CD4-independent protective cytotoxic T cells induced in early life by a non-replicative delivery system based on virus-like particles |
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Authors: | Martinez Xavier Regner Matthias Kovarik Jiri Zarei Shohreh Hauser Conrad Lambert Paul-Henri Leclerc Claude Siegrist Claire-Anne |
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Institution: | W.H.O. Collaborating Center for Neonatal Vaccinology, Department of Pathology, University of Geneva Medical School, Switzerland. |
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Abstract: | The relative immaturity of the neonatal immune system limits CD4(+) Th1 and cytotoxic T lymphocyte (CTL) responses, and represents a significant challenge for the development of vaccines against intracellular pathogens. In this report, we demonstrate the ability of a non-replicative delivery system based on parvovirus-like particles (VLP) to induce CTL responses in the neonatal period. A single immunization of 1-week-old BALB/c mice with recombinant VLP carrying a CD8(+) T cell determinant from lymphocytic choriomeningitis virus (VLP-LCMV) induced antigen-specific CD8(+) cytotoxic T cells that were similar to those elicited by adult immunization, as assessed by cytotoxic activity, interferon (IFN)-gamma secretion, cytotoxic precursor cell frequencies, in vitro avidity for antigen and protective activity against viral challenge. These CTL responses are elicited within 2 weeks of a single immunization, in the absence of adjuvant and independently of the presence and help of CD4(+) T cells, highlighting the potential of VLP as candidate vaccine vectors in early life. |
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Keywords: | early life neonatal virus-like particles cytotoxic T cells |
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