A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis.

Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human.

Investigation of protective level of rabies antibodies in vaccinated dogs in Chennai, India.

BACKGROUND: Rabies is still endemic in India causing an estimated 20,000 human deaths a year. Free roaming dogs and unvaccinated owned dogs play a major role in the maintenance of the disease. Dog vaccination is the most crucial aspect of rabies prevention and control strategies; therefore vaccine immunogenicity and longevity are important determinants of the efficiency of rabies control efforts. METHODS: In this study at Madras Veterinary College, India, a total of 297 serum samples were collected from owned dogs that were vaccinated against rabies. Data regarding age, gender, breed, neuter status and last date of vaccination were collected at the time of blood collection. The level of rabies virus neutralising antibodies in the sera of these dogs was measured through rapid focus fluorescence inhibition test. The factors associated with protective level of rabies antibodies in vaccinated dogs were investigated through multivariable regression analysis. RESULTS: This cross-sectional investigation shows that only 40% (119/297) of the all the dogs in the study showed presence of protective level of anti-rabies antibodies, and 40% (72/180) of the dogs vaccinated within the last year showed presence of protective levels of antibodies causing concern about rabies vaccine quality and its impact on rabies control. The study also shows that older and neutered dogs are more likely to have protective titre among vaccinated dogs, while non-descript breed dogs are less likely to have a protective titre compared to pure breeds. CONCLUSION: In this study 60% (108/180) of young prima dogs and adult dogs did not show protective levels of antibodies within the year of last rabies vaccination, although they had previous vaccination history. This high percentage of apparent non-responders is a cause of concern of administration, distribution, storage, potency and quality management of vaccines in India.

N-methylisatin-beta-thiosemicarbazone derivative (SCH 16) is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo.

BACKGROUND: During the early and mid part of 20th century, several reports described the therapeutic effects of N-methylisatin-beta-Thiosemicarbazone (MIBT) against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV), Dengue-2 (Den-2) and West Nile viruses (WNV). RESULTS: Amongst the fourteen Mannich bases of MIBT derivatives tested one compound - SCH 16 was able to completely inhibit in vitro Japanese encephalitis virus (JEV) and West Nile virus (WNV) replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC50) produced by JEV and WNV at a concentration of 16 microgm/ml (0.000025 microM) and 4 microgm/ml (0.000006 microM) respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100%) prevent mortality in mice challenged with 50LD50 JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation. CONCLUSION: Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection in vitro. SCH 16 was also found to completely inhibit JEV replication in vivo in a mouse model challenged peripherally with 50LD50 of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent.