When people began to develop acute immune deficiency syndrome and die, horror was the feeling of humans allover the world. Nobody had yet known the cause of the catastrophe and no science could deliver any explanation. When the explanation emerged, the horror became a double horror for those who found out that the culprit is a new virus that has the ability to destroy the immune system and its presence is a death sentence. For a few years, patients died by the thousands without any hope without treatments and with the first generation treatments. The side effects of the combination drugs given at the time were bitter honey that offered sweet unreliable hope and bitter devastation and despair.
It was real horror for the patients, their relatives and friends until the advancement in molecular biology and biotechnology began to yield drugs that turned the desperation into real hope. The improvement on these products by companies like Gilead (GILD) contributed to patients’ well being and to a better prognosis for the devastating disease. HIV patients are now living almost a normal life, but unfortunately, no protective vaccines and no cures have succeeded in reaching the market. All attempts to developing vaccines have failed and all promises of cures have died in experimentation. The mini HIV creature has been capable of evading all scientists’ creative means to prevent it from destroying human immune system cells.
Suddenly, and unexpectedly, last Thursday morning, we opened our eyes on breathtaking news from the National Institute of Health (NIH). The NIH announced the discovery of two natural antibodies that can prevent 90% of known HIV strains from infecting cells. A study detailing the research was published in the online edition of the journal Science. The unexpected pleasurable news made us feel, for the first time in years, that humans are finally on the most relevant path towards beating HIV at its own game. We felt that we are on the brink of winning the quarter of a century war between the human mind and the invisible mindless HIV creature, which used its built in instinctive savoir-faire in dismantling millions of human immune systems while protecting itself against all kinds of attempts to assassinate it, or prevent it from causing what medical literature call acquired immune deficiency syndrome (AIDS), killing millions of victims. The NIH news hinted that the research would probably lead to the development of far-reaching HIV preventive vaccines and treatments.
Like all stories of breakthrough achievements, the hero behind this story is the privilege restricted to humans known as curiosity. NIH’s scientists’ curiosity has led them to observe that a few HIV-infected patients have not developed AIDS. They called those patients, non-progressors. It was obvious that the lucky few must have something unique in their immune system that would prevent the virus from invading their immune system cells. Motivated still by academic curiosity, the scientists were determined to unearth the reasons behind the strange phenomenon.
Together with other scientists from various medical and research institutions, the NIH team used a novel molecular device that consists of an HIV protein they modified so it would react only with antibodies specific to the CD4 binding site of HIV. The trick worked. Two antibodies, VRC01 and VRC02 did attach to the protein. The scientists then determined the atomic-level molecular structure of VRC01 when attached to the CD4 binding site. The findings enabled them to learn the structure of the discovered natural antibodies. It is important to know that the CD4 binding site of the virus does not mutate, which explains the reason that the discovered natural antibodies are capable on neutralizing the effects of a vast majority of HIV strains.
The information was sufficient for the scientists to begin designing components of a candidate vaccine that could stimulate the human immune system to make the natural antibodies, which would prevent infection by many HIV strains worldwide. Developing vaccines to produce the natural antibodies face some technological challenges. The leader of the research, Dr. Kwong, and his colleagues explored how this challenges might be addressed by designing vaccine components that could guide the immune system through the stepwise antibody maturation process, hence, facilitating the generation of a VRC01 antibody from its precursors. Another suggested possibility is designing gene therapy where a gene can express one of the antibodies, probably, VRC01.
The reason for the failure of the naturally occurring antibodies in protecting the majority of patients is that the immune system usually produces them after the patients are infected. In HIV, the virus has the advantage of debilitating the immune system before the protective antibodies go into action.
Dr. Gary Nabel, the National Institute of Allergy and Infectious Diseases said:
"I am more optimistic about an AIDS vaccine at this point in time than I have been probably in the last 10 years. Two natural antibodies can attach to and neutralize 90 percent of the various mutations of the human immunodeficiency virus that causes AIDS.
“We have used our knowledge of the structure of a virus—in this case, the outer surface of HIV—to refine molecular tools that pinpoint the vulnerable spot on the virus and guide us to antibodies that attach to this spot, blocking the virus from infecting cells.”
"This is an antibody that evolved after the fact. That is part of the problem we have in dealing with HIV -- once a person becomes infected, the virus always gets ahead of the immune system. What we are trying to do with a vaccine is to get ahead of the virus."
Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, said:
The discovery of these exceptionally broadly neutralizing antibodies to HIV and the structural analysis that explains how they work are exciting advances that will accelerate our efforts to find a preventive HIV vaccine for global use.” In addition, the technique the teams used to find the new antibodies represents a novel strategy that could be applied to vaccine design for many other infectious diseases.”
Dr. Mascola, the deputy director of the VRC, said:
“The antibodies attach to a virtually unchanging part of the virus, and this explains why they can neutralize such an extraordinary range of HIV strains.”
Dr. Kwong who led the team at the NIH said,
“The discoveries we have made may overcome the limitations that have long stymied antibody-based HIV vaccine design.”
Research teams: The researchers included NIAID scientists from the VRC, the Laboratory of Immunoregulation, and the Division of Clinical Research, all in Bethesda, Md.; researchers from Beth Israel Deaconess Medical Center in Boston; Columbia University in New York; Harvard Medical School and Harvard School of Public Health in Boston; The Rockefeller University in New York City; and University of Washington in Seattle.
Wu X et al. Rational design of envelope surface identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. DOI: 10.1126/science.1187659 (2010).
Zhou T et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. DOI: 10.1126/science.1192819 (2010).
This is good news. It offered insightful research, very promising results and suggestions for far-reaching treatments. We do not know which one of the drug designers and developers has helped design and develop the molecules used in the NIH experimentation and we do not know who will develop the therapeutic molecules or the vaccine. But we certainly know that these tasks are none of academia or government businesses. They are the specialty of drug developers that have state-of-the-art drug design and monoclonal antibody technology. There is no doubt that the NIH information has brought new possibilities for the drug developers that are interested in conquering HIV.
We take advantage to recognize the fact that the successful NIH research would not have been possible if not for the accumulated data from the previously failed attempts to develop HIV preventive and therapeutic vaccines. Some of the companies that spent a lot of effort and money on their unsuccessful attempts might have failed to survive, but their efforts have not gone to the drain. For scientists, data from failed experiments are cause for improvement. Data about failed trials are teaching treasures. They teach scientists the reasons for previous failures. They alert them against scientific mistakes that could jeopardize their efforts. They open scientists’ minds to scientific and procedural facts that are usually introduced to science after failed trials.
Before we forget, we have to admit that the firms developing the current HIV treatments have rescued millions of patients from agony and death. The world should be grateful to: Gilead (GILD), Vertex (VRTX), Abbott Laboratories (ABT), Bristol-Myers Squibb (BMY) Roche (RHHBY), GlaxoSmithKline (GSK) and any other HIV drug developer anywhere n the world that we might have omitted mentioning.
These firms will continue to offer HIV treatments for years to come and will continue to improve on them. Gilead sciences is the leader of the HIV innovative drugs. Its protease inhibitors and combination drugs have caused a tremendous transformation in HIV victims’ lives and well being.
In related news, a week ago, the U.S. decided upon a new AIDS policy that aim at finding new ways to educate people about HIV. The policy aims also at getting more patients to treatment as fast as possible, urging the FDA to consider reviewing new HIV tests a priority. The guidelines focus on prevention and on making sure that the patients have access to care and to tests that monitor the infection so they can take their drugs at the right time.
This news is good news for HIV victims and for HIV drug developers. More...