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A prototype of how to fight the next pandemic: A vaccine without the shot

In this 1918 photo, volunteer nurses from the American Red Cross tend to influenza patients in the Oakland Municipal Auditorium, used as a temporary hospital. Vaccine researchers are racing to develop new technologies to avoid a repeat of the pandemic, which killed 50 million people. (Edward A. "Doc" Rogers/Library of Congress/AP)

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 who might already be 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 ur­gent­ly search­ing for new ap­proach­es to pre­pare for the next pan­dem­ic — a threat that 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 only pen­et­rates the up­per lay­er of the skin. 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 have to 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, who was not in­volved in the re­search, which was 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."

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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 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 not just against the tar­get vi­rus but also to 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 was only mod­er­ate­ly ef­fec­tive, for ex­am­ple, 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 try 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 tu­mor, a­wak­en the body's im­mune cells to attack the tu­mor.

Read More:

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HPV-re­lated can­cer rates are ris­ing. So are vac­cine rates — just not fast en­ough.