CD4-independent protective cytotoxic T cells induced in early life by a non-replicative delivery system based on virus-like particles.
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.
Martinez
Xavier
X
W.H.O. Collaborating Center for Neonatal Vaccinology, Department of Pathology, University of Geneva Medical School, Switzerland.
Regner
Matthias
M
Kovarik
Jiri
J
Zarei
Shohreh
S
Hauser
Conrad
C
Lambert
Paul-Henri
PH
Leclerc
Claude
C
Siegrist
Claire-Anne
CA
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D015704:CD4 Antigens / Q000502:physiology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology*
D015704:CD4 Antigens; D014765:Viral Vaccines; D007371:Interferon-gamma