UMMS Affiliation

Department of Microbiology and Physiological Systems; Program in Immunology and Microbiology

Publication Date

11-5-2015

Document Type

Article

Disciplines

Immunity | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Medical Immunology | Respiratory Tract Diseases | Translational Medical Research | Virology

Abstract

BACKGROUND: Virus-like particles (VLPs) based on Newcastle disease virus (NDV) core proteins, M and NP, and containing two chimera proteins, F/F and H/G, composed of the respiratory syncytial virus (RSV) fusion protein (F) and glycoprotein (G) ectodomains fused to the transmembrane and cytoplasmic domains of the NDV F and HN proteins, respectively, stimulate durable, protective anti-RSV neutralizing antibodies in mice. Furthermore, immunization of mice with a VLP containing a F/F chimera protein with modifications previously reported to stabilize the pre-fusion form of the RSV F protein resulted in significantly improved neutralizing antibody titers over VLPs containing the wild type F protein. The goal of this study was to determine if VLPs containing the pre-fusion form of the RSV F protein stimulated protective immune responses in cotton rats, a more RSV permissive animal model than mice.

METHODS: Cotton rats were immunized intramuscularly with VLPs containing stabilized pre-fusion F/F chimera protein as well as the H/G chimera protein. The anti-RSV F and RSV G antibody responses were determined by ELISA. Neutralizing antibody titers in sera of immunized animals were determined in plaque reduction assays. Protection of the animals from RSV challenge was assessed. The safety of the VLP vaccine was determined by monitoring lung pathology upon RSV challenge of immunized animals.

RESULTS: The Pre-F/F VLP induced neutralizing titers that were well above minimum levels previously proposed to be required for a successful vaccine and titers significantly higher than those stimulated by RSV infection. In addition, Pre-F/F VLP immunization stimulated higher IgG titers to the soluble pre-fusion F protein than RSV infection. Cotton rats immunized with Pre-F/F VLPs were protected from RSV challenge, and, importantly, the VLP immunization did not result in enhanced respiratory disease upon RSV challenge.

CONCLUSIONS: VLPs containing the pre-fusion RSV F protein have characteristics required for a safe, effective RSV vaccine.

Rights and Permissions

Citation: J Transl Med. 2015 Nov 5;13:350. doi: 10.1186/s12967-015-0705-8. Link to article on publisher's site

DOI of Published Version

10.1186/s12967-015-0705-8

Comments

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Related Resources

Link to Article in PubMed

Keywords

Respiratory syncytial virus, Vaccine, Fusion protein, Neutralizing antibody titers, Cotton rats

Journal/Book/Conference Title

Journal of translational medicine

PubMed ID

26541285

Creative Commons License

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

 
 

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