Covid-19 roundup: South African vari­ant trips up Pfiz­er/BioN­Tech, Mod­er­na vac­cines while EU seeks an­ti-vari­ant con­tract claus­es — re­port

As ques­tions con­tin­ue to swirl about the ef­fec­tive­ness of cur­rent vac­cines against new vari­ants of the coro­n­avirus, a pair of let­ters to the ed­i­tor con­firm that those de­vel­oped by Pfiz­er/BioN­Tech and Mod­er­na ap­pear to be able to pro­tect against the UK vari­ant but less ef­fi­ca­cious when faced with the strain orig­i­nat­ing from South Africa.

Now that the first-gen­er­a­tion vac­cines’ ef­fi­ca­cy against the orig­i­nal SARS-CoV-2 anti­gen has large­ly been es­tab­lished, some sci­en­tists have turned their at­ten­tion to the ques­tions of when, where and how they can be best de­ployed.

The South African vari­ant has al­ready raised glob­al alarms af­ter As­traZeneca’s Ox­ford-part­nered vac­cine was side­lined af­ter it failed a small-scale analy­sis specif­i­cal­ly mea­sur­ing its ef­fi­ca­cy against B.1.351.

Writ­ing to the New Eng­land Jour­nal of Med­i­cine, two dif­fer­ent groups re­port­ed sim­i­lar find­ings about the serum neu­tral­iz­ing ac­tiv­i­ty elicit­ed by the Pfiz­er/BioN­Tech and Mod­er­na shots.

From the let­ter on BNT162b2:

Thus, as com­pared with neu­tral­iza­tion of USA-WA1/2020, neu­tral­iza­tion of Δ242-244+D614G virus was sim­i­lar and neu­tral­iza­tion of the B.1.351-spike virus was weak­er by ap­prox­i­mate­ly two thirds. Our da­ta are al­so con­sis­tent with poor­er neu­tral­iza­tion of the virus with the full set of B.1.351-spike mu­ta­tions than virus with ei­ther sub­set of mu­ta­tions and sug­gest­ed that virus with mu­tant residues in the re­cep­tor-bind­ing site (K417N, E484K, and N501Y) is more poor­ly neu­tral­ized than virus with Δ242-244, which is lo­cat­ed in the N-ter­mi­nal do­main of the spike pro­tein.

Mean­while with mR­NA-1273:

Both the full pan­el of mu­ta­tions in S and a sub­set of mu­ta­tions af­fect­ing the re­cep­tor-bind­ing do­main (RBD) re­gion of the B.1.1.7 vari­ant had no sig­nif­i­cant ef­fect on neu­tral­iza­tion by serum ob­tained from par­tic­i­pants who had re­ceived the mR­NA-1273 vac­cine in the phase 1 tri­al (Fig­ure 1A and 1B). In con­trast, we ob­served a de­crease in titers of neu­tral­iz­ing an­ti­bod­ies against the B.1.351 vari­ant and a sub­set of its mu­ta­tions af­fect­ing the RBD.

In a third let­ter, two Cana­di­an re­searchers sug­gest that the two dos­es of the Pfiz­er/BioN­Tech vac­cine should be giv­en at a longer in­ter­val than cur­rent­ly pre­scribed, based on a new analy­sis on the da­ta both com­pa­nies sub­mit­ted to the FDA.

One dose of the vac­cine, they ar­gue, is ac­tu­al­ly high­er than the 52.4% fig­ure that Phase III in­ves­ti­ga­tors had orig­i­nal­ly thought. If you re­move da­ta from the first two weeks af­ter the first dose, “when im­mu­ni­ty would have still been mount­ing,” the ef­fi­ca­cy would ac­tu­al­ly be much high­er.

“Even be­fore the sec­ond dose, BNT162b2 was high­ly ef­fi­ca­cious, with a vac­cine ef­fi­ca­cy of 92.6%, a find­ing sim­i­lar to the first-dose ef­fi­ca­cy of 92.1% re­port­ed for the mR­NA-1273 vac­cine (Mod­er­na),” they wrote. “Giv­en the cur­rent vac­cine short­age, post­pone­ment of the sec­ond dose is a mat­ter of na­tion­al se­cu­ri­ty that, if ig­nored, will cer­tain­ly re­sult in thou­sands of Covid-19–re­lat­ed hos­pi­tal­iza­tions and deaths this win­ter in the Unit­ed States — hos­pi­tal­iza­tions and deaths that would have been pre­vent­ed with a first dose of vac­cine.” — Am­ber Tong

EU seek­ing an­ti-vari­ant con­tract claus­es — re­port

With the emer­gence of new Covid-19 virus vari­ants and un­cer­tain­ty sur­round­ing vac­cines’ pro­tec­tion against them, the EU is re­port­ed­ly look­ing to en­sure ac­cess to po­ten­tial boost­er shots in its deals with vac­cine mak­ers.

The bloc is adding an­ti-vari­ant claus­es to new vac­cine sup­ply con­tracts and seek­ing to amend its old­er deals, Reuters re­port­ed, with lan­guage that ex­plic­it­ly cov­ers the vari­ants. The ne­go­ti­a­tions come amid the pub­li­ca­tion of stud­ies from Pfiz­er and Mod­er­na that sug­gest low­er an­ti­body lev­els against the South African vari­ant and South Africa it­self halt­ing roll­out of the As­traZeneca/Ox­ford vac­cine af­ter it showed high­ly di­min­ished ef­fi­ca­cy fight­ing the vari­ant in a small tri­al.

Three EU sources con­firmed the news to Reuters, with one of­fi­cial say­ing the claus­es would al­low the bloc to fo­cus on buy­ing up­grad­ed shots rather than vac­cines that are not ef­fec­tive against the wide­spread vari­ants. How­ev­er, the source added the de­f­i­n­i­tion of “vari­ant” in the new con­tracts re­mained vague, and it was un­clear what le­gal pow­er the con­tracts would give the EU.

All three con­firmed that one of these claus­es was in­clud­ed in the new EU con­tract with Pfiz­er and BioN­Tech signed ear­li­er this month. The deal is ex­pect­ed to sup­ply 300 mil­lion ad­di­tion­al dos­es of the pair’s mR­NA vac­cine.

In to­tal, the EU has se­cured deals to ac­quire rough­ly 2.6 bil­lion vac­cines from six com­pa­nies, and is still ne­go­ti­at­ing with No­vavax, Val­ne­va and Mod­er­na to pur­chase even more.

On Wednes­day af­ter­noon, Pfiz­er and Mod­er­na pub­lished re­search in the New Eng­land Jour­nal of Med­i­cine say­ing their vac­cines still of­fer enough pro­tec­tion to neu­tral­ize the South African vari­ant, but pro­duce sig­nif­i­cant­ly few­er an­ti­bod­ies in re­sponse. The study was con­duct­ed in a lab­o­ra­to­ry set­ting and it re­mains un­clear whether the same re­sponse would be seen in re­al life. — Max Gel­man

Mex­i­co fac­to­ry pro­duc­ing As­traZeneca shot al­most ful­ly up­grad­ed

Mex­i­co had been prepar­ing to pack­age and dis­trib­ute the As­traZeneca/Ox­ford vac­cine through­out Cen­tral Amer­i­ca, but that process had been held up by nec­es­sary fac­to­ry changes. Now, the coun­try is al­most ready to start.

The fac­to­ry up­grade had been held up by a se­ries of com­plex cer­ti­fi­ca­tion process­es af­ter health reg­u­la­tors could not de­ter­mine whether the plant could safe­ly pro­duce Covid-19 shots, Reuters re­port­ed. On an in­spec­tion vis­it to the fac­to­ry, which pre­vi­ous­ly made flu shots, of­fi­cials not­ed 185 “ob­ser­va­tions” that need­ed to be fixed.

“They al­most had to make an­oth­er fac­to­ry,” Mex­i­can for­eign min­is­ter Marce­lo Ebrard said at a gov­ern­ment news con­fer­ence, per Reuters. “You are talk­ing about health, life … so you do have to be very strict in any med­i­cine, with a vac­cine more, and even more when the vac­cine is so re­cent.”

Mex­i­co had re­ceived at least two ship­ments of As­traZeneca’s ac­tive vac­cine in­gre­di­ent but had not fin­ished pro­duc­ing dos­es of the shot. The fac­to­ry is now ex­pect­ed to start ship­ping the dos­es by ear­ly April, Ebrard said.

With the back­ing of Mex­i­can bil­lion­aire Car­los Slim, As­traZeneca had reached agree­ments with Mex­i­co and Ar­genti­na to dis­trib­ute their shots through­out the Cen­tral and South Amer­i­can re­gions. Mex­i­co al­so is aim­ing to speed up its vac­cine cam­paign, hav­ing im­port­ed 870,000 As­traZeneca shots from In­dia on Sun­day. — Max Gel­man

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

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