A vac­cine with­out the shot

A pro­to­type of how to fight the next pan­demic

The Prince George Citizen - - Health - Carolyn Y. JOHN­SON

When the next deadly pan­demic flu hits, the first chal­lenge will be to de­velop a vac­cine. But loom­ing be­hind that ob­sta­cle is an­other: how to get an in­oc­u­la­tion to mil­lions of peo­ple with­out in­ad­ver­tently ex­ac­er­bat­ing the cri­sis.

Af­ter all, droves of peo­ple – some per­haps al­ready sick­ened – who flock to health cen­ters for a shot could be a po­tent way for the in­fec­tion to spread.

On the 100th an­niver­sary of the in­fluenza pan­demic of 1918 that sick­ened a third of the world’s pop­u­la­tion and killed 50 mil­lion peo­ple, vac­cine re­searchers are search­ing ur­gently for new ap­proaches to pre­pare for the next pan­demic – a threat most pub­lic health of­fi­cials con­sider in­evitable. A new study pro­vides proof of con­cept for a so­lu­tion that could up­end the tra­di­tional cen­tral­ized model, in which health pro­fes­sion­als give in­jec­tions at clin­ics.

Re­searchers created an H5N1 vac­cine, boosted by a spe­cial in­gre­di­ent that primes the body’s im­mune sys­tem to re­spond. Then they ad­min­is­tered it through a mi­cronee­dle that pen­e­trates only the skin’s up­per layer. They see this pro­to­type tech­nol­ogy as a plat­form that could lead to novel vac­cine patches that can be dis­trib­uted rapidly and ad­min­is­tered with­out a nurse. Peo­ple would sim­ply stick a ban­dage-like strip, lined with mi­cro­scopic nee­dles, onto their skin.

“It’s an ex­cel­lent, ex­tremely com­pre­hen­sive and well-done study,” said Mark Poz­nan­sky, di­rec­tor of the Vac­cine and Im­munother­apy Cen­ter at Mas­sachusetts Gen­eral Hos­pi­tal. He was not in­volved in the re­search, pub­lished in Science Ad­vances. “What they’re sug­gest­ing is some­thing you could stick in an en­ve­lope and get to peo­ple rapidly – it’s an im­por­tant break­through tech­nol­ogy.”

The re­search team com­bined sev­eral dif­fer­ent tech­nolo­gies into their pro­to­type: tiny, hol­low mi­cronee­dles that pen­e­trate only the up­per layer of the skin were paired with vac­cines made from non­in­fec­tious “virus-like par­ti­cles” that can be rapidly pro­duced by tobacco plants. Cru­cially, re­searchers added an­other in­gre­di­ent, called an ad­ju­vant, that speeds up and strength­ens the body’s re­sponse to the vac­cine.

The study, funded by the U.S. De­fense Ad­vanced Re­search Projects Agency, is still at an early stage. Large-scale hu­man tri­als will be needed to de­ter­mine the safety of the ap­proach, which suc­cess­fully pro­tected fer­rets from H5N1 and ap­peared safe in a small hu­man trial to study safety.

Dar­rick Carter, a bio­chemist at the In­fec­tious Disease Re­search In­sti­tute in Seat­tle, said that one of the most ex­cit­ing things their study showed was that the ad­ju­vant seemed to con­fer pro­tec­tion against not just the tar­get virus but also re­lated viruses.

If that ob­ser­va­tion is borne out in fur­ther stud­ies, it could ad­dress an im­por­tant prob­lem in vac­cine development. If the strain of virus used to cre­ate the vac­cine mis­matches the pathogen that is out there cir­cu­lat­ing in the world, the vac­cine be­comes much less ef­fec­tive. The 2016-2017 flu vac­cine, for ex­am­ple, was only mod­er­ately ef­fec­tive be­cause of a mu­ta­tion in the virus.

Be­cause pub­lic health of­fi­cials seek­ing to pre­pare for a pan­demic flu won’t know the ex­act strain in ad­vance and the virus could change dur­ing an out­break, vac­cines that could be made more broadly ef­fec­tive with an ad­ju­vant are ex­cit­ing to re­searchers.

“If you think about the me­chan­ics of how the stock­pile is done, with a sin­gle virus and mil­lions of doses – the prob­a­bil­ity of that ex­act virus emerg­ing is, in my mind, fairly low,” Carter said.

Carter and col­leagues are ea­ger to move the work for­ward but say they have reached some­thing of an im­passe. While they were able to se­cure early fund­ing to demon­strate the science be­hind the tech­nique and show early proof of its clin­i­cal prom­ise, they don’t yet have a part­ner to scale up the ef­fort and test it in a larger pop­u­la­tion.

As they search for sup­port to move the re­search to the next step, they said, they plan to ap­ply the tech­nol­ogy to an area of medicine where fund­ing is typ­i­cally more ac­ces­si­ble: can­cer. They hope that the ad­ju­vant that stim­u­lates the im­mune sys­tem could, if in­jected into a tu­mour, awaken the body’s im­mune cells to at­tack the tu­mour.

What they’re sug­gest­ing is some­thing you could stick in an en­ve­lope and get to peo­ple rapidly – it’s an im­por­tant break­through tech­nol­ogy.

— Mark Poz­nan­sky

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