Optimization of rabies (Rhabdoviridae: Lyssavirus) dog vaccination schedule using a mathematical model

Abstract

Most cases of human rabies are caused by dog (Canis lupus familiaris) bites. Therefore, the implementation of vaccination programs of these animals is one of the urgent tasks.The work aims to identify the factors influencing the production of antirabies virus-neutralizing antibodies (VNAs) in vaccinated dogs, and to formulate recommendations for adjusting the vaccination schedule using mathematical modeling (MM). We used a fixed-effects modeling procedure to estimate the two-compartment model parameters using log-transformed data (obtained by RFFIT, rapid fluorescent focus inhibition test; and FAVN, fluorescent antibody virus-neutralization test) on the VNAs levels in the serum of vaccinated dogs. More vigorous immune response after a two-dose primary vaccination is formed in juvenile dogs at the age of 3 months to 1 year compared to the adult dogs. Following the primary vaccination and revaccination 1 year after, VNAs were produced more intensively in adult stray dogs than in domestic dogs. The short-term immune response observed in dogs aged up to 3 months is due to the presence of colostral antibodies and the active growth of the organism at this age. The results of our study confirm that most of the dogs have a level of antirabies VNAs of ≥0.5 IU/ml up to two or more years following immunization. However, only regular annual revaccination ensures the protective VNAs level in animals that responded poorly to vaccination due to various factors. The following antirabies vaccination schedule is recommended: primary vaccination of the dog at the age of 3 months up to 1 year with 1-2 month intervals, then revaccination annually. This work also demonstrates the possibility of a wider application of MM methods for solving problems of vaccine prevention.