Heterologous priming-boosting with DNA and modified vaccinia virus Ankara expressing tryparedoxin peroxidase promotes long-term memory against Leishmania major in susceptible BALB/c Mice.

Abstract

Leishmaniasis affects 12 million people, but there are no vaccines in routine clinical use. Th1 polarizing vaccines that elicit long-term protection are required to prevent disease in susceptible populations. We recently showed that heterologous priming-boosting with tryparedoxin peroxidase (TRYP) DNA followed by TRYP-modified vaccinia virus Ankara (TRYP MVA) protected susceptible BALB/c mice from Leishmania major. Here we compared treatment with TRYP DNA with treatment with TRYP DNA/TRYP MVA. We found that equivalent levels of protection during the postvaccination effector phase correlated with equivalent levels of serum immunoglobulin G2a and gamma interferon (IFN-gamma) in draining lymph nodes. In contrast, challenge infection during the memory phase revealed that there was enhanced clinical efficacy with TRYP DNA/TRYP MVA. This correlated with higher levels of effector phase splenic IFN-gamma, sustained prechallenge levels of memory phase IFN-gamma, and a more polarized post-L. major challenge Th1 response compared to the Th2/T(reg) response. Thus, TRYP DNA/TRYP MVA, but not TRYP DNA alone, provides long-term protection against murine leishmaniasis.

• Authors: Carmel B Stober, Uta G Lange, Mark T M Roberts, Antonio Alcami, Jenefer M Blackwell
• Journal: Infection and immunity (Infect Immun) Vol. 75 Issue 2 Pg. 852-60 (Feb 2007) ISSN: 0019-9567 [Print] United States
• PMID: 17101647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Protozoan
• Immunoglobulin G
• Protozoan Proteins
• Protozoan Vaccines
• Vaccines, DNA
• Interferon-gamma
• Peroxidases
• tryparedoxin peroxidase

Topics

• Animals
• Antibodies, Protozoan (blood)
• Cells, Cultured
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Foot (pathology)
• Immunization, Secondary
• Immunoglobulin G (blood)
• Immunologic Memory
• Interferon-gamma (biosynthesis)
• Leishmania major (immunology)
• Leishmaniasis, Cutaneous (immunology, prevention & control)
• Lymph Nodes (immunology)
• Lymphocytes (immunology)
• Mice
• Mice, Inbred BALB C
• Peroxidases (genetics, immunology)
• Protozoan Proteins (genetics, immunology)
• Protozoan Vaccines (administration & dosage, genetics, immunology)
• Vaccines, DNA (administration & dosage, genetics, immunology)
• Vaccinia virus (genetics)