The most recent statistics, more than a year out of date, show that there were over 40 million people worldwide living with Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS). Today that number may be between 60 and 80 million.
In the not-so-distant future, however, this global epidemic may be a thing of the past. A team of researchers led by scientists at the Institute of Human Virology (IHV) based at the University of Maryland at Baltimore have taken the monumental first step in creating an animal vaccine which has neutralizing effects on HIV.
According to Dr. Robert Gallo, codiscoverer of the HIV virus and director of the Institute of Human Virology, "This is one of the more exciting findings that I have witnessed in HIV/AIDS research since the early days when it seemed scientific advances were announced regularly."
The paper published in U.S. Proceedings in the National Academy of Sciences (PNAS) on Sept. 3, 2002, was authored by Drs. Timothy Fouts and Anthony Devico at the IHV, as well as Dr. Ranajit Pal at Advanced BioScience Laboratories, Inc., and their colleagues.
HIV, which is transmitted primarily through sexual contact and sharing needles, is a retrovirus. This means that HIV's genome is contained in single-stranded RNA. The HIV genome is located in an envelope, containing a surface protein called gp120. Gp120 molecules bind to CD4 molecules on the surface of helper T-cells. The gp120 molecules then bind to a second co-receptor, before the HIV genetic materiel is injected into the cell. Inside the cell, the RNA is retro-transcribed, turning it into DNA, and then inserted into the host's cell DNA. The virus is then replicated and repackaged to continue infection.
As the HIV infection progresses, the number of cells containing CD4 drops, because the virus is destroying the immune system. A non-infected individual would have between 500 and 1500 of these cells in a milliliter of blood. The HIV virus has lead to AIDS when the infected individual has a CD4 count below 200.
These scientists took a novel approach for this vaccine. Instead of using gp120 alone in a vaccine, the group used a form of gp120 covalently linked to CD4 to increase CD4's affinity for the envelope glycoprotein. The binding between gp120 and CD4 leads to conformational changes in the protein complex. This means that the antibodies raised will recognize gp120 when it is bound to CD4. The aim is to allow the body to intercept the virus after it first binds to CD4, but before it infects the cell.
The study examined whether or not this vaccine approach lead to the neutralization of primary HIV isolates: strains of the virus derived from infected individuals. No vaccine trial thus far has been able to completely obliterate the infecting virus; all efforts simply helped to boost the immune response. However, in the rhesus macaques animal model that was used, the vaccine in question was able to illicit a neutralizing response against a broad spectrum of primary strains.
According to Dr. Devico, "The gp120-CD4 complex has shown a consistent ability to generate antibodies that neutralize a wide range of HIV-1 isolates ? The preliminary findings indicate the gp120-CD4 complex might serve as a useful model for HIV vaccine development."
While traditionally the focus for stopping the AIDS epidemic has been on therapy, it seems as if a preventative vaccine might be a better direction to go in.
Dr. George Lewis, Director of the IHV's Division of Vaccine Development explains that "While advances in therapeutics are helping many with the disease live longer and healthier lives ? most of the world lacks these resources and our best bet to stop the AIDS epidemic is a vaccine. We hope this will become an effective tool toward that global goal."
As the epidemic progresses to uncharted territory, there may in fact be a need for a vaccine designed as a preventative measure to take on therapeutic roles, as well.
Dr. Lewis describes the current status of HIV-infection worldwide, saying "HIV/AIDS has overcome the 1918 influenza pandemic and bubonic plague of the 14th century to become the worst epidemic and deadliest disease in medical history. Twenty-five million persons have died worldwide, another 40 million are infected and the numbers are rapidly escalating second to second."
"The difficulties [in developing a preventative vaccine] have been many, spanning close to two decades. But this has the potential to bring us a major step forward in that ultimate quest," according to Dr. Gallo.
The IHV is involved in some truly cutting-edge research; despite its affiliation with the University of Maryland, Johns Hopkins students, including undergraduates, are still able to conduct research at the institute.
Although the vaccine has only been tested in animals, the researchers are aiming at beginning Phase I clinical trials in humans within the next two years.
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