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Neonates mount robust and protective adult-like CD8(+)-T-cell responses to DNA vaccines
Jie Zhang1, Nicole Silvestri, J Lindsay Whitton
1The Scripps Research Institute, La Jolla, California 92037, USA.
Insights
Neonates can mount rapid CD8(+) T cell responses after DNA vaccination, challenging the notion of neonatal immunodeficiency. This suggests DNA vaccines can provide early, effective cell-mediated antiviral immunity.
Area of Science:
- Immunology
- Vaccinology
- Neonatal Health
Background:
- Neonates are traditionally considered to have weaker adaptive immune responses, leading to delayed vaccination schedules.
- Current DNA vaccine studies often measure immune responses weeks or months post-vaccination, questioning early priming efficacy.
Purpose of the Study:
- To investigate the rapid induction of immune responses following DNA vaccination in neonates.
- To compare neonatal and adult CD8(+) T cell functions and protective immunity.
Main Methods:
- DNA vaccination administered at birth.
- Analysis of antigen-specific CD8(+) T cell induction and effector functions.
- Assessment of protective immunity against lymphocytic choriomeningitis virus.
Main Results:
- DNA vaccination at birth rapidly induces antigen-specific CD8(+) T cells in neonates.
- Neonatal and adult CD8(+) T cells exhibit similar cytokine production and antigen avidity.
- Rapid protective immunity mediated by CD8(+) cytotoxic T cells is acquired neonatally.
Conclusions:
- Neonates possess robust CD8(+) T cell responses, contradicting assumptions of significant neonatal immunodeficiency.
- DNA vaccines show potential for safe and effective early-life administration to confer cell-mediated antiviral immunity.
Abstract:
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.