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Keywords = enhanced RSV disease (ERD)

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19 pages, 323 KiB  
Review
The Development of Animal Models for Respiratory Syncytial Virus (RSV) Infection and Enhanced RSV Disease
by Gengxin Zhang, Binbin Zhao and Jiangning Liu
Viruses 2024, 16(11), 1701; https://doi.org/10.3390/v16111701 - 30 Oct 2024
Cited by 3 | Viewed by 3014
Abstract
The development of immunoprophylactic products against respiratory syncytial virus (RSV) has resulted in notable advancements, leading to an increased demand for preclinical experiments and placing greater demands on animal models. Nevertheless, the field of RSV research continues to face the challenge of a [...] Read more.
The development of immunoprophylactic products against respiratory syncytial virus (RSV) has resulted in notable advancements, leading to an increased demand for preclinical experiments and placing greater demands on animal models. Nevertheless, the field of RSV research continues to face the challenge of a lack of ideal animal models. Despite the demonstration of efficacy in animal studies, numerous RSV vaccine candidates have been unsuccessful in clinical trials, primarily due to the lack of suitable animal models. The most commonly utilized animal models for RSV research are cotton rats, mice, lambs, and non-human primates. These animals have been extensively employed in mechanistic studies and in the development and evaluation of vaccines and therapeutics. However, each model only exemplifies some, but not all, aspects of human RSV disease. The aim of this study was to provide a comprehensive summary of the disease symptoms, viral replication, pathological damage, and enhanced RSV disease (ERD) conditions across different RSV animal models. Furthermore, the advantages and disadvantages of each model are discussed, with the intention of providing a valuable reference for related RSV research. Full article
19 pages, 14377 KiB  
Article
An Optimized FI-RSV Vaccine Effectively Protects Cotton Rats and BALB/c Mice without Causing Enhanced Respiratory Disease
by Min Lin, Wei Zhang, Yi-Fan Yin, Jun-Yu Si, Lu-Jing Zhang, Li Chen, Xue Lin, Ying-Bin Wang, Jun Zhang, Zi-Zheng Zheng and Ning-Shao Xia
Viruses 2022, 14(10), 2085; https://doi.org/10.3390/v14102085 - 20 Sep 2022
Cited by 5 | Viewed by 3912
Abstract
Background: Despite considerable efforts toward vaccine development in past decades, no effective vaccines against respiratory syncytial virus (RSV) are available. Recently, we showed that an optimized formalin concentration can preserve prefusion protein (pre-F) on RSV-infected cells and protect mice against RSV infection without [...] Read more.
Background: Despite considerable efforts toward vaccine development in past decades, no effective vaccines against respiratory syncytial virus (RSV) are available. Recently, we showed that an optimized formalin concentration can preserve prefusion protein (pre-F) on RSV-infected cells and protect mice against RSV infection without causing enhanced respiratory disease (ERD). Here, we sought to further stabilize pre-F on RSV virions by optimizing the production of FI-RSV. Methods: Freshly produced RSV virions were treated with formalin under different concentrations to obtained an opti-FI-RSV vaccine with high pre-F level. Immunogenicity and safety of opti-FI-RSV were evaluated in Balb/c mice and cotton rats. Results: Using 0.0156–0.1778% formalin, we successfully preserved pre-F on virions. This opti-FI-RSV exhibited improved immunogenicity and efficacy without causing ERD. Surprisingly, opti-FI-RSV, with a pre-F-dominant immunogen, still caused ERD after immunization with a suboptimal dose or when the neutralizing antibody titers declined. ERD was avoided by coadministering opti-FI-RSV with CpG + MPLA adjuvant, which subsequently induced a Th1-biasing immune response and, more importantly, significantly improved antibody avidity. Conclusions: Our study provides a new method to obtain a novel FI-RSV vaccine with a high pre-F level and may provide a reference for developing other inactivated vaccines. Our findings also emphasize that appropriate adjuvants are critical for nonreplicating vaccines. Full article
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