Below are three articles printed in newservies and the Wall Street Journal describing the Merck vaccine which has recently started early human trials. The purpose of the potential vaccine therapy will be to control HIV with or without HIV antiretroviral therapy. The vaccine does not prevent HIV infection. But preliminary monkey studies showed the vaccine was able to limit HIV to such an extent that it's possible that humans may be able to interrupt HAART after this vaccine therapy. However, research is in the very early stages has not yet tested how much this vaccine can control HIV in humans with HIV. Such tests are planned but it will take at least one year before we have some idea of the potential of this vaccine in humans with HIV. Remember the testing and success so far for this vaccine has been in monkeys so its premature to say it will work in humans.
Experimental AIDS Vaccine
By Will Dunham WASHINGTON (Reuters) April 2, 2001
An experimental AIDS vaccine forged from the virus that causes the common cold blocked the disease from developing into its full-blown stage in laboratory monkeys, although it did not prevent the actual infection, a top scientist at Merck & Co. Inc. said on Monday. The findings point to the potential of a future human AIDS vaccine able to curb the progression of the disease in those infected by HIV, the virus that causes AIDS, said John Shiver, director of vaccine research at Merck Research Laboratories. "Given how dangerous an epidemic this is and the threat it poses to people in general, if our only vaccine is one that controls the infection but does not prevent it, then certainly that's a worthy goal until something comes along that's better," Shiver said in an interview. He also said he could not rule out the possibility that a vaccine following the model used in the study could even protect against initial infection. Shiver said the monkeys were given massive doses of an extremely virulent strain of the virus that causes AIDS, dwarfing the viral exposure experienced by any person who becomes infected.
In a note of caution, he said that any human AIDS vaccine was still years away from being ready. In a study carried out by Merck researchers, rhesus monkeys were infected with a cross between HIV and simian immunodeficiency virus (SIV), the version of the AIDS virus that can infect monkeys and apes. Three monkeys were given the vaccine that used a form of the cold-causing adenovirus that was crippled genetically so it would not reproduce and was made to carry a gene from the AIDS virus.
Vaccinated Monkey "Perfectly
Those three did not develop the damaging aspects of the disease in eight months of observation, suppressing the virus to the point that it no longer was discernible in the bloodstream, Shiver said. "They seem to be perfectly normal -- which does make sense, considering how low the amount of virus is in these animals now," he said. "People with those very low levels typically would not progress to AIDS if they maintained those levels." Six other monkeys were given no vaccine, with five getting the disease and four of those being euthanized, he said. Full-blown AIDS is the last stage of HIV infection. The virus damages cells in the immune system that normally fight off infections and diseases. Typically, HIV lives in an infected person's body for months or years before the appearance of any signs of illness. The Merck team designed the vaccine to elicit so-called cell-mediated immunity -- one of two types of protective responses that can be mounted by the immune system. The body generates cells, called T-lymphocytes, that carry out search and destroy missions for cells already infected by a virus. The researchers said the objective was to stimulate a strong and very specific anti-HIV cellular immune response, as opposed to an antibody response to intercept viruses before they succeed in invading a host cell. The Merck researchers tested five vaccines, with the one involving adenovirus producing the most promising results -- not in preventing infection, but in impeding the progression of the disease. "It certainly is very hopeful. A couple of years ago, there was nowhere near as much reason to feel this kind of hope," Shiver said. "You always have to temper that hope with the realization that it's difficult to translate animal-based studies into humans." The research was discussed at a meeting of AIDS researchers in Colorado (Keystone Conference). It followed recent successes in a similar vein by scientists at Emory University and Harvard Medical School.
Why Merck's Experimental
Vaccine Has Scientific Community So Excited
By MICHAEL WALDHOLZ Staff Reporter of THE WALL STREET JOURNAL
In 1997, Merck & Co. named Emilio Emini to head its struggling effort to find an AIDS vaccine. Dr. Emini had just completed a triumphant assignment: running the research group that discovered and developed the company's protease inhibitor drug that became the critical missing ingredient in the AIDS "cocktail" therapy.
Today, some four years later, Dr. Emini will show how well he's doing. At a science meeting tucked away in a ski resort in the Colorado Rockies, the 47-year-old, Brooklyn native will describe the experiments that led Merck to begin human testing in February of a prototype AIDS vaccine and created a rush of excitement in the global community of AIDS doctors and scientists. The data he will present confirm unofficial information that healthy lab monkeys given the Merck vaccine stayed healthy after a subsequent injection of an AIDS-like virus. These results, first discussed at a closed-door research meeting in January and later reported by The Wall Street Journal, suggest that Merck is furthest along among several relatively new test vaccines intended to protect people against the lethal disease. "The results are very positive," says Norman Letvin, an AIDS vaccine researcher at Boston's Beth Israel Deaconess Medical Center, who was present at the January meeting. "We now need to see if the vaccine can generate a similar immune reaction in humans." The Merck vaccine, made from bits of the AIDS virus stitched into a deactivated common-cold virus, and several others like it face significant hurdles. None seem likely to provide full protection against a viral attack. Instead, if the vaccines work in people as they do in monkeys, they will trigger an immune-system reaction that may simply keep the virus that has invaded the body under control, unable to cause illness or death. Such a partially protective vaccine, while likely to keep an infected person alive for many years without the need for drug therapy, will still pose all sorts of potential concerns that may limit its widespread usefulness or acceptance.
Merck's vaccine also faces at least three years of safety trials before it can be put into a large-scale test of its effectiveness. An efficacy study might take another three to five years to complete. "We are definitely hopeful," Dr. Emini says. But, he pointedly adds, "there's a great deal of difference between testing in primates and testing in people. We're going to do the experiments and wait and see."
The advance by Merck exploits a relatively new understanding of the interaction between the virus and the human immune system that has emerged from numerous labs in the past few years. Based on these findings, researchers are convinced that a vaccine protective against HIV, the AIDS virus, must stimulate the release into the bloodstream of a very specific kind of white blood cell. These so-called CD8 or killer T-cells can seek out cells infected by HIV and destroy them, thereby squelching the virus's ability to replicate and spread. The excitement about the Merck vaccine, and several of the others like it, is that in test tube and animal experiments they all trigger in varying degrees a muscular assault by killer T-cells.
When Dr. Emini joined Merck's vaccine hunt, company researchers and others elsewhere were just beginning to realize that the killer-cell response could be stimulated by exposing human blood to certain of the genes that reside inside the virus. "Emilio got us to focus on developing tests and methods to determine which of these genes generated the best [killer-cell response]," says John Shiver, who already had been working on the vaccine project for three years.
About two years ago, the Merck team decided that proteins produced by three of HIV's internal genes triggered the killer T-cell reaction, and that one of the genes, called "gag," was the most effective. At first, Merck hoped that simply using the genes alone, a technique called naked DNA, would spur the killer-cell response. But in animal tests, the researchers "soon realized that injecting the genes by themselves wasn't getting the strong response we wanted," says Dr. Shiver, 43, who made a separate presentation at the ski-resort meeting this past weekend in Keystone, Colo.
So last year, the Merck researchers decided to take a bold step, one that makes their vaccine different from others in the works. They stitched the internal genes into an adenovirus, a microbe that can cause a nasty bout of the common cold. For its vaccine, Merck has rendered the adenovirus defective, making it incapable of causing either colds or AIDS.
Like other viruses, the adenovirus works by naturally infecting cells; literally transporting its own genes into the inner workings of a target cell. By harnessing this natural viral action, Merck scientists believed they could create an especially effective way to expose the genes to certain immune-system cells that, in turn, signal the release of the killer cells.
In experiments to be presented Monday, Dr. Emini will show that adenovirus-gene combination vaccine provoked a killer-cell response so strong in the monkeys exposed to the AIDS-like virus that they remain healthy even though they still harbor small amounts of the virus.
Merck generated its best results by first "priming" the animals' immune system with the naked DNA containing the gag gene, and following that with a booster shot of adenovirus-containing gene. Merck's human trials, being conducted in several U.S. medical centers, are designed to see if the double inoculation is safe and has the ability to set off a similar killer-cell reaction. If all goes well, Merck will conduct similar safety tests of vaccines containing the other two genes, too. Eventually, it plans to build a vaccine with all three genes.
But because the Merck vaccine and others like it are likely to allow HIV, even in very low levels, to remain inside an exposed person's body, vaccine researchers say more work needs to be done. John Moore, a vaccine researcher at New York's Weill Medical College-Cornell University, says the eventual goal is to create a vaccine that blocks HIV from ever taking hold. Such a vaccine would also have to stimulate what are called neutralizing antibodies that, combined with the killer cells, could be fully protective. But, he says, "we haven't figured out how to produce that kind of antibody reaction yet." Dr. Emini, however, is hopeful the killer-cell response alone may do the trick in people.
Merck & Co. Presents Preclinical Data on HIV Vaccine Program Utilizing CytRx's TranzFect
ATLANTA, April 2 /PRNewswire/
CytRx Corporation today announced that scientists from Merck & Co., Inc. presented data from extensive preclinical studies in their efforts to develop an HIV-1 vaccine, at the Keystone Symposium in Keystone, Colorado. In November 2000, Merck licensed from CytRx the right to use CytRx's TranzFect technology in DNA-based vaccines targeted to four infectious diseases, one of which is HIV.
Dr. John Shiver presented data Saturday evening, March 31, from studies of SHIV89.6P challenge in rhesus monkeys, three months following various vaccination regimens. These studies have shown it possible with different vaccine regimens to markedly reduce the severity of SHIV infection, and progression to AIDS and death, using a highly virulent form of the SHIV virus. (SHIV is a hybrid HIV and simian immunodeficiency virus that infects non-human primates, and is therefore useful for research). These vaccines induced a strong and specific cellular immune response, which appears to have controlled the degree of SHIV infection. It is important to understand that the vaccines did not prevent infection with SHIV. One of the vaccine regimens tested by Merck incorporated CytRx's CRL-1005 compound (TranzFect) as an adjuvant, and was among the most effective regimens, in terms of reducing plasma levels of viral RNA and of preserving levels of rhesus monkey helper T-cells (CD4+ cells) after SHIV infection.
Merck is conducting early (Phase I) clinical trials using novel vaccine technology which hopefully will lead to the development of a vaccine that can effectively prevent (or attenuate) the development of AIDS from HIV infection, as well as treat HIV infection in infected patients taking anti-retroviral therapy. These studies involve the use of vaccine vectors containing the HIV- 1 gag gene that express HIV-1 protein fragments. The intent is to stimulate a strong and specific anti-HIV-1 cellular immune response. The objectives of the studies are to evaluate the vaccine candidates' safety, tolerability and immunogenicity, which is the ability to stimulate an effective cellular immune response.
R. Martin Emanuele, Ph.D., CytRx's Vice President of Research and Business Development, commented, "We are pleased to see that the Merck studies support our belief that TranzFect enhances a critical component of the immune response (cellular immunity) in DNA-based vaccines. We believe these results demonstrate the potential utility of TranzFect in vaccines (such as for cancer and vaccines to control viral diseases) where the enhancement of cellular immunity is critically important."
About CytRx Corporation
CytRx Corporation is a biopharmaceutical company focused on the development and commercialization of high-value human therapeutics. The Company's current research and development activities include CRL-5861, an intravenous agent for treatment of sickle cell disease and other acute vaso- occlusive disorders, and TranzFect, a delivery technology for DNA-based vaccines. CytRx has a research pipeline with opportunities in the areas of muscular dystrophy, cancer, spinal cord injury, vaccine delivery and gene therapy.
This news release may contain forward-looking statements that involve risks and uncertainties. Actual results may differ materially from those discussed in this release due to, among other things, the research, development, and market risks which could adversely affect the Company's timeline for clinical trials, regulatory approval, and, if such approval is received, time to market thereafter. Additional uncertainties and risks are described in the Company's most recently filed SEC documents, such as its Form 10-K and its most recent 10-Q.