Fast-Spreading Covid Variant Can Elude Immune Responses

News in focus a risk to countries outside where it originated But governments around the world ignored The WHO therefore relies on diplomacy, and if it requires an international response — those calls. For example, the United States did which often boils down to praising or shaming meaning, in some cases, that it could have not roll out testing across the country until countries. But the WHO’s appetite for criticism pandemic potential. late February, and it banned some travel from is limited by its reliance on donations from its With each PHEIC, the WHO advises govern- China, where the virus was first discovered. member countries and on countries openly ments on how to deal with the emergency. For Countries seem to agree that to improve the offering access and information — which could example, last January, WHO director-general world’s ability to respond to pandemics, the be withheld if leaders felt insulted. A case in Tedros Adhanom Ghebreyesus said of the WHO should be transformed and bolstered. point is that the WHO spent weeks gently COVID-19 outbreak, “It is still possible to Speaking as a representative of the United persuading China to permit an international interrupt virus spread, provided that countries States, Anthony Fauci, director of the US team of scientists to visit Wuhan after the out- put in place strong measures to detect disease National Institute of Allergy and Infectious break was reported there. On the financing early, isolate and treat cases, trace contacts Diseases, told the WHO on 21 January that the front, researchers say that a larger, reliable and promote social-distancing measures.” country will reverse its withdrawal from the budget for the WHO would give the organization greater autonomy because it wouldn’t What’s in a name? “The real question is, what be dependent on fundraising amid a disaster. Liu admits that the term PHEIC isn’t as sexy To address communication concerns, Tedros as an emotive word, such as ‘pandemic’ or would it take for people has suggested adding a gradient of warnings to ‘emergency’. But researchers and health offi- to do something when a the PHEIC, coded by colour. The colours could cials chose it partly because they wanted to declaration happens?” separate emergencies that might evolve into a avoid panic while encouraging world leaders pandemic from those that are serious but won’t to act according to WHO advice, says Gian affect nations across the globe. Countries with Luca Burci, an international law specialist at organization, initiated by former president outbreaks might more willingly share informa- the Graduate Institute of International and Donald Trump, and will “work constructively tion if there were a low-grade alarm that was Development Studies in Geneva, Switzerland. with partners to strengthen and importantly less likely to result in disruptions to people’s Burci helped to revise the regulations in 2005. reform the WHO”. livelihoods or the economy. In hindsight, that reasoning seems to be One change to strengthen the WHO could be Reforms won’t come until the World Health flawed. Several reports note that politicians a new treaty on pandemics, proposed by the Assembly in May — at the earliest. The possi- and the public mainly ignored the PHEIC decla- president of the European Council, Charles bility of solutions being delayed or forgotten ration and Tedros’s corresponding recommen- Michel. On 20 January, Tedros said he would fills Liu with dread, because she recalls dozens dations in January 2020, but started listening assemble a working group to explore this p. of panels assessing failures in the response to when the organization used the unofficial term Still, the WHO probably wouldn’t have the the Ebola outbreak in West Africa in 2014–16. ‘pandemic’ to describe COVID-19 in March, ability to penalize countries that don’t com- “Less than 10% of the recommendations were once the disease was spreading on multiple ply with the treaty. “There’s no silver bullet followed up on,” she says. “We have an amazing continents. Unlike the PHEIC, ‘pandemic’ is not here since you’re dealing with a community talent to outrage ourselves about a situation, a defined declaration, and countries haven’t of nations, all of whom guard their sovereignty but when it comes time to deliver any change, agreed to take any actions once it’s used. very closely,” says Steven Solomon, principal there is very little traction, and people go back Despite the disproportionate response to legal officer at the WHO. to doing whatever they had done before.” the word pandemic, many scholars argue that changing the name of the WHO’s highest alarm wouldn’t be useful. “I don’t care for the term PHEIC,” says Alexandra Phelan, a global-health lawyer at Georgetown University in Washing- ton DC, “but I worry that if we get too into the FAST-SPREADING COVID words, we miss the point that countries need to act appropriately when there is a declaration.” VARIANT CAN ELUDE Global-health scholars question why a PHEIC for COVID-19 wasn’t declared sooner. On 22 IMMUNE RESPONSES January 2020, Tedros convened a closed-door meeting of virologists, public-health research- Early studies find that a variant of the virus identified ers and certain government representatives — as the PHEIC process dictates. They decided in South Africa could compromise immunity. that a warning wasn’t warranted, but a week later, the committee flipped its position. The By Ewen Callaway some of the results could portend a reduction delay might have cost the world time to con- in the effectiveness of COVID-19 vaccines. tain the virus. vidence is growing that some corona- But the picture is murky, Altmann and Still, a one-week lag in declaring a global virus variants could evade immune other scientists emphasize. The studies — emergency isn’t even the most concerning responses triggered by vaccines and which examined the blood of small numbers action that took place in the early days of the previous infections. Researchers are of people who had recovered from COVID‑19 COVID-19 pandemic, critics say. When Tedros trying to make sense of a tsunami of or received a vaccine — probed only their declared the PHEIC, he advised governments Elaboratory studies released last week that raise antibodies’ capacity to ‘neutralize’ variants to move fast with public-health measures concerns about some emerging variants and in laboratory tests, and not the wider effects of including tests and social distancing. He also mutations. other components of their immune response. asked them to resist bans on travel and trade “Some of the data I’ve seen have really scared Neither do the studies indicate whether because, historically, they had been of limited me,” says Daniel Altmann, an immunologist the changes in antibody activity make any utility and are potentially harmful. at Imperial College London, who worries that difference to the real-world effectiveness of

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A l l r i g h t s r e s e r v e d . to thevast majority of people’s sera. of 44participants, andwere partly resistant resistant to convalescent serum from 21 out full package of 501Y.V2 mutationswere fully N-terminal domains. Pseudoviruses with the key regions of spike: itsreceptor-binding and neutralizing antibodiesthatrecognize two contains mutationsthatblunttheeffects of CoV-2 spike protein. form of HIVthatinfects cells usingtheSARS- did this using a‘pseudo mutations foundin501Y.V2. Theresearchers serum onvarious combinations of spike Africa, probed the effects of convalescent of theWitwatersrand inJohannesburg, South Communicable Diseases and the University Penny Moore attheNationalInstitute for Oliveira. “It’s extremely worrying.” power was substantially weakened, says de from others,butinallcases, theneutralizing formed better against 501Y.V2 thandidplasma people’sin thepandemic. Some plasmaper at neutralizing variants thatcirculated earlier was muchworse atneutralizing 501Y.V2 than researchers foundthattheconvalescent serum antibodies thatcanprevent infection. The to contain neutralizing, orvirus-blocking, of thevirus.Thisconvalescent serum tends ered from COVID-19 caused by otherversions blood — taken from six people who had recov serum of —theantibody-containing portion They thentested thevariant samplesagainst viruses from peopleinfected withthevariant Durban andothercolleagues isolated 501Y.V2 Sigal attheAfricaHealthResearch Institute in previously established immuneresponses. could explained bepartly by itsabilityto elude wondered whetherthe rapid spread of 501Y.V2 Africa’s COVID-19 first wave, andresearchers againstactivity thevirus. some changes linked to weakened antibody andinfectto identify host cells —including system’s primetarget, whichallows thevirus in theSARS-CoV-2 spike protein —theimmune countries since spread across Africaandinto other South epidemic in Eastern Capeprovince that has the variant —called501Y.V2 —to afast-growing KwaZulu-Natal in Durban, Africa, linked South a bioinformaticianattheUniversity of late 2020. Ateam ledby Tulio deOliveira, that researchers Africa in in South identified Much of the concern centres around a variant onimmunity Impacts who co-ledoneof thestudies. the Rockefeller University inNewYork City, don’t know,” says Paul Bieniasz, avirologist at these changes going Ireally to beimportant? vaccines or the likelihood of reinfection. “Are Both South African teamsBoth South will soon test These experiments showed that 501Y.V2 In a separate study To investigate this, de Oliveira, virologist Alex The Eastern Capewas hithard by South 1 . Thelineage carriesmany mutations 3 , a team led by virologist virus’ —amodified 2 - - . become apipedream.” herd would immunity whole ideaof “The mRNA vaccines who hadreceived orModerna eitherthePfizer drop inthepotency of antibodiesfrom people ing domainof 501Y.V2 caused onlyamodest found that mutations in the receptor-bind labs worldwide. A team co-led by Bieniasz trials, andsimilarstudies are underway at ple whoparticipated inCOVID-19 vaccine A coronavirus centre testing inSouthAfrica, where the501Y.V2 variant was detectedin2020. ize theinfection.” to Itcanalsobedifficult son still hasenoughantibodies to neutral have aneffect inapersonbecause thatper some change inalabassay, whichdoesnot in Rotterdam, theNetherlands.“You cansee a virologist attheErasmus MedicalCentre problem inpractice, says Marion Koopmans, such as501Y.V2 mightnotbemuchof a experimental studies needto bedone.” variants should be covered,” Thiel says. “But response thatisdiverse enoughthatthese new gene, they should still mount an immune “Although the vaccines target only the spike such as Tcells, might not beaffected by 501Y.V2. other components of theimmuneresponse, are likely to beable to blockviral variants. And of thespike protein, sosomeof themolecules levels of antibodiesthattarget diverse regions Switzerland. Most COVID-19 vaccines elicithigh an RNAvirologist attheUniversity of Bernin of vaccines isstillsays uncertain, Volker Thiel, consequences of othermutationsin501Y.V2. says Moore, to test butitwillbeimportant the the 501Y.V2 variant with serum from peo Whether these could lessen theeffectiveness A dampenedantibodyresponse to variants ©

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A l l r i g h t s r e s e r v e d . - - - - waning immuneresponses from infec thefirst - disentangle whether reinfections are due to 6. 5. 4. 3. 2. 1. a pipedream, atleast from natural infection”. whole ideaof herd immunitywould become reinfections. Ifthey are, says deOliveira, “the mutations in501Y.V2 are responsible for ority forresearchers to determine whether the pandemic are notyet clear. Itisatop pri they could asantibodylevels wane over time. vaccine’s effectiveness now, says Gupta,but changes shouldn’t make adifference to the against otherversions of SARS-CoV-2. These ple’s sera was less effective against B.1.1.7 than immunization received of two thefirst doses of thesame looked atthesera peoplewhohad of 15 Gupta attheUniversity of Cambridge, UK, vaccine thecompany developed withPfizer on sera from 16 peoplewhohadreceived the that B.1.1.7’s spike mutations had little effect tech BioNTech firm inMainz,Germany, found pseudovirus experiments, researchers atbio intheUnited Kingdom,fied known asB.1.1.7. In behaviour of afast-spreading variant identi Clues are alsobeginningto emerge aboutthe Emerging data tion, orto theeffects of amutation,sheadds. Meanwhile, a team led by virologist Ravindra What last week’s results mean for battling org/10.1101/2021.01.19.21249840 (2021). Collier, D. A. org/10.1101/2021.01.18.426984 (2021). et al. PreprintMuik, A. at bioRxiv https://doi. org/10.1101/2021.01.15.426911 (2021). Wang, Z. org/10.1101/2021.01.18.427166 (2021). Wibmer, C. W. Sigal.pdf (2021). wp-content/uploads/2021/01/MEDRXIV-2021-250224v1- Cele, S. org/10.1101/2020.12.21.20248640 (2020). Tegally, H. Nature |Vol 589 | 28 January 2021 |501 et al. Preprint at https://www.ahri.org/ et al. Preprint at bioRxiv https://doi. et al. Preprint at medRxiv https://doi. et al. Preprint at medRxiv https://doi. et al. Preprint at bioRxiv https://doi. 6 ; theteam foundthat10 peo 5 - - - - .

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