No bull

Cat­tle are un­ex­pect­edly good at pro­duc­ing an­ti­bod­ies against HIV and could give in­sight into de­vel­op­ing a vac­cine for hu­mans. Bradley Fikes re­ports.

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How cat­tle help HIV re­search

The prospects for de­feat­ing HIV, once con­sid­ered an in­vin­ci­ble killer, look brighter with ma­jor ad­vances against the Aids-caus­ing virus dis­cussed at an in­ter­na­tional con­fer­ence re­cently.

One of those pieces of good news comes from the Scripps Re­search In­sti­tute in La Jolla, Cal­i­for­nia. In col­lab­o­ra­tion with the In­ter­na­tional Aids Vac­cine Ini­tia­tive, its re­searchers have gen­er­ated ‘‘broadly neu­tral­is­ing an­ti­bod­ies’’ that kill HIV us­ing an un­ex­pected source – cat­tle.

The star­tling feat was an­nounced in a study pub­lished in the jour­nal Na­ture. It marks an­other mile­stone step to­wards the long-elu­sive aim of cre­at­ing a vac­cine against the virus, with the an­ti­bod­ies per­haps also lead­ing to the 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, coau­thor of the new re­port and a long­time re­searcher of such an­ti­bod­ies at the Scripps Re­search.

In other news at the nineth 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.

‘‘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.’’

Across the globe, 37 mil­lion peo­ple are liv­ing with HIV, with many 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 2.1m new in­fec­tions oc­curred world­wide in 2015, ac­cord­ing to the Na­tional In­sti­tute for Al­lergy and In­fec­tious Dis­eases.

In New Zea­land, in­fec­tion rates are climb­ing. In 2016, 244 peo­ple were di­ag­nosed with HIV com­pared with 224 in 2015, ac­cord­ing to fig­ures from Otago Univer­sity’s Aids Epi­demi­ol­ogy Group. About 3500 peo­ple are es­ti­mated to be liv­ing with HIV here. Glob­ally, more than 70m peo­ple have been in­fected with HIV, ac­cord­ing to the World Health Or­gan­i­sa­tion. About 35m 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 have 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 wellestab­lished to erad­i­cate from the pa­tient’s body, said Dr An­thony Fauci, di­rec­tor of the Na­tional In­sti­tute of Al­lergy and In­fec­tious Dis­eases in the US. 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. 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.

In­sights from how cat­tle 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.

At Scripps Re­search, Bur­ton and col­leagues have been ex­am­in­ing broadly neu­tral­is­ing an­ti­bod­ies for decades, seek­ing ev­i­dence of a po­ten­tial vac­cine in­gre­di­ent. The goal is to com­press the years of ‘‘ed­u­cat­ing’’ the hu­man im­mune sys­tem into months, through a se­ries of vac­ci­na­tions us­ing frag­ments of HIV along with other sub­stances to stim­u­late an im­mune re­sponse.

An­other part of this re­search is fig­ur­ing out why the hu­man im­mune sys­tem is so bad at fight­ing HIV, com­pared to other viruses, Fauci said. The cat­tle an­ti­body re­search is use­ful as a con­cep­tual tool.

‘‘If we can fig­ure out the way that (HIV) pro­tein in­ter­acts with the cow’s im­mune sys­tem that al­lows the cow to make such great an­ti­bod­ies against HIV, and to do it so read­ily and quickly and in abun­dance, it may give us some in­sight into how we can de­velop an HIV vac­cine in a hu­man,’’ Fauci said. – MCT

"To me, the most sig­nif­i­cant thing is how the epi­demic con­tin­ues to rav­age many coun­tries and com­mu­ni­ties." Mark Fein­berg

Calves were in­jected with HIV frag­ments se­lected to pro­voke pro­duc­tion of ‘‘broadly neu­tral­is­ing an­ti­bod­ies’’. Their quick re­sponse was re­mark­able, es­pe­cially com­pared with the slow hu­man re­sponse.

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