CD4-independent protective cytotoxic T cells induced in early life by a non-replicative delivery system based on virus-like particles

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)-γ 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. © 2003 Elsevier Science (USA).