Uğur Şahin, BioNTech CEO (Frank Rumpenhorst/dpa via AP Images)

Will ‘orig­i­nal anti­genic sin’ un­der­mine Omi­cron boost­ers? New re­search sug­gests ‘no’

Mod­er­na and Pfiz­er-BioN­Tech are now rac­ing to de­vel­op Omi­cron-spe­cif­ic boost­ers, hop­ing to be ready if the new im­mune-eva­sive vari­ant be­comes dom­i­nant glob­al­ly. But it wasn’t al­ways clear that vari­ant boost­ers could even work.

Af­ter the first Covid-19 vac­cines were au­tho­rized and talk be­gan of vari­ants and next-gen­er­a­tion vac­cines, sev­er­al vac­ci­nol­o­gists raised con­cerns in the me­dia and the sci­en­tif­ic press about a po­ten­tial­ly dele­te­ri­ous phe­nom­e­non that sounds as if it were born out of the Vat­i­can’s im­munol­o­gy wing: Orig­i­nal anti­genic sin.

OAS — or, as less bib­li­cal­ly in­clined re­searchers like to call it, im­print­ing — was first dis­cov­ered by re­searchers study­ing how old­er peo­ple re­spond to flu vac­cines.

There are about 20 dif­fer­ent flu virus­es. Dif­fer­ent strains are dom­i­nant in dif­fer­ent years and each evolves quick­ly. So every fall, man­u­fac­tur­ers try to in­clude the right virus — and the right ver­sion of each of those virus­es — in the an­nu­al shot, hop­ing to in­duce an­ti­bod­ies that match the virus peo­ple are most like­ly to en­counter.

Re­searchers found, though, that re­gard­less of the vac­cine’s de­sign, peo­ple pro­duced the best and longest-lived an­ti­bod­ies against the flu strains they were first ex­posed to as kids. It was if, like ba­by ducks per­ma­nent­ly mim­ic­k­ing the first duck or hu­man they saw, our im­mune sys­tems per­ma­nent­ly mold­ed around our first in­fec­tion and got stuck there.

Re­searchers feared the same could hap­pen with Covid-19 vac­cines and in­fec­tions. Al­though it’s rel­a­tive­ly straight­for­ward to de­sign an mR­NA vac­cine that codes for a new spike pro­tein, it wasn’t clear whether our im­mune sys­tems would be nim­ble enough to adapt to the new in­struc­tions.

In­ject­ed with a vari­ant-spe­cif­ic boost­er, maybe peo­ple would most­ly just churn out copies of the an­ti­bod­ies they made af­ter their first vac­ci­na­tion or in­fec­tion. That would give the world far less lat­i­tude to re­spond to an im­mune-eva­sive vari­ant like Omi­cron.

Da­ta, though, have since come sug­gest­ing that’s un­like­ly to be a prob­lem with this virus, en­cour­ag­ing vac­cine de­vel­op­ers that they can re­spond should the Omi­cron-spe­cif­ic boost­ers — or boost­ers for a fu­ture vari­ant — be need­ed.

Rather than a fixed im­mune re­sponse to coro­n­avirus­es, re­searchers have ob­served a far more flex­i­ble, tun­able one.

It’s “an im­por­tant sci­en­tif­ic ques­tion,” BioN­Tech CEO Uğur Şahin told re­porters Wednes­day. “And the da­ta that we have ob­served — and again this is pre­lim­i­nary — is en­cour­ag­ing that the im­mune re­sponse can be fine tuned.”

Sahin and oth­er re­searchers’ con­fi­dence come from test runs Mod­er­na and BioN­Tech ran against oth­er vari­ants. Last win­ter, af­ter the first vari­ant that could par­tial­ly evade an­ti­bod­ies from vac­cines, Be­ta, arose in South Africa, Mod­er­na de­signed a new vac­cine con­struct and test­ed it in Phase I.

Al­though Be­ta ul­ti­mate­ly van­ished and Mod­er­na aban­doned the can­di­date, the Phase I study showed that peo­ple giv­en the vari­ant-spe­cif­ic boost­er pro­duced high lev­els of Be­ta-spe­cif­ic an­ti­bod­ies.

“What we’ve seen sug­gests that anti­genic im­print­ing … is not go­ing to be a prob­lem,” said John Mas­co­la, head of the NIH’s vac­cine re­search cen­ter. “I shouldn’t say it’s not go­ing to be a prob­lem, but it hasn’t been a prob­lem so far.”

BioN­Tech has its own, less pub­li­cized stud­ies on vari­ant-spe­cif­ic boost­ers. In Au­gust, the Ger­man biotech launched a 1,245-per­son study to test four types of boost­ers: A boost­er of the orig­i­nal vac­cine; an Al­pha-spe­cif­ic boost­er; a Delta-spe­cif­ic boost­er; and a mul­ti-va­lent boost­er that codes for both the Al­pha spike pro­tein and the Delta spike pro­tein.

Un­re­leased da­ta from those stud­ies, Şahin said, have made the com­pa­ny con­fi­dent they could al­so make a boost­er that com­bines mul­ti­ple vari­ants and con­fers broad­er pro­tec­tion, should that even­tu­al­ly be need­ed.

“One op­tion, which I be­lieve is not very like­ly, could be an Omi­cron-Delta vari­ant,” he said.

Of­fi­cials and ex­ec­u­tives are still track­ing Omi­cron’s spread to see whether spe­cif­ic boost­ers will be need­ed. But if they are, it would be an­oth­er case where the world has man­aged to avoid a po­ten­tial im­muno­log­i­cal bul­let from a virus that, for all the ways it’s sur­prised re­searchers, has proven “stu­pid easy” to vac­ci­nate against.

Ear­ly in the pan­dem­ic, for in­stance, promi­nent im­mu­nol­o­gists and vac­ci­nol­o­gists warned about the risk of an­ti­body-de­pen­dent en­hance­ment, in which the an­ti­bod­ies pro­duced by vac­ci­na­tion or pri­or in­fec­tion ac­tu­al­ly help the virus in­fect more cells. There was ev­i­dence that SARS could do this, but for­tu­nate­ly the vac­cines ul­ti­mate­ly proved to do quite the op­po­site in Covid-19, pow­er­ful­ly sup­press­ing in­fec­tion and dis­ease.

Of course, no one is mak­ing any promis­es yet about Omi­cron boost­ers. Al­though the stud­ies so far point away from orig­i­nal anti­genic sin, they have been com­par­a­tive­ly small and on­ly cov­ered a cou­ple vari­ants.

If Omi­cron boost­ers are need­ed, com­pa­nies will need to run im­muno­log­i­cal stud­ies on the new shots be­fore they’ll be con­fi­dent they work.

“The Phase I tri­al da­ta, and NHP ex­per­i­ments, gen­er­al­ly in­di­cate that the vari­ant-spe­cif­ic boost­ers are not (se­ri­ous­ly) af­fect­ed by OAS. It may be part of the pic­ture, but there does still seem to be ben­e­fit,” John Moore, a vac­ci­nol­o­gist at Weill Cor­nell, said in an email.” Whether that changes re­gard­ing Omi­cron? Slaugh­ter a sheep and in­spect the en­trails … (Make sure you get an­i­mal study ap­provals first of course).”

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.

AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.

De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

Joe Wiley, Amryt Pharma CEO

Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

Sen. Thom Tillis (R-NC) (J. Scott Applewhite/AP Images)

Phar­ma-friend­ly sen­a­tor calls on FDA for a third time to show patent pro­tec­tions should­n't be blamed for high drug prices

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”

Sanofi, GSK tout 72% Omi­cron ef­fi­ca­cy in PhI­II tri­al of next-gen, bi­va­lent shot — with an eye to year-end roll­out

Sometimes, being late can give you an advantage.

That’s what Sanofi and GSK are trying to say as the Big Pharma partners report positive results from a late-stage trial of their next-gen bivalent Covid-19 vaccine, which was designed to protect against both the original strain of the SARS-CoV-2 virus and the Beta variant. Specifically, against Omicron, they note, the vaccine delivered 72% efficacy in all adults and 93.2% in those previously infected.

Rwanda president Paul Kagame and BioNTech CEO Uğur Şahin (via BioNTech)

BioN­Tech breaks ground on first mR­NA vac­cine man­u­fac­tur­ing fa­cil­i­ty in Africa

Covid vaccine access to lower- and middle-income nations has been a concern during the length of the pandemic, but BioNTech is now pushing forward with plans to increase vaccine access for Africa.

Construction work has kicked off for an mRNA manufacturing facility in Kigali, Rwanda. According to BioNTech, the facility, dubbed the African modular mRNA manufacturing facility, has a target for the first set of manufacturing tools to be delivered to the site by the end of this year.