But do they Protect?
The numerous discoveries of potent broadly neutralizing antibodies against HIV that have occurred in the last two years suggest that the human immune system is capable of making such antibodies against the virus more routinely than originally thought. This has made researchers more optimistic about the possibility of inducing antibodies that are capable of neutralizing a wide array of HIV strains at low concentrations. However, whether or not these antibodies, if induced by a vaccine, will actually protect humans against HIV infection is still an open question. And because there are no vaccine candidates yet that can induce these broadly neutralizing antibodies, researchers are instead planning to evaluate the protective efficacy of these antibodies in passive immunization studies.
Yesterday at AIDS Vaccine 2011, Barney Graham of the Vaccine Research Center (VRC) at the US National Institute of Allergy and Infectious Diseases presented the VRC’s plans to test one of their broadly neutralizing antibodies known as VRC01 in passive immunization trials in both adults and infants as a test of concept to see if this antibody can block HIV infection. Graham said the passive immunotherapy studies would allow researchers to define the specificity, potency, and function of antibodies to provide targets for vaccine-induced protection.
The VRC is planning to conduct a series of Phase I passive immunizations studies with VRC01. The first, which is slated to begin in December, will test the safety and pharmacokinetics of administering VRC01 to HIV-infected and uninfected adults in the US. Another Phase I study to test the safety and pharmacokinetics of VRC01 passive immunization will also be conducted in infants in the US. Following this, researchers will conduct a safety study in infants in developing countries. Finally, the VRC plans to conduct a Phase IIb study, which is scheduled to start in mid-2013, in infants to see if administration of the antibody to infants can protect against infection.
Plans for an additional Phase IIb study in HIV uninfected adults are on hold for now, although Graham said this would be the most informative trial for vaccine-related protection by VRC01. "The problem is in manufacturing," said Graham. Conducting a Phase IIb study in adults requires a large quantity of antibody be produced. To conduct the three Phase I trials (one in adults and two in infants) and a Phase IIb trial in infants, only 3 kg of VRC01 is required. Whereas to conduct a single Phase IIb study in adults, 30kg of the antibody would need to be manufactured.
Data from a passive transfer study in non-human primates indicate that a lower dose of VRC01 only protects 50% animals against simian immunodeficiency virus infection, while at a higher dose all of the animals are protected. so researchers at the VRC are currently exploring several ways of engineering the VRC01 antibody to make it more effective at lower doses. Some of the approaches they are pursuing include improving the Fc receptor function of the antibody or increasing its half life. Researchers are also trying to improve the manufacturing process.