Not cowed by HIV

In the strug­gle against HIV, sci­en­tists get help from cows.

The Star Malaysia - Star2 - - Science - By BRADLEY J. FIKES

PROSPECTS for de­feat­ing HIV, once con­sid­ered an in­vin­ci­ble killer, look brighter with ma­jor ad­vances against the AIDS-caus­ing virus dis­cussed at an in­ter­na­tional con­fer­ence last week.

One of those pieces of good news comes from The Scripps Re­search In­sti­tute in La Jolla. In col­lab­o­ra­tion with the In­ter­na­tional AIDS Vac­cine Ini­tia­tive, its re­searchers have gen­er­ated “broadly neu­tral­is­ing an­ti­bod­ies” that kill HIV us­ing an un­ex­pected source – cows.

The star­tling feat was an­nounced in a study pub­lished in the jour­nal Na­ture. It marks an­other mile­stone toward the long-elu­sive aim of cre­at­ing a vac­cine against the virus, with the an­ti­bod­ies per­haps also lead­ing to cre­ation of new HIV drugs.

“It takes hu­mans years” for the im­mune sys­tem to trig­ger for­ma­tion and full pro­duc­tion of broadly neu­tral­is­ing an­ti­bod­ies. “The cows solved it in a cou­ple of months,” said Den­nis Bur­ton, co-au­thor of the new re­port and a long-time re­searcher of such an­ti­bod­ies at Scripps Re­search.

In other news at the 9th IAS Con­fer­ence on HIV Science in Paris, re­searchers high­lighted the case of an HIV-in­fected child who has ap­par­ently been cured of the virus. They also an­nounced suc­cess in us­ing a long-last­ing in­jec­tion to sup­press HIV lev­els.

Yet an­other study showed that cer­tain HIV drugs were able to pre­vent trans­mis­sion of the virus in hun­dreds of cou­ples where at least one per­son was HIV-pos­i­tive.

De­spite the progress, HIV con­tin­ues to spread and de­stroy lives, said Mark Fein­berg, the vac­cine ini­tia­tive’s pres­i­dent and CEO.

“To me, the most sig­nif­i­cant thing is how the epi­demic con­tin­ues to rav­age many coun­tries and com­mu­ni­ties, and is still such a ma­jor threat to so many peo­ple’s lives,” Fein­berg said.

“While this dis­ease may have re­ceded from the head­lines, it hasn’t gone away. And un­less things are really stepped up, it’s go­ing to get worse rather than bet­ter. That is part of the dis­cus­sion tak­ing place in Paris.”

In the United States, 1.2 mil­lion peo­ple are liv­ing with HIV. The world­wide num­ber is 37 mil­lion, with many of the pa­tients liv­ing in poor coun­tries with in­ad­e­quate health­care.

Mostly in Sub-Sa­ha­ran Africa, peo­ple can’t get ready ac­cess to the drugs that have turned HIV from a vir­tual death sen­tence when it was dis­cov­ered in the 1980s into to­day’s man­age­able dis­ease.

And a lack of aware­ness of how the virus is trans­mit­ted means more are in­fected all the time.

About 2.1 mil­lion new in­fec­tions oc­curred world­wide in 2015, ac­cord­ing to the US Na­tional In­sti­tute for Al­lergy and In­fec­tious Dis­eases.

Over the course of the HIV-AIDS epi­demic, more than 70 mil­lion peo­ple have been in­fected with HIV, ac­cord­ing to the World Health Or­ga­ni­za­tion. About 35 mil­lion of them have died of ac­quired im­mun­od­e­fi­ciency syn­drome

Dur­ing this time, nu­mer­ous ef­forts have been launched to de­velop a vac­cine against HIV. But none of those projects has demon­strated more than a mod­est ben­e­fit in re­duc­ing the rate of in­fec­tion.

Broadly neu­tral­is­ing an­ti­bod­ies have long been re­searched in­ten­sively for clues on mak­ing a bet­ter HIV vac­cine. It’s hard for the hu­man im­mune sys­tem to pro­duce th­ese an­ti­bod­ies be­cause HIV mu­tates pro­lif­i­cally, pre­sent­ing a mov­ing tar­get.

When th­ese an­ti­bod­ies fi­nally ar­rive, the virus is too well-es­tab­lished to erad­i­cate from the pa­tient’s body, said Dr An­thony Fauci, direc­tor of the Na­tional In­sti­tute of Al­lergy and In­fec­tious Dis­eases.

But if the im­mune sys­tem could be trained with a vac­cine to make th­ese pow­er­ful an­ti­bod­ies be­fore any in­fec­tion oc­curs, the virus might be blocked from get­ting a foothold, Fauci said.

In the study from Scripps Re­search and the vac­cine ini­tia­tive, calves were in­jected with HIV frag­ments se­lected to pro­voke pro­duc­tion of broadly neu­tral­is­ing an­ti­bod­ies. Their quick re­sponse was re­mark­able, said Bur­ton and study co-au­thor Vaughn Smider, a Scripps Re­search col­league.

It’s thought that the bovine im­mune sys­tem’s pow­ers pro­tect it from ex­ten­sive ex­po­sure to mi­crobes in its gut as it chews and rechews its cud.

This power may be con­ferred by a pe­cu­liar­ity of cows’ an­ti­body struc­ture.

An­ti­bod­ies form a Y shape. At the ends of the two arms are loops of pro­tein that latch onto the molec­u­lar tar­get, called an anti­gen. Th­ese loops are called com­ple­men­tar­ity-de­ter­min­ing re­gions, or CDRs. Their struc­ture de­ter­mines which anti­gens it can bind to.

An an­ti­body re­gion called CDR H3 is far longer in cows than in hu­mans, which pro­vides a greater reach to find the right molec­u­lar latch­ing point, such as in a deep in­den­ta­tion that hides a vul­ner­a­ble re­gion.

A broadly neu­tral­is­ing hu­man HIV an­ti­body has an ex­cep­tion­ally long CDR H3 re­gion, but is still much shorter than the one in cows.

In­sights from how cows make th­ese an­ti­bod­ies could help in sev­eral ways.

First, they could give guid­ance in de­vis­ing an ef­fec­tive HIV vac­cine that can quickly rev up the im­mune sys­tem to make th­ese pow­er­ful an­ti­bod­ies, block­ing HIV from get­ting a foot in the door, said Fauci, Bur­ton and Smider.

In ad­di­tion, the broadly neu­tral­is­ing an­ti­bod­ies could be man­u­fac­tured as HIV drugs to pre­vent or treat in­fec­tion, they said.

The an­ti­bod­ies would need to be al­tered to look more hu­man so they don’t pro­voke an im­mune re­ac­tion, but this has been done with other an­ti­body drugs.

Fi­nally, the study could pro­vide a tem­plate for de­vel­op­ing vac­cines and ther­a­pies for other dis­eases, such as in­fluenza.

While HIV and the flu virus are quite dif­fer­ent, the gen­eral con­cept is the same.

The most promi­nent tar­gets on each mu­tate rapidly. Other parts, vi­tal to the virus func­tion, re­main rel­a­tively con­stant but are con­cealed.

The im­mune sys­tem must pro­duce an­ti­bod­ies to the un­chang­ing ar­eas and not be dis­tracted by ar­eas of rapid change.

“A lot of the tools de­vel­oped for HIV are now be­ing ap­plied to flu,” said Fein­berg with the vac­cine ini­tia­tive. A vac­cine for res­pi­ra­tory syn­cy­tial virus, or RSV, may be even closer at hand, he said.

“RSV has been a pathogen which causes se­ri­ous mor­bid­ity and mor­tal­ity in young chil­dren and older peo­ple,” Fein­berg said. “And it’s long been at the top of many lists for vac­cine devel­op­ment, but for a va­ri­ety of rea­sons has been chal­leng­ing.

“I’m hope­ful that th­ese new ap­proaches will ac­tu­ally crack the code on that and en­able the devel­op­ment of an ef­fi­ca­cious RSV vac­cine. So it is a di­rect ex­am­ple where the work in HIV is hav­ing broad ben­e­fits to other ar­eas as well,” he added. – The San Diego Union-Tribune/Tribune News Service

Re­searchers have come up with anti-HIV an­ti­bod­ies from the most un­likely of sources – cows.

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