Sci­en­tists may have found the key in­gre­di­ent for a univer­sal flu vac­cine – and it comes from lla­mas

The Jerusalem Post - - HEALTH & SCIENCE - • By MELISSA HEALY

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 on­cea-year puff up the nose.

In a study in Fri­day’s edi­tion of the jour­nal Sci­ence, a team from the Scripps Re­search In­sti­tute in La Jolla and their in­ter­na­tional col­leagues have taken a ma­jor step to­ward the long-sought goal of de­vel­op­ing a univer­sal vac­cine against in­fluenza.

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.

Dr. Anthony Fauci, di­rec­tor of the Na­tional In­sti­tute of Al­lergy and In­fec­tious Dis­eases, of­fered a full-throated ap­pre­ci­a­tion for the new study, which re­ceived fund­ing from the Na­tional In­sti­tutes of Health.

“From a sci­en­tific and tech­ni­cal stand­point, this is re­ally a very el­e­gant study – the high­est quality of sci­ence,” Fauci said. He praised it for demon­strat­ing that in or­der to pro­tect peo­ple from pathogens that can change or emerge un­pre­dictably, sci­en­tists must con­struct vac­cines that can knock down an ar­ray of viruses, even in peo­ple whose im­mune sys­tems are frag­ile or com­pro­mised.

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.

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.”

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.

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.

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.

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 ev­ery­one, Fauci said.

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.

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-than-per­ma­nent 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.

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.”

OVER TIME, pa­tients who got the same an­ti­bod­ies re­peat­edly might start to build re­sis­tance to them, he said. Vac­cine mak­ers could counter that by find­ing and in­clud­ing new an­ti­bod­ies in their for­mu­la­tion every few years, he sug­gested.

Ross and other sci­en­tists also cau­tioned that the hu­man im­mune sys­tem might see the llama-de­rived pro­teins as for­eign and at­tack them.

This is not the only univer­sal flu vac­cine un­der de­vel­op­ment. In May, Fauci’s NIAID launched the first clin­i­cal trial to test the safety of a univer­sal flu vac­cine in 120 healthy hu­mans. The can­di­date vac­cine, called M-001, tar­gets por­tions of the flu virus that tend not to change even as other pro­teins do. This should prime the hu­man im­mune sys­tem to rec­og­nize and fight many dif­fer­ent strains of in­fluenza viruses.

Janssen Vac­cines and Preven­tion, a Dutch com­pany that em­ploys some of the study au­thors, has ap­plied for a patent that would cover some of the mol­e­cules de­scribed in the new re­port.

(Los An­ge­les Times/TNS)


SCI­EN­TISTS THINK they have de­vel­oped a univer­sal flu vac­cine from lla­mas – an ar­ray of tiny im­mune sys­tem an­ti­bod­ies.

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