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Published on: June 25, 2015
Combining DNA and protein vaccines for early life immunization against respiratory syncytial virus in mice
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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