Department of Microbiology and Physiological Systems
Immunoprophylaxis and Therapy | Microbiology
Respiratory syncytial virus (RSV) is a significant respiratory pathogen but no vaccine is available. RSV infections present 2 major, unique problems. First, humans can experience repeated infections caused by the same virus sero-group indicating that protective memory responses to RSV infection are defective. Second, most people have been infected with RSV by age 5. Immune responses to these infections, while poorly protective, could impact the effectiveness of a vaccine. The goal of this study was to assess the generation of protective immune responses in mice previously infected with RSV by virus-like particle (VLP) vaccine candidates containing a stabilized pre-fusion form of the RSV F protein or a stabilized post-fusion F protein. We report that a single immunization of RSV-experienced animals with a stabilized pre-fusion F protein VLP stimulated high titers of neutralizing antibody while a single injection of a post-fusion F protein VLP or a second RSV infection only weakly stimulated neutralizing antibody titers. These results suggest that prior RSV infection can induce neutralizing antibody memory responses, which can be activated by pre-F protein VLPs but not by post-F protein VLPs or a subsequent infection. Thus the F protein conformation has a major impact on enhancing production of neutralizing antibodies in RSV-experienced animals. Furthermore, although both VLPs contained the same RSV G protein, the pre-F VLP stimulated significantly higher titers of total anti-G protein IgG than the post-F VLP in both naive and RSV-experienced animals. Thus the F protein conformation also influences anti-G protein responses.
F protein antibodies, G protein antibodies, respiratory syncytial virus, vaccine, virus-like particles
Rights and Permissions
© 2017 Lori M. Cullen, Madelyn R. Schmidt, and Trudy G. Morrison. Published with license by Taylor and Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
DOI of Published Version
Hum Vaccin Immunother. 2017 Dec 2;13(12):2814-2823. doi: 10.1080/21645515.2017.1329069. Epub 2017 Jun 12. Link to article on publisher's site
Human vaccines and immunotherapeutics
Cullen, Lori M.; Schmidt, Madelyn R.; and Morrison, Trudy G., "The importance of RSV F protein conformation in VLPs in stimulation of neutralizing antibody titers in mice previously infected with RSV" (2017). Open Access Articles. 3335.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.