Neonates mount robust and protective adult-like CD8(+)-T-cell responses to DNA vaccines.
Neonates are thought to mount less vigorous adaptive immune responses than adults to antigens and infectious agents. This concept has led to a delay in the administration of many currently available vaccines until late infancy or early childhood. It has recently been shown that vaccines composed of plasmid DNA can induce both humoral and cell-mediated antimicrobial immunity when administered within hours of birth. In most of these studies, immune responses were measured weeks or months after the initial vaccination, and it is therefore questionable whether the observed responses were actually the result of priming of splenocytes within the neonatal period. Here we show that DNA vaccination at birth results in the rapid induction of antigen-specific CD8(+) T cells within neonatal life. Analyses of T-cell effector functions critical for the resolution of many viral infections revealed that neonatal and adult CD8(+) T cells produce similar arrays of cytokines. Furthermore, the avidities of neonatal and adult CD8(+) T cells for peptide and the rapidity with which they upregulate cytokine production after recall encounters with antigen are similar. Protective immunity against the arenavirus lymphocytic choriomeningitis virus, which is mediated by CD8(+) cytotoxic T cells, is also rapidly acquired within the neonatal period. Collectively these data imply that, at least in the case of CD8(+) T cells, neonates are not as immunodeficient as previously supposed and that DNA vaccines may be an effective and safe means of providing critical cell-mediated antiviral immunity extremely early in life.
Zhang
Jie
J
The Scripps Research Institute, La Jolla, California 92037, USA.
Silvestri
Nicole
N
Whitton
J Lindsay
JL
Hassett
Daniel E
DE
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control
D000956:Antigens, Viral; D016207:Cytokines; D009698:Nucleoproteins; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma