Protective Th1 immune responses against chronic toxoplasmosis induced by a protein–protein vaccine combination but not by its DNA–protein counterpart

• Published in: Vaccine 2008-09, Vol.26 (41), p.5289-5295
• Main Authors: Jongert, E, Verhelst, D, Abady, M, Petersen, E, Gargano, N
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibodies, Protozoan - biosynthesis; Antibodies, Protozoan - immunology; Antibody Formation - immunology; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Antigens, Protozoan - pharmacology; Applied microbiology; Biological and medical sciences; Cysts; Deoxyribonucleic acid; DNA; Enzyme-Linked Immunosorbent Assay; Ethanol; Female; Fundamental and applied biological sciences. Psychology; Heterologous vaccine; Human protozoal diseases; Immune response; Immune system; Immunity, Cellular - immunology; Infections; Infectious diseases; Lymphocyte Activation; Medical sciences; Mice; Microbiology; Parasites; Parasitic diseases; Proteins; Protozoal diseases; Protozoan Vaccines - genetics; Protozoan Vaccines - immunology; Th1 Cells - immunology; Th1/Th2; Toxoplasma - genetics; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis; Toxoplasmosis - immunology; Toxoplasmosis - parasitology; Toxoplasmosis - prevention & control; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - genetics; Vaccines, DNA - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.07.032

Abstract Vaccine-induced protection against toxoplasmosis is correlated with cellular immune responses to Toxoplasma gondii , both in animals and man. The goal of the current study was to evaluate whether the combination of a recombinant protein and a plasmid DNA vaccine could offer an advantage over the protein mixture, and protect outbred mice against infection with T. gondii . To this purpose, the chimeric protein rEC2, encoding antigenic fragments of surface-associated proteins MIC2, MIC3 and SAG1, was combined with pGRA7 plasmid DNA or rGRA7 protein. High levels of antibodies were elicited by both vaccine formulations. The protein–DNA vaccine elicited a polarized Th1/Th2 immune response, characterized by IFN-γ and IL-10, and afforded low protection (24%) against brain cyst formation. In contrast, the protein–protein vaccine elicited a Th1-focused immune response, characterized by IFN-γ and IL-2 production, conferring a strong protection (79%) against brain cyst formation in chronic toxoplasmosis. We show here that GERBU adjuvanted protein vaccines confer better protection against toxoplasmosis than the protein–DNA heterologous vaccine.