The key in­gre­dient for a uni­ver­sal flu vac­cine

Le vac­cin uni­ver­sel contre la grippe, bien­tôt une réa­li­té ?

Vocable (Anglais) - - Édito | Sommaire -

Chaque an­née, la grippe touche sé­vè­re­ment des mil­lions de per­sonnes dans le monde. Les vi­rus grip­paux étant très chan­geants d’an­née en an­née, la com­po­si­tion des vac­cins contre la grippe est éga­le­ment mo­di­fiée chaque an­née. Les scien­ti­fiques n’ont pour l’ins­tant pas réus­si à mettre au point un vac­cin « uni­ver­sel » qui se­rait ef­fi­cace dans la du­rée et contre un maxi­mum de souches. Mais ce­la est peut-être sur le point de chan­ger...

Along with soul­ful eyes, en­dea­rin­gly long necks and warm fuz­zy coats, lla­mas have a far less ap­pre­cia­ted fea­ture: They make an ar­ray of im­mune sys­tem an­ti­bo­dies so ti­ny they can fit in­to cre­vices on the sur­face

of an in­va­ding vi­rus. That feat could one day pro­tect hu­mans from en­tire fa­mi­lies of flu vi­ruses that be­de­vil scien­tists with their un­pre­dic­table and shape-shif­ting ways. All, po­ten­tial­ly, with a once-a-year puff up the nose.

2. In a stu­dy pu­bli­shed in the jour­nal Science, a team from the Scripps Re­search Ins­ti­tute in La Jol­la and their in­ter­na­tio­nal col­leagues have ta­ken a ma­jor step to­ward the long­sought goal of de­ve­lo­ping a uni­ver­sal vac­cine against in­fluen­za.

3. When they tes­ted their in­tra­na­sal for­mu­la­tion in mice, it qui­ck­ly confer­red com­plete

pro­tec­tion against a raft of hu­man flu strains adap­ted to mice. Those in­clude A vi­ruses, such as the H1N1 “swine flu” that tou­ched off a glo­bal pan­de­mic in 2009, and B vi­ruses, which oc­cur on­ly in hu­mans. Against H1N1, a dose of the ex­pe­ri­men­tal vac­cine was shown to pro­tect for at least 35 days — a span of time equi­va­lent to more than a single flu sea­son for hu­mans.

LLA­MAS’ AN­TI­BO­DIES

4. In­fluen­za is a vi­ral scourge that kills as ma­ny as 650,000 people each year, ac­cor­ding to the World Health Or­ga­ni­za­tion. To fight it, the re­search team bor­ro­wed new tech­niques from im­mu­no­lo­gy, mi­cro­bio­lo­gy, na­no­tech­no­lo­gy and ge­ne­tic en­gi­nee­ring labs

around the world. First, they vac­ci­na­ted lla­mas against a num­ber of A and B strains of in­fluen­za. Then they took blood samples to col­lect the an­ti­bo­dies the lla­mas pro­du­ced in res­ponse.

5. Among them were four uni­que­ly small an­ti­bo­dies that sho­wed an abi­li­ty to des­troy ma­ny dif­ferent strains of in­fluen­za. In a nod to their size and func­tion, they cal­led their crea­tions “na­no­bo­dies.”

6. From those mul­ti­tas­king lit­tle po­we­rhouses, the re­sear­chers en­gi­nee­red a single pro­tein ca­pable of squee­zing in­to spaces on a vi­rus’ sur­face that are too small for most pro­teins. The re­sul­ting “mul­ti­do­main an­ti­bo­dy MD3606,” with its “im­pres­sive breadth and po­ten­cy,” could confer pro­tec­tion against pret­ty much any strain of flu that na­ture could throw in hu­man­kind’s way, the stu­dy au­thors said. 7. If the do­mi­nant strain in a gi­ven sea­son were to sud­den­ly change, these an­ti­bo­dies would be rea­dy for the un­wel­come guest. If a flu strain came out of now­here and threa­te­ned a po­pu­la­tion with no im­mu­ni­ty to it — the night­mare sce­na­rio of pan­de­mic flu — this su­per­char­ged de­fen­der would re­co­gnize that flu and coun­ter it. If health of­fi­cials gues­sed wrong about what flu strain was co­ming and or­de­red up a vac­cine that would be lar­ge­ly in­ef­fec­tive — a sce­na­rio that played out last flu sea­son — this pa­ckage of an­ti­bo­dies could save the day.

VI­RAL DELIVERY DEVICE

8. But the re­sear­chers still fa­ced a key hurdle: get­ting the hu­man im­mune sys­tem to make such a su­per-pro­tein even when it’s wei­ghed down by age, stress and di­sease. Their so­lu­tion: Don’t even try. Ins­tead, they de­vi­sed a way to work around hu­mans’ un­re­liable res­ponse to vac­cines, buil­ding a gene that en­co­ded the pro­duc­tion plans for their po­we­rhouse pro­tein. To fer­ry that gene in­to a host or­ga­nism, they en­lis­ted a harm­less vi­rus used by labs wor­king on gene the­ra­py.

9. By spli­cing their de­si­gner gene in­to this vi­ral delivery device, the scien­tists not on­ly found a way to get their an­ti­bo­dy pa­ckage in­to a host, they were de­li­ve­ring the ma­nu­fac­tu­ring ma­chi­ne­ry to pro­duce it. This “pas­sive trans­fer” of an­ti­bo­dies gives this vac­cine can­di­date the po­ten­tial to be equal­ly ef­fec­tive in eve­ry- one, Dr. An­tho­ny Fau­ci, di­rec­tor of the Na­tio­nal Ins­ti­tute of Al­ler­gy and In­fec­tious Di­seases, said.

YEARLY FLU VAC­CINE

10. The next step is to conduct fur­ther tests in ani­mals and cli­ni­cal trials in hu­mans, and that “will take years,” he said. “But if ful­ly suc­cess­ful — a ma­jes­tic leap right now — it could es­sen­tial­ly eli­mi­nate the need from sea­son to sea­son” to di­vine which of count­less pos­sible flu vi­ruses will rear up, and to then build a yearly flu vac­cine that neat­ly fits the bill.

11. Scripps im­mu­no­lo­gist Ian Wil­son, the stu­dy’s se­nior au­thor, said that as the cells “in­fec­ted” by the delivery vi­rus turn over, repeated doses might be nee­ded to sus­tain the pro­duc­tion of an­ti­bo­dies. “We don’t real­ly know how long this treat­ment would sur­vive in hu­mans yet,” he said. But even less-than­per­ma­nent im­mu­ni­ty against a broad range of flu threats would help buf­fer people from the emer­gence of unex­pec­ted flu strains, Wil­son said. And the ra­pid res­ponse of mice to the vac­cine sug­gests it could be used to ino­cu­late a po­pu­la­tion af­ter a new vi­ral threat has emer­ged, he ad­ded.

12. That the ex­pe­ri­men­tal vac­cine might need to be ad­mi­nis­te­red each year makes it an in­ter­es­ting hy­brid, said Ted M. Ross, who di­rects the Uni­ver­si­ty of Geor­gia’s Cen­ter for Vac­cines and Im­mu­no­lo­gy. “This ap­proach is si­mi­lar to an­ti­ve­nom,” said Ross. “The the­ra­peu­tic is an an­ti­bo­dy that was made in ano­ther spe­cies to neu­tra­lize the toxin. It’s short-term, but it gets you through the per­iod of time where bad things could hap­pen.”

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