first_imgFor 30 years, researchers have struggled to determine which immune responses best foil HIV, information that has guided the design of AIDS vaccines and other prevention approaches. Now, a research team has shown that a lab-made molecule that mimics an antibody from our immune system may have more protective power than anything the body produces, keeping four monkeys free of HIV infection despite injection of large doses of the virus. Intensive hunts are under way for natural HIV antibodies that can stop—or “neutralize”—the many variants of the constantly mutating AIDS virus. Researchers have recently found several dozen broadly neutralizing antibodies (bNAbs) that are highly potent and work at low doses. But viral immunologist Michael Farzan of the Scripps Research Institute in Jupiter, Florida, and 33 co-workers have recently taken a different strategy, building a novel molecule based on our knowledge of how HIV infects cells. HIV infects white blood cells by sequentially attaching to two receptors on their surfaces. First, HIV’s own surface protein, gp120, docks on the cell’s CD4 receptor. This attachment twists gp120 such that it exposes a region on the virus that can attach to the second cellular receptor, CCR5. The new construct combines a piece of CD4 with a smidgen of CCR5 and attaches both receptors to a piece of an antibody. In essence, the AIDS virus locks onto the construct, dubbed eCD4-Ig, as though it were attaching to a cell and thus is neutralized.In test-tube experiments, eCD4-Ig outperformed all known natural HIV antibodies at stopping the virus from infecting cells, Farzan’s team reports in this week’s issue of Nature. To test how it works in animals, they then put a gene for eCD4-Ig into a harmless virus and infected four monkeys; the virus forces the monkey’s cells to mass produce the construct. When they “challenged” these monkeys and four controls with successively higher doses of an AIDS virus for up to 34 weeks, none of the animals that received eCD4-Ig became infected, whereas all of the untreated ones did.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)The new study ups the ante on a similar gene therapy approach with natural antibodies that 6 years ago showed promise in monkey experiments, says an accompanying Nature editorial by AIDS vaccine researcher Nancy Haigwood of Oregon Health & Science University in Beaverton. “I am a huge fan of this paper,” Haigwood says. “It’s really very creative and a breakthrough as far as I am concerned.” Pediatrician Philip Johnson of the Children’s Hospital of Philadelphia in Pennsylvania, whose lab in 2009 showed success with a gene therapy that delivers an HIV bNAb, adds that eCD4-Ig “is a beautiful thing.”Building on work by Johnson’s group, Farzan’s team stitched the gene for eCD4-Ig into an adeno-associated virus (AAV) that is harmless to humans. Those viruses, injected into monkey muscles, continued to produce eCD4-Ig for the 40 weeks of the experiment. “Everyone expects with AAV that this can go on forever,” Farzan says. The animals had no detectable immune response against the eCD4-Ig, presumably because it is so similar to pieces of their own cells.Not everyone is convinced that eCD4-Ig will ultimately work better than natural HIV antibodies. Virologist David Baltimore, a Nobel laureate based at the California Institute of Technology in Pasadena, is working with a group developing its own AAV gene therapy that delivers an HIV bNAb. He describes the eCD4-Ig chimera and the paper as “impressive” and says he welcomes this new approach. But Baltimore, who like Johnson has already moved into early phase human trials with his gene therapy, notes that the new work offers only test-tube and animal data. “It’s perhaps a better construct than the antibodies we’ve been using, but it’s a matter of how it plays out in human trials,” Baltimore says. “I don’t think it’s easy to tell how that will happen.”Johnson agrees that eCD4-Ig may not work as well as bNAbs in humans, but also says the natural antibodies, even if they have less potency and breadth, may be powerful enough to stop HIV. “How good is good enough?” Johnson asks. “Nobody has a clue about that. The only way you would know really is to do a bake-off in a human trial.”Farzan says in theory at least, it will be harder for the virus to mutate its way around eCD4-Ig than a bNAb, because HIV needs to bind to CD4 and CCR5. Whether any of these gene therapies will prove safe and practical remains to be seen. Farzan, for his part, has more experiments planned before moving into humans. “We need to do a lot more monkey studies to see if there’s anything weird,” he says.last_img read more

first_imgDarjeeling: The Hills were a witness to postering by the Gorkha Janmukti Morcha (Binay Tamang faction) against BJP state president Dilip Ghosh’s alleged anti-Gorkhaland comments.”The BJP always does a U turn on their pre-poll commitments,” alleged Binay Tamang, President, Gorkha Janmukti Morcha (GJM.) “The Gorkhas feel let down. Every time during election the BJP asks for votes in the name of Gorkhaland and after winning they take a U turn. We strongly condemn this,” stated Tamang, talking to media persons in Pintail Village near Siliguri on Wednesday. Also Read – Rs 13,000 crore investment to provide 2 lakh jobs: MamataThe GJM President was referring to BJP West Bengal State President Dilip Ghosh’s statement regarding Gorkhaland. Ghosh talking to media persons in Jalpaiguri on Sunday had clearly stated that his party has made no commitments regarding the creation of Gorkhaland. “We are sympathetic to Gorkhaland demand. We want development of the Gorkhas but we had never promised a separate state,” claimed Ghosh. Tamang said not only the Gorkhaland issue, but the BJP has let down the people of the Hills in other issues too. Also Read – Lightning kills 8, injures 16 in state”Darjeeling MP Raju Bista had questioned the Tribal Minister in Parliament regarding the granting of tribal status to the 11 sub communities of the Gorkhas in question number 2351,” stated Tamang. Answering this question, Renuka Singh Saruta Minister of State for Tribal Affairs said there are certain modalities for deciding the claims for inclusion or exclusion or changes in the Schedule Caste, Schedule Tribe lists. “As per the modalities only those proposals which have been recommended and justified by the concerned State Government/ UT Administration and concurred with by the Registrar General of India (RGI) and National Commission for Scheduled Tribes (NCST) are to be considered and legislation amended. The committee submitted its report which was referred to the ORGI for comments. ORGI have commented that the report of the said Committee is beyond the scope of the Modalities approved by the Government of India with regard to inclusion of any community in the ST list of a state,” stated the minister. Regarding the Central University question (question 3432) raised by Raju Bista in Parliament, Ramesh Pokhriyal “Nishank,” Minister of Human Resource Development stated: “There is no proposal to set up a new Central University in Darjeeling.”Education is a concurrent subject. State Government also take initiatives to enhance the access to higher education in their respective states along with other private universities/ Institutions,” stated the HRD Minister. “We have been let down by the BJP in all three issues namely Gorkhaland, inclusion of Gorkha sub communities in the ST list and Central University in Darjeeling,” stated Tamang.last_img read more