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Un vaccin universel contre le VIH (sida) aurait été mis au point

samedi 28 février 2015, par anonyme (Date de rédaction antérieure : 28 février 2015).

http://www.science-et-vie.com/2015/…

Publié le 21/02/2015

Román Ikonicoff

Des virus HIV (en jaune) en train d’infecter une cellule T humaine (Ph. NIH)

Un article paru dans la revue Nature annonce la mise au point d’un vaccin contre le VIH, le rétrovirus du sida, sous toutes ses variantes transmissibles à l’homme et dont la durée d’action dépasserait 8 mois. Un travail qui devrait être largement commenté lors de la Conférence sur les rétrovirus et les infections opportunistes (CROI), qui se tiendra à Seattle (Washington) entre le 23 et le 26 février.

L’article, signé par des chercheurs d’une douzaine de centres de recherche, décrit comment leur nouvelle substance, une protéine, est capable de bloquer simultanément deux sites actifs de la surface des virus de souche VIH-1, VIH-2 et VIS (virus du sida des singes) rendant impossible leur pénétration dans les lymphocytes CD4 du système immunitaire humain, les premières cellules à être infectées par le virus.

Vaincre le sida avec ses propres armes

En effet, les virus du sida fusionnent avec la membrane des CD4 et injectent dans ces cellules leur matériel génétique transformant leur hôte en une usine à VIH, lesquels donc finissent par infecter tous les autres cellules du système immunitaire : celui-ci est alors détruit. Des lors, des infections opportunistes, habituellement inoffensives pour un organisme en bon état, deviennent mortelles.

Selon les chercheurs, le vaccin serait actif durant au moins 8 mois – et peut-être plusieurs années – via un mécanisme de réplication de la protéine bloquante inspiré par le mode de reproduction du VIH lui-même. De fait, par manipulation génétique, les chercheurs ont transformé un adénovirus relativement inoffensif en usine à protéines bloquantes : une fois injectés dans un muscle humain, ces adénovirus sont capables de produire en continu ces protéines, qui vont donc systématiquement fusionner avec la membrane des VIH et bloquer leur action. Les VIH qui ont pénétré dans le corps ne peuvent se reproduire : ils meurent et l’infection disparaît.

Des avancées fulgurantes ces dernières années

Cela fait quelques années que le monde de la recherche médicale annonce des avancées fulgurantes dans le traitement de l’infection par VIH, en particulier la mise au point de vaccins. Par exemple, en janvier dernier Science & Vie avait informé de la mise au point par des chercheurs du laboratoire GSK d’un vaccin pouvant bloquer l’infection pendant trois mois grâce à l’utilisation d’une substance chimique, un antirétroviral, associé à une nanoparticule à diffusion lente.

Mais le nouveau traitement présenté dans Nature, encore en phase d’expérimentation chez le singe, s’attaque au VIH avec des armes semblables : l’utilisation d’une cellule (ici, un adénovirus) comme système de réplication. Un bel espoir de vaincre le sida sur son propre terrain.


Scientists announce anti-HIV agent so powerful it can work in a vaccine

http://www.sciencedaily.com/releases/2015/02/150218073059.htm

Date : February 18, 2015
Source : The Scripps Research Institute
Summary : In a remarkable new advance against the virus that causes AIDS, scientists have announced the creation of a novel drug candidate that is so potent and universally effective, it might work as part of an unconventional vaccine.

Scanning electron micrograph of HIV particles infecting a human T cell.

Credit : NIH

In a remarkable new advance against the virus that causes AIDS, scientists from the Jupiter, Florida campus of The Scripps Research Institute (TSRI) have announced the creation of a novel drug candidate that is so potent and universally effective, it might work as part of an unconventional vaccine.

The research, which involved scientists from more than a dozen research institutions, was published February 18 online ahead of print by the journal Nature.

The study shows that the new drug candidate blocks every strain of HIV-1, HIV-2 and SIV (simian immunodeficiency virus) that has been isolated from humans or rhesus macaques, including the hardest-to-stop variants. It also protects against much-higher doses of virus than occur in most human transmission and does so for at least eight months after injection.

"Our compound is the broadest and most potent entry inhibitor described so far," said Michael Farzan, a TSRI professor who led the effort. "Unlike antibodies, which fail to neutralize a large fraction of HIV-1 strains, our protein has been effective against all strains tested, raising the possibility it could offer an effective HIV vaccine alternative."

Blocking a Second Site

When HIV infects a cell, it targets the CD4 lymphocyte, an integral part of the body’s immune system. HIV fuses with the cell and inserts its own genetic material — in this case, single-stranded RNA — and transforms the host cell into a HIV manufacturing site.

The new study builds on previous discoveries by the Farzan laboratory, which show that a co-receptor called CCR5 contains unusual modifications in its critical HIV-binding region, and that proteins based on this region can be used to prevent infection.

With this knowledge, Farzan and his team developed the new drug candidate so that it binds to two sites on the surface of the virus simultaneously, preventing entry of HIV into the host cell.

"When antibodies try to mimic the receptor, they touch a lot of other parts of the viral envelope that HIV can change with ease," said TSRI Research Associate Matthew Gardner, the first author of the study with Lisa M. Kattenhorn of Harvard Medical School. "We’ve developed a direct mimic of the receptors without providing many avenues that the virus can use to escape, so we catch every virus thus far."

The team also leveraged preexisting technology in designing a delivery vehicle — an engineered adeno-associated virus, a small, relatively innocuous virus that causes no disease. Once injected into muscle tissue, like HIV itself, the vehicle turns those cells into "factories" that could produce enough of the new protective protein to last for years, perhaps decades, Farzan said.

Data from the new study showed the drug candidate binds to the envelope of HIV-1 more potently than the best broadly neutralizing antibodies against the virus. Also, when macaque models were inoculated with the drug candidate, they were protected from multiple challenges by SIV.

"This is the culmination of more than a decade’s worth of work on the biochemistry of how HIV enters cells," Farzan said. "When we did our original work on CCR5, people thought it was interesting, but no one saw the therapeutic potential. That potential is starting to be realized."

In addition to Farzan, Gardner and Kattenhorn, authors of the study, "AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges," include Hema R. Kondur, Tatyana Dorfman, Charles C. Bailey, Christoph H. Fellinger, Vinita R. Josh, Brian D. Quinlan, Pascal Poignard and Dennis R. Burton of TSRI ; Jessica J. Chiang, Michael D. Alpert, Annie Y. Yao and Ronald C. Desrosiers of Harvard Medical School ; Kevin G. Haworth and Paula M. Cannon of the University of Southern California ; Julie M. Decker and Beatrice H. Hahn of the University of Pennsylvania ; Sebastian P. Fuchs and Jose M. Martinez-Navio of the University of Miami Miller School of Medicine ; Hugo Mouquet and Michel C. Nussenzweig of The Rockefeller University ; Jason Gorman, Baoshan Zhang and Peter D. Kwong of the National Institutes of Health ; Michael Piatak Jr. and Jeffrey D. Lifson of the Frederick National Laboratory for Cancer Research ; Guangping Gao of the University of Massachusetts Medical School ; David T. Evans of the University of Wisconsin ; and Michael S. Seaman of Beth Israel Deaconess Medical Center.

The work was supported by the National Institutes of Health (grants R01 AI091476, R01 AI080324, P01 AI100263, RR000168 and R01AI058715).

Story Source : The above story is based on materials provided by The Scripps Research Institute. Note : Materials may be edited for content and length.

Journal Reference :

  • 1 Matthew R. Gardner, Lisa M. Kattenhorn, Hema R. Kondur, Markus von Schaewen, Tatyana Dorfman, Jessica J. Chiang, Kevin G. Haworth, Julie M. Decker, Michael D. Alpert, Charles C. Bailey, Ernest S. Neale, Christoph H. Fellinger, Vinita R. Joshi, Sebastian P. Fuchs, Jose M. Martinez-Navio, Brian D. Quinlan, Annie Y. Yao, Hugo Mouquet, Jason Gorman, Baoshan Zhang, Pascal Poignard, Michel C. Nussenzweig, Dennis R. Burton, Peter D. Kwong, Michael Piatak, Jeffrey D. Lifson, Guangping Gao, Ronald C. Desrosiers, David T. Evans, Beatrice H. Hahn, Alexander Ploss, Paula M. Cannon, Michael S. Seaman, Michael Farzan. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature, 2015 ; DOI : 10.1038/nature14264

Michael Farzan is a professor at the Florida campus of The Scripps Research Institute.


The image shows the part of HIV – shown in beige – that attaches to two receptors, CD4 and CCR5. Scripps Research Institute scientists and colleagues developed a drug candidate that binds both sites simultaneously. The drug includes part of CD4 (red), connected to a mimic of CCR5 (green). These parts are connected by a conserved piece of an antibody (gray). Because the inhibitor binds both sites simultaneously, it binds tightly and triggers the virus to change its shape, blocking HIV-1 more effectively than any currently available antibody therapy.


About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

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