Roles of the Fc Receptor γ-Chain in Inducing Protective Immune Responses after Heterologous Vaccination against Respiratory Syncytial Virus Infection.

Hye Suk Hwang,Kap Seung Yang,Hoonsung Cho,Young-Tae Lee,Ki-Hye Kim,Sang-Moo Kang,Ho Seong Seo

doi:10.3390/vaccines9030232

Abstract

The roles of the Fc receptor (FcR) in protection or inflammatory disease after respiratory syncytial virus (RSV) vaccination and infection remain unknown. Virus-like particles containing RSV fusion proteins (RSV F-VLPs) induce T-helper type 1 antibody responses and protection against RSV. Heterologous RSV F-VLP prime and formalin-inactivated RSV (FI-RSV) boost vaccination has been reported to be effective in providing protection without inflammatory disease. Here, we investigated whether the FcRγ-chain is important for immune protection by the heterologous F-VLP and FI-RSV vaccination using FcRγ-chain knockout (−/−) mice. RSV F-VLP-primed and FI-RSV-boosted FcRγ −/− mice displayed less protective efficacy, as shown by higher lung viral titers upon RSV challenge, compared to RSV F-VLP-primed and FI-RSV-boosted immunized wild-type mice. RSV F-VLP and FI-RSV immunization induced lower levels of neutralizing activity and interferon-γ-producing CD8 T-cells in the bronchoalveolar lavage cells of FcRγ −/− mice than in those of wild-type mice. In addition, FcRγ −/− mice displayed a trend of enhancing lung histopathology after RSV vaccination and infection. This study suggests that the FcRγ-chain plays an important role in inducing antiviral protection and CD8 T-cell responses in RSV F-VLP prime and FI-RSV boost vaccination after RSV infections.

Highlights

Respiratory syncytial virus (RSV) is a pathogen that is the leading cause of severe respiratory disease in infants, children, and the elderly
We reported that heterologous respiratory syncytial virus (RSV) F-Virus-like particles (VLPs) prim and Formalin-inactivated RSV (FI-RSV) boost vaccination was effective in providing protection while preventing enhanced respiratory and inflammatory disease after RSV infection, compared to the FI-RSV vaccination only [25]
To evaluate the possible roles of FcRγ in inducing protective immune responses to To evaluate the possible roles of FcRγ in inducing protective immune responses to RSV, the groups of WT and FcRγ −/− mice were intramuscularly immunized via a heterRSV, the groups of WT and FcRγ −/− mice were intramuscularly immunized via a hetologous F-VLP prime and FI-RSV boost regimen

Summary

Introduction

Respiratory syncytial virus (RSV) is a pathogen that is the leading cause of severe respiratory disease in infants, children, and the elderly. Formalin-inactivated RSV (FI-RSV) vaccines have failed because of vaccine-enhanced respiratory disease (ERD) in young vaccinee children after exposure to RSV infection during the following epidemic season [1,2]. Virus-like particles (VLPs) are a unique delivery platform for virus structural proteins, mimicking viral morphology without genetic materials, and their advantages lie in their safety, immunogenicity, and antigen stability [3]. VLP vaccine platforms have been reported to avoid ERD in preclinical studies. VLP-based RSV vaccines assemble with the human metapneumovirus (hMPV)

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