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Sci Transl Med. 2015 Nov 4;7(312):312ra175. doi: 10.1126/scitranslmed.aac8463.

A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children.

Author information

1
Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. rkarron@jhu.edu.
2
RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy, Immunology, and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
3
Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
4
Seattle Children's Research Institute, University of Washington, Seattle, WA 98101, USA.

Abstract

Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and a safe and effective vaccine for use in infancy and early childhood is needed. We previously showed that deletion of the coding sequence for the viral M2-2 protein (ΔM2-2) down-regulated viral RNA replication and up-regulated gene transcription and antigen synthesis, raising the possibility of development of an attenuated vaccine with enhanced immunogenicity. RSV MEDI ΔM2-2 was therefore evaluated as a live intranasal vaccine in adults, RSV-seropositive children, and RSV-seronegative children. When results in RSV-seronegative children were compared to those achieved with the previous leading live attenuated RSV candidate vaccine, vaccine virus shedding was significantly more restricted, yet the postvaccination RSV-neutralizing serum antibody achieved [geometric mean titer (GMT) = 1:97] was significantly greater. Surveillance during the subsequent RSV season showed that several seronegative RSV MEDI ΔM2-2 recipients had substantial antibody rises without reported illness, suggesting that the vaccine was protective yet primed for anamnestic responses to RSV. Rational design appears to have yielded a candidate RSV vaccine that is intrinsically superior at eliciting protective antibody in RSV-naïve children and highlights an approach for the development of live attenuated RSV vaccines.

Comment in

PMID:
26537255
PMCID:
PMC6342448
DOI:
10.1126/scitranslmed.aac8463
[Indexed for MEDLINE]
Free PMC Article

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