Combining DNA and protein vaccines for early life immunization against respiratory syncytial virus in mice
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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
1W.H.O. Collaborating Center for Neonatal Vaccinology Departments of Pathology and Pediatrics, University of Geneva Medical School, Geneva, Switzerland.
Insights
Early life immunization with respiratory syncytial virus (RSV)-F DNA and protein vaccines shows distinct immune responses. Sequential or combined strategies enhance antibody and cytotoxic T lymphocyte responses, offering promising approaches for infant immunization.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Neonatal immunization is crucial for protecting infants from infectious diseases like respiratory syncytial virus (RSV).
- Understanding early-life immune responses to different vaccine platforms is essential for developing effective infant vaccines.
Purpose of the Study:
- To investigate the immune responses to RSV-F DNA and RSV-F protein immunization in neonatal murine models.
- To compare the efficacy of sequential and combined DNA/protein immunization strategies in early life.
Main Methods:
- Murine models of neonatal immunization were used to assess responses to RSV-F DNA and protein.
- Antibody (Ab), interferon-gamma (IFN-gamma), and cytotoxic T lymphocyte (CTL) responses were measured.
- Interleukin-5 (IL-5) production was analyzed to evaluate T helper cell responses.
Main Results:
- RSV-F DNA induced comparable Ab, IFN-gamma, and CTL responses in young and adult mice.
- RSV-F protein elicited significantly higher IL-5 responses in early life.
- Sequential DNA priming/protein boosting enhanced Ab and CTL responses while reducing IL-5.
- Combined DNA/protein immunization induced early Ab, preferential IL-5, and strong CTL responses.
Conclusions:
- Both sequential and combined DNA/protein immunization strategies show potential for early-life RSV vaccination.
- Tailoring vaccine sequences and combinations can modulate immune responses for improved infant protection against RSV.
Abstract:
Early life responses to respiratory syncytial virus (RSV)-F DNA and RSV-F protein immunization were studied in murine models of neonatal immunization. RSV-F DNA induced similar antibody (Ab) responses, antigen-specific IFN-gamma production and cytotoxic T lymphocyte (CTL) responses in 1-week-old and adult BALB / c mice. In contrast, RSV-F protein induced much higher IL-5 responses in early life. Both vaccines elicited Ab and CTL responses in spite of maternal Ab, but with distinctive kinetics. Sequential RSV-F DNA priming / protein boosting primed 1-week-old mice for RSV-F-specific CTL responses, reduced IL-5 production and enhanced Ab responses. In contrast, IL-5 exceeded IFN-gamma responses when young mice were primed with protein and boosted with DNA. Last, when protein and DNA immunization were combined, a single vaccine dose induced early Ab responses, preferential IL-5 responses but strong CTL responses. Sequential or combined DNA / protein immunization thus represent interesting strategies for early life immunization.
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