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Priming immunization determines T helper cytokine mRNA expression patterns in lungs of mice challenged with respiratory syncytial virus.
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1993
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Respiratory Virus ImmunityInflammatory Lung DiseaseRsv Vaccine DevelopmentLung InflammationViral PathogenesisImmunologyImmunotherapyVaccine TargetRespiratory InfectionRsv InfectionMucosal VaccinationVaccine DevelopmentAllergyRsv ChallengeVirologyRespiratory Syncytial VirusVaccinationAntiviral ResponseInfectious Respiratory DiseaseVirus-host InteractionVaccine DesignMedicineViral Immunity
Previous infant trials with formalin‑inactivated alum‑precipitated RSV vaccine failed to protect and were linked to severe disease, whereas live‑attenuated RSV trials showed no vaccine‑enhanced illness. The study aims to define the mechanism underlying vaccine‑enhanced illness in RSV to guide vaccine development. Using a mouse model, the authors measured cytokine mRNA expression in lung tissue by 32P‑labeled oligonucleotide probes in Northern blots of polyA RNA from mice primed with different vaccine preparations and subsequently challenged nasally with live RSV. Priming with inactivated virus or subunit F induced a Th2‑like cytokine mRNA profile (↑IL‑4), whereas priming with live RSV induced a Th1‑like profile (↓IL‑4 relative to IFN‑γ), showing that vaccine formulation and delivery route shape lung cytokine responses upon RSV challenge.
Defining the mechanism for the vaccine-enhanced illness associated with respiratory syncytial virus (RSV) is critical for advancing RSV vaccine development. Previous studies in which infants were vaccinated with formalin-inactivated alum-precipitated whole virus did not protect from RSV infection, and those infected had a high incidence of severe illness. In contrast, previous clinical trials evaluating live attenuated RSV showed no associated vaccine-enhanced illness. We have used a mouse model to explore the immunopathogenesis of RSV infection. In this study cytokine mRNA expression was examined using 32P-labeled oligonucleotide probes in Northern blot analyses of polyA RNA extracted from lungs of mice primed with various vaccine preparations then challenged nasally with live RSV. We have shown that upon challenge, priming of mice with inactivated virus or subunit F glycoprotein induced a pattern of cytokine mRNA expression suggesting a dominant Th2-like lymphocyte response (relative increase in IL-4 mRNA expression). In contrast, challenge of mice primed with live RSV by parenteral or mucosal routes induced a Th1-like pattern of cytokine mRNA expression (relative decrease in IL-4 mRNA expression compared to IFN-gamma mRNA expression). Thus, the formulation and route of delivery of vaccine products can influence the pattern of cytokine expression in lung upon RSV challenge.