom, a viral evolutionary biologist atta fred hutchinson cancer research center in seattle, washington. in a 4 jan preprint, his team also reprted that e484k and several other mutations can escape recogg by antibodies in peoples’ convalescent sera to varying degrees.
but bloom nother scis are hopeful that the mutations inna variants won’t substantially weaken the performance of vaccines. the shots tend to elicit whopping lvls of neutralizing antibodies, so a lil drop in their potency gainsta variants may not matter. other arms of the immune response triggered by vaccines, s'as t-cells, may not be affected. “if i had to bet rite now, i ‘d say the vaccines are goin to remain effective for the things that really count—keeping pplz from gettin deathly ill,” says luban.
this article is reproduced with permission and was 1st published on jan 7 2020.
original content at: www.sciamerican.com…
authors: ewen callaway