Anthony Fauci, NIAID director (AP Images)

As new Covid-19 task force gets un­der­way, threat looms of vac­cine, mon­o­clon­al an­ti­body-re­sis­tant vari­ants

Hours be­fore Pres­i­dent Biden’s Covid-19 team gave their first vir­tu­al press con­fer­ence, the famed AIDS re­searcher David Ho de­liv­ered con­cern­ing news in a new pre-print: SARS-CoV-2 B.1.351, the vari­ant that emerged in South Africa, is “marked­ly more re­sis­tant” to an­ti­bod­ies from con­va­les­cent plas­ma and vac­ci­nat­ed in­di­vid­u­als.

The news for sev­er­al mon­o­clon­al an­ti­bod­ies, in­clud­ing Eli Lil­ly’s bam­lanivimab, was even worse: Their abil­i­ty to neu­tral­ize was “com­plete­ly or marked­ly abol­ished,” Ho wrote. Lil­ly’s an­ti­body cock­tail, which was just shown to dra­mat­i­cal­ly re­duce the risk of hos­pi­tal­iza­tions or death, al­so be­came far less po­tent.

The B1.351 vari­ant has yet to be seen in the US, new CDC di­rec­tor Rochelle Walen­sky as­sured re­porters, but the vari­ants nonethe­less took up a sub­stan­tial por­tion of the first Covid-19 brief­ing, as Walen­sky and NI­AID di­rec­tor An­tho­ny Fau­ci out­lined steps the US would take as they be­came more com­mon in the coun­try and as the virus con­tin­ues to mu­tate, po­ten­tial­ly in ways that make them yet more re­sis­tant to vac­cines and an­ti­bod­ies.

The B.1.1.7 vari­ant, now dom­i­nant in the UK and grow­ing in the US, hasn’t been able to sig­nif­i­cant­ly elide vac­cines or mon­o­clon­al an­ti­bod­ies, Fau­ci said. There’s grow­ing ev­i­dence, though, that the vari­ant com­mon in South Africa can avoid mon­o­clon­als and some an­ti­bod­ies pro­duced by vac­cines.

Be­cause the Pfiz­er and Mod­er­na vac­cines are so ef­fec­tive, Fau­ci said, po­ten­cy can drop con­sid­er­ably with­out im­pact­ing ef­fi­ca­cy, and there are no da­ta to sug­gest the vac­cine isn’t still pro­tec­tive.

“How­ev­er,” he said, “giv­en that as a fact now, we have to be con­cerned about what fur­ther evo­lu­tion of this might be.”

So far, the on­ly tests for whether vac­cines and mon­o­clon­al an­ti­bod­ies can neu­tral­ize new vari­ants have been in vit­ro stud­ies — test tube ex­per­i­ments where the an­ti­bod­ies are mixed with a fake ver­sion of SARS-CoV-2 the ex­per­i­menter checks to see whether the virus still man­aged to in­fect cells. Those ex­per­i­ments, con­duct­ed both by com­pa­nies and in aca­d­e­m­ic labs, have been en­cour­ag­ing for B.1.1.7 and dis­cour­ag­ing for B.1.351.

The new Ho pa­per, for ex­am­ple, con­duct­ed in col­lab­o­ra­tion with the NIH and Re­gen­eron, showed 10 out of 12 an­ti­bod­ies were equal­ly ef­fec­tive against B.1.1.7 and two were on­ly slight­ly less ef­fec­tive, while vac­cine ef­fi­ca­cy fell 2-fold. The B.1.351 vari­ant, though, al­most en­tire­ly avoid­ed five of the mon­o­clon­al an­ti­bod­ies, while vac­cine ef­fi­ca­cy fell 6.5-fold for Pfiz­er and 8.6-fold for Mod­er­na.

Soon, though, the US is like­ly to get da­ta on how the vac­cine works against the dif­fer­ent vari­ants in the re­al world, Fau­ci said. J&J con­duct­ed their piv­otal vac­cine tri­al around the world, in­clud­ing in South Africa and Brazil, where an­oth­er vari­ant, called P.1, has spread. Their re­sults should come “with­in the next few days,” Fau­ci said.

“What we will see was the rel­a­tive ef­fi­ca­cy against the wild type virus that is pre­dom­i­nant­ly in the US, as well as the South African iso­late,” Fau­ci said. It “will in­form us of where we would go, if the even­tu­a­tion oc­curs that we do have that par­tic­u­lar lin­eage seed it­self in the Unit­ed States.”

In the mean­time, vac­cine and an­ti­body de­vel­op­ers have been prepar­ing for that po­ten­tial. Mod­er­na de­vel­oped a vac­cine de­signed specif­i­cal­ly for B.1.351 and has said they will start Phase I tri­als us­ing both the new vac­cine and the orig­i­nal as a boost­er shot. Pfiz­er and No­vavax said they are al­so draw­ing up con­tin­gency plans.

The Ho pa­per point­ed an­ti­body de­vel­op­ers, who are more acute­ly threat­ened by a mu­tat­ing virus than vac­cine com­pa­nies, to a po­ten­tial so­lu­tion. Al­though Eli Lil­ly’s main an­ti­body did lit­tle against the new vari­ant, Re­gen­eron’s com­bo still suc­cess­ful­ly neu­tral­ized it, point­ing to the po­ten­tial im­por­tance of com­bi­na­tion strate­gies.

Still, a com­bo isn’t nec­es­sar­i­ly a panacea, as shown by the low po­ten­cy Ho found for Lil­ly’s cock­tail. The In­di­anapo­lis-based Big Phar­ma an­nounced this morn­ing, though, that they be­gan ex­per­i­men­tal­ly dos­ing pa­tients with a com­bi­na­tion of bam­lanivimab and an an­ti­body Vir and GSK are co-de­vel­op­ing. In a state­ment, GSK not­ed that the two an­ti­bod­ies bind to dif­fer­ent epi­topes, or sub-units, of the virus.

Vir could al­so emerge as a win­ner in the hunt for an ef­fec­tive sin­gle an­ti­body. Re­ly­ing on an an­ti­body that al­so neu­tral­izes the orig­i­nal SARS virus, they long po­si­tioned them­selves as de­vel­op­ing the best an­ti­body should the virus mu­tate. Al­though their po­ten­cy was re­duced against B.1.351, it still ef­fec­tive­ly neu­tral­ized the vari­ant. A large tri­al of the an­ti­body is due to read out in the com­ing weeks.

Re­spond­ing to the new strains, how­ev­er, will re­quire the US to prop­er­ly mon­i­tor the genomes of virus­es en­ter­ing the coun­try and to track how the virus evolves with­in the coun­try. So far, the US has lagged con­sid­er­ably in se­quenc­ing virus­es, of­fi­cials ac­knowl­edged at the brief­ing, rank­ing 43rd in the world ac­cord­ing to one count.

The new health of­fi­cials promised that would im­prove, not­ing that Biden’s new stim­u­lus and re­lief bill in­cludes funds for ge­nom­ic sur­veil­lance.

“It is es­sen­tial as part of the Amer­i­can res­cue plan,” said Jef­frey Zients, co­or­di­na­tor of Biden’s Covid-19 re­sponse.

Fau­ci added that se­quenc­ing will be sup­ple­ment­ed with con­tin­u­al stud­ies to test whether an­ti­bod­ies from vac­cines neu­tral­ize new vari­ants and when it’s time to push for­ward mod­i­fied vac­cines or an­ti­bod­ies.

“All of that is go­ing on,” he said, “lit­er­al­ly as we speak.”

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