TEM micrograph with numerous rabies virions (small, dark grey, rodlike particles) and Negri bodies (the larger pathognomonic cellular inclusions of rabies infection). © CDC/Dr Fred Murphy
The recently completed trial in India showed that the new monoclonal antibody (RAB-1) therapy resulted in protective antibody levels in the serum of treated subjects equal to the current standard of treatment, which is often not available in the areas of the world hit hardest by rabies.
Details of the study were reported at the American Society for Microbiology's 50th annual Interscience Conference on Antimicrobial Agents and Chemotherapy meeting in Boston.
"We are very encouraged by the results from this trial," said Dr Donna Ambrosino, executive director of MassBiologics and a professor of pediatrics at the university's medical school.
The World Health Organisation estimates more than 10 million people are exposed to rabid animals each year, resulting in more than 55,000 deaths. About 95 per cent of human deaths from rabies occur in Asia and Africa.
Untreated, the virus causes acute brain swelling that is fatal once symptoms appear. However, the infection is preventable by prompt treatment after exposure, involving administration of a rabies vaccine and rabies immune globulin (RIG) soon after exposure.
While the vaccine is often available, the preferred human rabies immune globulin (HRIG), which is derived from human blood, is expensive material and typically not available in developing countries.
As an alternative to HRIG, equine immune globulin derived from horse serum is used in many parts of the world, but it is also scarce, expensive and can carry significant side effects.
Too frequently, however, there is neither HRIG nor equine product available to treat all those in the developing world who are bitten by rabid animals.
Subhash Kapre, of the Serum Institute of India, said high hopes were held for the new therapy, and the next step for clinical studies was already in the planning.
The new therapy could be used in place of HRIG. Pre-clinical testing showed that it neutralised all isolates available from a panel of rabies viruses.
MassBiologics then partnered with the Serum Institute of India, which is one of the world's largest manufacturers of vaccines, including a major supplier of the rabies vaccine, to develop the capacity to produce monoclonal antibodies in India, and advance RAB-1 into clinical trials.
In the Phase 1 trial in India, 74 healthy volunteers were randomised into several groups that either received escalating doses of RAB-1 or of HRIG combined with vaccine.
The RAB-1 was well tolerated by all subjects. Blood samples were analysed and showed the volunteers who received RAB-1 and vaccine at a dose of 0.150 mg/kg had levels of rabies antibodies equal to or higher than the levels from those volunteers who had received the standard does of HRIG and vaccine.
The half-life of RAB-1 was 18-19 days. Blood samples were also analysed by the Kansas State Veterinary Diagnostic Laboratory to determine if antibodies present in the volunteers' bloodstream could neutralise rabies virus in a cell-based assay using two different strains of virus.
That data showed that volunteers who received RAB-1 at 0.150 mg/kg with vaccine had similar or better protective serum levels when compared to those who received HRIG with vaccine.
Following the successful conclusion of this Phase 1 trial, the Serum Institute of India and MassBiologics are moving ahead in a clinical trial in India to evaluate the effectiveness of RAB-1 combined with vaccine compared to the standard of care for patients who have been exposed to potentially rabid animals.
"Monoclonal antibodies can be produced in large quantities and at much lower costs than blood products, which could make this new therapy broadly available in Asia and India," Dr Kapre said.
"We remain optimistic that this programme will eventually prevent thousands of deaths from rabies each year."