Bangalore: The 25-year-long hunt for an HIV vaccine, an effective jab that could finally nail the mutating virus that infects 2.7 million people every year, may have found a fresh lease of life. Scientists have discovered two potent human antibodies that can stop at least 90% of known global HIV strains from infecting people, and they have also demonstrated, for the first time, the prowess of these disease-fighting proteins over the virus.
In Friday’s issue of the journal?Science, two research teams from the US National Institutes of Health say these antibodies can not only be used to design improved vaccines for HIV prevention, but could be further developed for better drugs for HIV treatment, even along with existing antiviral drugs.
“This is really exciting. While strains maintained in the lab for long can be neutralized easily by most of the neutralizing antibodies developed earlier, these new antibodies neutralize strains directly from the patient, and also of various HIV sub-types,” said R.S. Paranjape, director, National AIDS Research Institute in Pune.
Antibodies, natural molecular watchdogs, are specialized proteins produced by the immune system to fight any foreign particle or micro-organism that enters the body. A handful of antibodies for HIV have been identified lately but none neutralized the virus to this extent, and at such low concentrations. This implies that, if at all used for vaccines, these antibodies would need to be produced in very small quantities.
“Together, these advances teach us that the human immune system is able to make potent antibodies against HIV, and one major goal of HIV vaccination is to teach the immune system to make such antibodies in order to prevent HIV infections from occurring,” said lead authors John R. Mascola and Gary J. Nabel in an email.
Besides their exceptional neutralizing capacity, the new antibodies point to a sort of breakthrough as scientists have also been able to study their structure at the atomic level, revealing a new angle of attack that vaccine designers can exploit. One of the promising targets in the vaccine quest is a spot called the CD4 binding site, or a viral spike, which the virus uses to enter the immune cells. This spot has long known to be the virus’ vulnerability as it doesn’t change with genetic mutation. It’s even been an area of high priority for researchers, but has so far proved difficult to target with antibodies.
With the new findings, say researchers, it will be possible to design a vaccine candidate with the specific shape and size that would bind with the viral spike and stop infection.
“We are currently designing proteins that react strongly with this antibody and will advance them into testing as quickly as possible,” said Mascola and Nabel, though they anticipate it will likely take three to five years to move such a vaccine to clinical trials.
Some experts, though enthused, are keeping their expectations grounded. The study does demonstrate the mechanism of neutralization as well as barriers for eliciting such antibodies but it’s too early to say how they will behave against various HIV strains in human trials, said Sunit K. Singh, a scientist at Hyderabad’s Centre for Cellular and Molecular Biology. Singh specializes in infectious diseases.
AIDS vaccine development has proved to be harder than scientists’ initial estimates, particularly because the virus evades the human immune system differently in different parts of the world. After scores of vaccine trials were unsuccessful, scientists had a glimmer of hope in 2009 when a late stage trial in Thailand showed that the vaccine could cut HIV infection by 31%. An early stage trial in Chennai in India in 2008 showed similar results, but arriving at a consensus on the right strategy for a vaccine isn’t easy.
“These new findings and the studies done on PG9 and PG16 (two other recently identified antibodies) are fuelling a long overdue, if cautious, sense of optimism among scientists involved in AIDS vaccine design and development,” said Rajat Goyal, country director, India, International AIDS Vaccine Initiative. “Many researchers believe that after many years of disappointment their field has finally reached something of a tipping point, and with good reason.”