Neonates Mount Robust and Protective Adult-Like CD8+-T-Cell
Responses to DNA Vaccines
Jie Zhang, Nicole Silvestri, J. Lindsay Whitton, and Daniel E.
Hassett*
The Scripps Research Institute, La Jolla, California 92037
Received 29 April 2002/ Accepted 27 August 2002
Neonates are thought to mount less vigorous adaptive immuneresponses 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. Ithas
recently been shown that vaccines composed of plasmid DNAcan induce
both humoral and cell-mediated antimicrobial immunitywhen
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 splenocyteswithin
the neonatal period. Here we show that DNA vaccinationat birth
results in the rapid induction of antigen-specificCD8+ T
cells within neonatal life. Analyses of T-cell effectorfunctions
critical for the resolution of many viral infectionsrevealed that
neonatal and adult CD8+ T cells produce similararrays of
cytokines. Furthermore, the avidities of neonataland adult CD8+
T cells for peptide and the rapidity with whichthey upregulate
cytokine production after recall encounterswith antigen are similar.
Protective immunity against the arenaviruslymphocytic
choriomeningitis virus, which is mediated by CD8+ cytotoxic T cells,
is also rapidly acquired within the neonatalperiod. Collectively
these data imply that, at least in thecase of CD8+ T
cells, neonates are not as immunodeficient aspreviously supposed and
that DNA vaccines may be an effectiveand safe means of providing
critical cell-mediated antiviralimmunity extremely early in life.
* Corresponding author. Mailing address: The Scripps Research
Institute CVN-9, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858)
784-7497. Fax: (858) 784-7377. E-mail:
dhassett@scripps.edu.
This is manuscript no. 14962-NP from the Scripps Research Institute.
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