Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice.

Abstract

Lyme disease, due to infection with the tick-borne spirochete Borrelia burgdorferi, is a multisystem disorder that can lead to chronic disabling symptoms. Abs to the outer surface protein A (OspA) of B. burgdorferi provide protection against infection, and OspA is now the basis of a first generation recombinant vaccine undergoing phase III efficacy studies. Recent studies have suggested that T cells reactive with N-terminal epitopes in OspA could contribute to the development of treatment-resistant Lyme arthritis. In the present studies, we use the murine model of Lyme borreliosis to define an OspA T cell epitope located in the carboxyl terminus that accelerates anti-OspA IgG production after infection. In addition, we show that this T cell epitope is elicited by immunization with rOspA or with a truncated form of OspA that contains the B cell epitope targeted by protective OspA mAb. Polyclonal antisera to the truncated OspA fragment can protect mice from challenge infection. These results are the first demonstration of a B. burgdorferi-specific peptide that elicits a biologically important T cell response in vivo and have implications for the design of a second generation OspA-based subunit vaccine.

• Authors: L K Bockenstedt, E Fikrig, S W Barthold, R A Flavell, F S Kantor
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 157 Issue 12 Pg. 5496-502 (Dec 15 1996) ISSN: 0022-1767 [Print] United States
• PMID: 8955199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Antigens, Surface
• Bacterial Outer Membrane Proteins
• Bacterial Vaccines
• Immunoglobulin G
• Lipoproteins
• OspA protein
• Peptides
• Vaccines, Synthetic
• Interleukin-4

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Bacterial (biosynthesis)
• Antigens, Bacterial (immunology)
• Antigens, Surface (immunology)
• Bacterial Outer Membrane Proteins (immunology)
• Bacterial Vaccines (immunology)
• Epitope Mapping
• Female
• Immunization, Passive
• Immunoglobulin G (immunology)
• Interleukin-4 (biosynthesis)
• Lipoproteins
• Lymphocyte Activation
• Mice
• Mice, Inbred C3H
• Molecular Sequence Data
• Peptides (immunology)
• T-Lymphocytes (immunology)
• Vaccines, Synthetic (immunology)