Title

Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells

Authors

Ki-Hye Kim, Georgia State University
Young-Tae Lee, Georgia State University
Hye Suk HwangFollow
Young-Man Kwon, Georgia State UniversityFollow
Yu-Jin Jung, Georgia State UniversityFollow
Youri Lee, Georgia State UniversityFollow
Jong Seok LeeFollow
Yu-Na Lee, Georgia State UniversityFollow
Soojin Park, Georgia State University
Sang-Moon Kang, Georgia State UniversityFollow

Document Type

Article

Publication Date

10-2015

Abstract

Respiratory syncytial virus (RSV) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated RSV (FI-RSV) in alum formulation. Here, we investigated alum adjuvant effects on protection and disease after FIRSV immunization with or without alum in comparison with live RSV reinfections. Despite viral clearance, live RSV reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of RSV specific IFN-γ+IL4-, IFN-γ-TNF-α+, IFN-γ+ TNF-α- effector CD4 and CD8 T cells. Alum adjuvant significantly improved protection as evidenced by effective viral clearance compared to unadjuvanted FI-RSV. However, in contrast to unadjuvanted FI-RSV, alum-adjuvanted FI-RSV (FI-RSV-A) induced severe vaccine- enhanced RSV disease including weight loss, eosinophilia, and lung histopathology. Alum adjuvant in the FI-RSV-A was found to be mainly responsible for inducing high levels of RSV-specific IFN-γ-IL4+, IFN-γ-TNF-α+ CD4+ T cells, and proinflammatory cytokines IL-6 and IL-4 as well as B220+ plasmacytoid and CD4+ dendritic cells, and inhibiting the induction of IFN-γ+CD8 T cells. This study suggests that alum adjuvant in FI-RSV vaccines increases immunogenicity and viral clearance but also induces atypical T helper CD4+ T cells and multiple inflammatory dendritic cell subsets responsible for vaccine-enhanced severe RSV disease.

Comments

Originally Published in:

PLoS ONE 10(10): e0139916. https://doi.org/10.1371/journal.pone.0139916

Recommended Citation

Kim K-H, Lee Y-T, Hwang HS, Kwon Y-M, Jung Y-J, Lee Y, et al. (2015) Alum Adjuvant Enhances Protection against Respiratory Syncytial Virus but Exacerbates Pulmonary Inflammation by Modulating Multiple Innate and Adaptive Immune Cells. PLoS ONE 10(10): e0139916. https://doi.org/10.1371/journal.pone.0139916

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This work is licensed under a Creative Commons Attribution 4.0 International License.