Scientists at the US Food and Drug Administration (FDA) working with colleagues in Brazil and India, have shown that genetically modified, non-virulent experimental vaccine against visceral leishmaniasis triggers a stronger immune system response in dogs than does the currently used commercially available canine vaccine. The vaccine is based on the Leishmania parasite, the single-celled organism that causes the disease.
Visceral leishmaniasis is a tropical disease in humans caused by a single-celled parasite called Leishmania donovani, which causes about 500,000 infections and 50,000 deaths each year. A similar species of this parasite, Leishmania infantum, infects dogs. The parasite enters the body through the bite of a particular flea and spends part of its life growing inside a type of immune system cell called a macrophage. Then it escapes from the cell and continues to spread throughout the body.
The study’s finding that an experimental vaccine triggers a stronger immune response in dogs than the commercial one is important because dogs are a major source of human infections in tropical areas. Dogs also occasionally spread the disease in Northern Europe, the United States, and Canada. Drug treatment usually fails to cure infections in dogs and remaining parasites tend to grow resistant to drug treatment. Dogs can then pass on these drug-resistant parasites to humans.
The FDA scientists compared the immunogenicity (ability to trigger immune responses) of the commercial vaccine (Leishmune®) in dogs with that of an experimental vaccine made from genetically modified and weakened live L. donovani parasites that lacked a critical gene called LdCen. Parasites lacking this gene (i.e., LdCen-/- parasites), cannot grow and reproduce inside the macrophage, and eventually die.
Dogs vaccinated with the LdCen-/- parasites had a stronger immune response than those receiving the commercial vaccine. Specifically, their immune system produced more anti bodies and immune system cells called lymphocytes. There was also increased production of certain key chemical signals released by lymphocytes that help stimulate the immune response.
Overall, the findings of FDA scientists demonstrated the potential of the LdCen-/- parasite as a canine vaccine against visceral leishmaniasis and suggest that it is a good candidate for further evaluation to demonstrate its safety and effectiveness.
The FDA scientists are in the Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review.
“Induction of immunogenicity by live attenuated Leishmania donovani centrin deleted parasites in dogs”
Vaccine Available online 8 February 2013
Jacqueline Araújo Fiuzaa,b,c, Helton da Costa Santiagod, Angamuthu Selvapandiyane, Sreenivas Gannavaramc, Natasha Delaqua Riccib, Lilian Lacerda Buenob, Daniella Castanheira Bartholomeub, Rodrigo Correa-Oliveiraa, Hira L. Nakhasic, Ricardo Toshio Fujiwaraa,b,*
a Laboratory of Cellular and Molecular Immunology, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil
b Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
c Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
d Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
e Institute of Molecular Medicine, 254 Okhla Industrial Estate, Phase III, New Delhi 110020, India