Neonates Mount Robust and Protective Adult-Like CD8+-T-Cell Responses to DNA Vaccines

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http://jvi.asm.org/cgi/content/abstract/76/23/11911

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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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Neonates Mount Robust and Protective Adult-Like CD8+-T-Cell Responses to DNA Vaccines

Neonates Mount Robust and Protective Adult-Like CD8⁺-T-Cell Responses to DNA Vaccines