Rabies is an important public health problem in South East Asia, with cases in this part of the world contributing to about 70% of the global burden. A large number of rabies cases occur in India, however, there is no organized system of surveillance and hence there is a lack of reliable data. Moreover, comprehensive molecular epidemiological studies have not been performed on Indian virus isolates. In this study, we determined the complete nucleotide and deduced amino acid sequence of a primary isolate of rabies virus obtained from the brain of an infected patient. Comparison of the genomic sequence with those of the ten fully sequenced rabies strains available in GenBank showed nucleotide homology ranging from 97% with AY956319 to 81% with AY705373. Amino acid homology of nucleoprotein ranged from 99.7% with AY352493 to 92% with DQ875051. In case of the glycoprotein gene, the homology ranged from 98.8% with AY956319 to 87.2 % with AY705373. An extensive nucleoprotein, glycoprotein, and full-length genome-based phylogenetic analysis was performed along with sequences available from the GenBank. Phylogenetic analysis of the complete genome sequence indicated that this isolate exhibited close homology with the ex Indian strain AY956319.

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.

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.

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