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Journal of Virology, February 2006, p. 2034-2044, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.2034-2044.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cytotoxic T-Lymphocyte Epitope Vaccination Protects against Human Metapneumovirus Infection and Disease in Mice{dagger}

Karen A. Herd,1 Suresh Mahalingam,2 Ian M. Mackay,1 Michael Nissen,1,3 Theo P. Sloots,1 and Robert W. Tindle1*

Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, and Clinical Medical Virology Centre, University of Queensland,1 School of Health Sciences, University of Canberra,2 Department of Infectious Diseases, Royal Children's Hospital, Brisbane, Australia3

Received 3 August 2005/ Accepted 2 December 2005

Human metapneumovirus (hMPV) has emerged as an important human respiratory pathogen causing upper and lower respiratory tract infections in young children and older adults. In addition, hMPV infection is associated with asthma exacerbation in young children. Recent epidemiological evidence indicates that hMPV may cocirculate with human respiratory syncytial virus (hRSV) and mediate clinical disease similar to that seen with hRSV. Therefore, a vaccine for hMPV is highly desirable. In the present study, we used predictive bioinformatics, peptide immunization, and functional T-cell assays to define hMPV cytotoxic T-lymphocyte (CTL) epitopes recognized by mouse T cells restricted through several major histocompatibility complex class I alleles, including HLA-A*0201. We demonstrate that peptide immunization with hMPV CTL epitopes reduces viral load and immunopathology in the lungs of hMPV-challenged mice and enhances the expression of Th1-type cytokines (gamma interferon and interleukin-12 [IL-12]) in lungs and regional lymph nodes. In addition, we show that levels of Th2-type cytokines (IL-10 and IL-4) are significantly lower in hMPV CTL epitope-vaccinated mice challenged with hMPV. These results demonstrate for the first time the efficacy of an hMPV CTL epitope vaccine in the control of hMPV infection in a murine model.

* Corresponding author. Mailing address: Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Herston Road, Herston QLD 4029, Australia. Phone: 61-7-3636-8716. Fax: 61-7-3636-1401. E-mail: r.tindle{at}uq.edu.au.

{dagger} Contribution no. 221 of the Sir Albert Sakzewski Virus Research Centre.

Journal of Virology, February 2006, p. 2034-2044, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.2034-2044.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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