Journal article
Vaccination with a Single-Cycle Respiratory Syncytial Virus Is Immunogenic and Protective in Mice
The Journal of immunology (1950), Vol.202(11), pp.3234-3245
06/01/2019
DOI: 10.4049/jimmunol.1900050
PMCID: PMC6529240
PMID: 31004010
Abstract
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.
Details
- Title: Subtitle
- Vaccination with a Single-Cycle Respiratory Syncytial Virus Is Immunogenic and Protective in Mice
- Creators
- Megan E. Schmidt - University of IowaAntonius G. P. Oomens - Oklahoma State UniversitySteven M. Varga - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.202(11), pp.3234-3245
- DOI
- 10.4049/jimmunol.1900050
- PMID
- 31004010
- PMCID
- PMC6529240
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Amer Assoc Immunologists
- Number of pages
- 12
- Grant note
- P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) University of Iowa Carver College of Medicine P20GM103648 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R01AI124093; T32AI007485; P20GM103648 / National Institute of General Medical Sciences of the National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) HR08-1395 / Oklahoma Center for the Advancement of Science and Technology T32AI007485 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) P30CA086862 / National Cancer Institute of the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Holden Comprehensive Cancer Center Department of Microbiology and Immunology at the University of Iowa
- Language
- English
- Date published
- 06/01/2019
- Academic Unit
- Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Community and Behavioral Health
- Record Identifier
- 9984297325902771
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