Vaccination with a Single-Cycle Respiratory Syncytial Virus Is Immunogenic and Protective in Mice.

Authors:
Megan E Schmidt
Megan E Schmidt
University of Iowa
Iowa City | United States
Steven M Varga
Steven M Varga
University of Iowa

J Immunol 2019 Jun 19;202(11):3234-3245. Epub 2019 Apr 19.

Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242;

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory tract infection in infants and young children, but no vaccine is currently available. Live-attenuated vaccines represent an attractive immunization approach; however, balancing attenuation while retaining sufficient immunogenicity and efficacy has prevented the successful development of such a vaccine. Recently, a recombinant RSV strain lacking the gene that encodes the matrix (M) protein (RSV M-null) was developed. The M protein is required for virion assembly following infection of a host cell but is not necessary for either genome replication or gene expression. Therefore, infection with RSV M-null produces all viral proteins except M but does not generate infectious virus progeny, resulting in a single-cycle infection. We evaluated RSV M-null as a potential vaccine candidate by determining its pathogenicity, immunogenicity, and protective capacity in BALB/c mice compared with its recombinant wild-type control virus (RSV recWT). RSV M-null-infected mice exhibited significantly reduced lung viral titers, weight loss, and pulmonary dysfunction compared with mice infected with RSV recWT. Despite its attenuation, RSV M-null infection induced robust immune responses of similar magnitude to that elicited by RSV recWT. Additionally, RSV M-null infection generated serum Ab and memory T cell responses that were similar to those induced by RSV recWT. Importantly, RSV M-null immunization provided protection against secondary viral challenge by reducing lung viral titers as efficiently as immunization with RSV recWT. Overall, our results indicate that RSV M-null combines attenuation with high immunogenicity and efficacy and represents a promising novel live-attenuated RSV vaccine candidate.

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Source
http://dx.doi.org/10.4049/jimmunol.1900050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529240PMC
June 2019
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References

(Supplied by CrossRef)
Live-attenuated respiratory syncytial virus vaccines.
Karron et al.
Curr. Top. Microbiol. Immunol. 2013

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