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Lipopolysaccharide Inhibits FI-RSV Vaccine-enhanced Inflammation Through Regulating Th Responses

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Summary

Respiratory syncytial virus (RSV) infection is the primary cause of respiratory disease in infants. The formalin-inactivated RSV (FI-RSV) vaccine resulted in an enhanced respiratory disease (ERD) in infants upon natural RSV infection, which is a major obstacle for development of safe and efficacious vaccines. Excessive and uncontrolled Th immune responses could be involved in the ERD. Agonists of TLRs are used as adjuvants to guide the type of immune response induced by vaccines. We evaluated the impact of lipopolysaccharide (LPS), the agonist of TLR4, on ERD as the adjuvant of FI-RSV. The results showed that LPS remarkably inhibited FI-RSV-enhanced lung inflammation, mucus production, airway inflammatory cell infiltration, and inflammatory cytokines following RSV challenge. Interestingly, LPS inhibited both Th2 and Th17 type cytokines in lungs of FI-RSV-immunized mice following RSV challenge, without an increase in the Th1 type cytokines, suggesting a controlled immune response. In contrast, Pam3Cys and Poly(I:C), the agonist of TLR1/2 or TLR3, partly inhibited FI-RSV-enhanced lung inflammation. Pam3Cys inhibited Th17 type cytokine IL-17, but promoted both Th1 and Th2 type cytokines. Poly(I:C) inhibited Th2 and Th17 type cytokines, but promoted Th1 type cytokines. In addition, LPS promoted IgG and IgG2a antibody production, which might provide protection from RSV challenge. These results suggest that LPS inhibits ERD without impairment in antibody production and protection, and the mechanism appears to be related with regulation of Th responses induced by FI-RSV.

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Authors and Affiliations

  1. Department of Immunology, Hebei Medical University, Shijiazhuang, 050017, China

    Wei Yin, Hong-yong Li, Yu-qing Deng, Wen-jian Li, Ying Liu & Rui-hong Zeng

  2. Department of Biology, Cangzhou Medical College, Cangzhou, 061001, China

    Wei Yin & Ying Liu

  3. Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, 050017, China

    Rui-hong Zeng

  4. Basic Medical College, Hebei Medical University, Shijiazhuang, 050017, China

    Bo-yang Zheng

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  1. Wei Yin
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  2. Hong-yong Li
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  3. Bo-yang Zheng
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  4. Yu-qing Deng
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  5. Wen-jian Li
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  7. Rui-hong Zeng
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Correspondence to Rui-hong Zeng.

Additional information

This study was supported by grants from the National Natural Science Foundation of China (No. 81671635 and No. 31240084) and Natural Science Foundation of Hebei Province (No. H2016206473).

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Yin, W., Li, Hy., Zheng, By. et al. Lipopolysaccharide Inhibits FI-RSV Vaccine-enhanced Inflammation Through Regulating Th Responses. CURR MED SCI 39, 363–370 (2019). https://doi.org/10.1007/s11596-019-2044-0

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  • DOI: https://doi.org/10.1007/s11596-019-2044-0

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