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New approach to blocking HIV raises hopes for AIDS vaccine

By Emeka Anuforo (Abuja) with New York Times report
19 February 2015   |   9:34 pm
• Veterinarians alert as bird flu hits 17 states • Want animal disease control law reviewed • Canvass compensation for affected farmers • No report of ailment in humans yet  A NEW compound has blocked Human Immuno-deficiency Virus (HIV) infection so well in monkeys that it may be able to function as a vaccine against Acquired Immune Deficiency…

HIV

• Veterinarians alert as bird flu hits 17 states • Want animal disease control law reviewed • Canvass compensation for affected farmers • No report of ailment in humans yet 

A NEW compound has blocked Human Immuno-deficiency Virus (HIV) infection so well in monkeys that it may be able to function as a vaccine against Acquired Immune Deficiency Syndrome (AIDS), the scientists who designed it reported midweek. The study was published online by the journal Nature. 

  Meanwhile, the Nigerian Veterinary Medical Association (NVMA) yesterday issued concerns over the Highly Pathogenic Avian Influenza (HPAI) resurgence in the country.

    While the association is optimistic that if Nigeria works together as a nation, it could conquer the disease like the Ebola Virus Disease; it also called on all veterinary doctors to consider the resurgence of the disease, also known as Bird Flu, as a professional challenge and should quickly rise to the occasion.

  HIV has defied more than 30 years of conventional efforts to fashion a vaccine. The new method stimulates muscle cells to produce proteins that somewhat resemble normal antibodies, which have Y-shaped heads. These proteins have both a head and a tail, and they use them to simultaneously block two sites on each “spike” that the virus uses to attach itself to a cell.

  If both sites can be blocked on every spike, the virus becomes helpless and drifts off unattached into eventual oblivion by the immune system.

  Director of the National Institute of Allergy and Infectious Diseases (NIAID) United States, which supported the work, Dr. Anthony S. Fauci, said: “It’s a twofer. It’s very impressive, and the method is quite promising. But it’s still just in an animal model, so we’ll need to see evidence of whether it works in humans.”

  The technique, the paper’s lead author said, had completely protected four monkeys for nearly a year against repeated attempts to infect them with large doses of several strains of SHIV, a version of HIV adapted for use in lab monkeys.

  The author, Michael Farzan, an infectious disease specialist at the Scripps Research Institute in Florida, described the new compound as “the broadest and most potent entry inhibitor described so far.”

  It is simpler and works better, he said, than the current method that scientists are experimenting with: giving monkeys cocktails of several different antibodies that each neutralise only one or two strains of HIV, sometimes imperfectly.

  Describing over the telephone the way his new compound worked, Farzan said that he was bending his hand into a claw, with his thumb representing the end blocking one site and two fingers blocking the other.

  “One of my colleagues told me it’s the grip for a two-seam cut fastball,” he said.

  The work was led by scientists at his institute but involved researchers from Harvard, Princeton, Rockefeller University, the University of Southern California, the Pasteur Institute in France and elsewhere.

  The next step, Farzan said, would be to test the compound in infected monkeys and see if it could stop the virus from replicating further, which is what antiretroviral medicines do. If that proves safe and effective, he said, he hoped to start human trials in three stages.

  In the first, humans would be injected every few weeks with just the antibody-like protein, not with the vector that stimulates muscle cells to produce it. If that were successful, the vector would be injected into humans who already have HIV, but are not taking antiretroviral pills because they refuse, forget or experience bad side effects.

  Finally, the compound would be given to healthy people at high risk – such as gay men who have frequent unprotected sex with strangers – to see if it protects them.

  The new approach uses cutting-edge techniques that are not widely known, or even entirely understood, by the scientists experimenting with them.

  Historically, vaccines have been made by killing or weakening whole viruses and injecting them; that stimulates the immune system to produce antibodies that recognise and attack the real virus when it arrives.

  Newer vaccines splice genes for particular antibodies into other weakened viruses. Generally, the genes are carried into a cell by the virus, incorporated into the cell’s genome, and begin producing the necessary antibodies.

  But this new method splices the desired gene into a stretch of DNA so short that it cannot function like a virus at all and does not deserve to be called one, Farzan said, who referred to it simply as “a gene therapy vector.” It does not integrate itself into the DNA of a cell or replicate itself. 

  Nonetheless, injecting that vector into muscle stimulates cells to produce the antibody-like protein encoded by the gene.

  “Why? We’re not really able to answer that question,” Farzan said. “But it does.”

  HIV normally targets CD4 cells, white blood cells that act as the sentinels of the immune system.

  The virus invades them by attaching its outer spikes – known as envelope proteins – to two different receptors on the outside of the cell. First it attaches to the CD4 receptor; that exposes the CCR5 receptor. Once attached to both, the virus can inject its RNA into the cell and hijack its inner machinery to produce more viruses.

  But the protein produced by Farzan, bent into its claw shape, blocks both the CD4-binding site and the CCR5-binding site. It does so in a very tight “match” difficult for the virus to block by means of “escape mutations” – changes in shape that partly prevent engineered antibodies from attaching.

  “It fools the virus into thinking it’s interacting with a cell,” Farzan said.

  Dr. Philip R. Johnson, director of the Children’s Hospital of Philadelphia Research Institute and the inventor of the vector that Farzan used, called the new approach “good stuff.”

  “It appears to be as good as, if not better than, anything else that’s being tried,” he said.

  Eventually, he said, he would like to see an approach that combined known antibodies and the new protein “so we could target two or three areas on the virus.”

  In a chat with journalists in Abuja, National President of the Association, Dr. Edgar Amos Sunday, also called for the review and streamlining of the Animal Disease (Control) Decree of 1988 to suite contemporary realities.

Measures to check spread

The NVMA further stressed that poultry meat and eggs should be hygienically processed, noted that if well-cooked, is safe for human consumption.

  The body also weighed the scientific and other arguments concerning the use of vaccines for Bird Flu and suggested that government’s current policy against vaccination as a strategy in the control of bird flu should be sustained.

  Sunday urged the public not to panic, but called on poultry farms to ensure strict monitoring and restriction of movement of people and items such as crates, bags and so on, especially between farms. The association also canvassed strict hygiene before and after handling poultry.

  He added: “Cases of ill health in poultry should be reported immediately to the nearest veterinary clinic.

  “The Avian Influenza Control Project structures in various states should be strengthened and equipped to carry out public enlightenment, surveillance, depopulation, disinfection and so on. State governments in particular should invest more in providing and upgrading veterinary infrastructure.  Active surveillance should be carried out immediately throughout the country even in states where the disease has not been reported. This is to facilitate movement ahead of the virus.

  “More veterinary doctors should be employed by government. The situation in some states that have less than 10 veterinary doctors in their service is inimical to both animal and public health. Such states cannot effectively deliver health service and control of diseases like bird flu.”

  He further stressed: “More veterinary hospitals, clinics and laboratories should be constructed while existing ones should be rehabilitated and equipped. Specifically, the National Veterinary Research Institute (NVRI) laboratory in Vom and its branches should be supported to enhance the capacity for quick and accurate diagnosis of bird flu and other diseases. Development partners should lend their support in these regard.

  “Standard operational procedures for poultry business should be re-designed and implemented.”

  He called on government to provide sufficient funds for the payment of compensation to farmers whose poultry had been depopulated.

Current situation 

Sunday disclosed: “The current outbreak was first reported from a commercial farm in Kano on December 24, 2014 and a live bird market at Onipanu in Lagos on January 8, 2015. This was confirmed by the NVRI, Vom. As at February 18, the disease had been confirmed in 17 states nationwide. These are Kano, Lagos, Ogun, Rivers, Delta, Plateau, Edo, Gombe, Imo, Oyo, Jigawa, Kaduna, Bauchi, Zamfara, Katsina, Sokoto and Anambra.

  “The confirmed cases are from 146 poultry farms, 10 live bird markets and 11 zoological gardens spread in 61 local government areas. There has not been any reported case of bird flu so far in humans in the country and all human samples have so far tested negative.”

  He stressed, however, that the prospects for containment were bright despite the implications of bird resurgence in Nigeria

  “The experience, technical manpower, facilities and support used in containing the 2006 outbreak is accessible,” he added.

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