The proposed research addresses the public health hazard posed by Nipah virus infection in wildlife and domestic animals. An animal vaccine would be an effective tool both in the United States and abroad, for control and prevention of this deadly emerging infectious disease. Most emerging infectious diseases in humans are zoonoses, in which wildlife serves as the major reservoir for transmission of these agents to domestic animals and humans. Nipah virus is a newly described zoonotic paramyxovirus. Outbreaks of Nipah infection occurred in 1998-1999 in Malaysia and in 2001 and 2003-2004 in Bangladesh, killing more than 135 people and initially generating mortality rates of 40% and recently of more than 69%. The biological properties of Nipah virus allow it to infect multiple species and cause significantly high mortality in humans. Flying foxes (Pteropus bats) have been identified as the probable natural host for Nipah virus. Initial outbreaks of Nipah virus are believed to be caused by contact with pigs infected through the consumption of bat saliva-tainted fruit or bat excrement in pig fodder. Prophylactic immunization may be the most effective solution to control the Nipah virus reservoirs in animals. The objective of this project is to construct and characterize replication-competent and replication-deficient recombinant rabies virus vaccines that express Nipah virus G and F proteins. Live non-pathogenic rabies viruses (RV) represent very safe and efficacious vaccines that can be administered by the oral route. They have already been used successfully as vectors to produce wildlife vaccines against rabies and SARS. While immune responses necessary for protection against Nipah virus infection have not been completely defined, passive transfer of monospecific immune sera against the F and G proteins of Nipah virus protects hamsters against a lethal challenge by this virus, indicating that neutralizing antibodies are probably the major effectors against this viral infection. Because recombinant RVs can replicate in cells of mucosal membranes, these constructs are uniquely suited to induce immunity in wildlife through oral vaccination. We propose to test recombinant vaccines in a mouse model to assess their abilities to induce Nipah virus-neutralizing antibodies.
At present there is no prophylaxis for Nipah virus. Development of immunogenic vaccine constructs represents a step toward effective Nipah vaccines for wildlife and domestic animals that will be useful for control of future disease outbreaks and potential international translocation of the Nipah virus. This project will contribute to the information base needed for the development of future rhabdovirus-based recombinant vaccines against emerging diseases.
