title: Live vaccines for human metapneumovirus designed by reverse genetics.
abstract: Human metapneumovirus (HMPV) was first described in 2001 and has quickly become recognized as an important cause of respiratory tract disease worldwide, especially in the pediatric population. A vaccine against HMPV is required to prevent severe disease associated with infection in infancy. The primary strategy is to develop a live-attenuated virus for intranasal immunization, which is particularly well suited against a respiratory virus. Reverse genetics provides a means of developing highly characterized 'designer' attenuated vaccine candidates. To date, several promising vaccine candidates have been developed, each using a different mode of attenuation. One candidate involves deletion of the G glycoprotein, providing attenuation that is probably based on reduced efficiency of attachment. A second candidate involves deletion of the M2-2 protein, which participates in regulating RNA synthesis and whose deletion has the advantageous property of upregulating transcription and increasing antigen synthesis. A third candidate involves replacing the P protein gene of HMPV with its counterpart from the related avian metapneumovirus, thereby introducing attenuation owing to its chimeric nature and host range restriction. Another live vaccine strategy involves using an attenuated parainfluenza virus as a vector to express HMPV protective antigens, providing a bivalent pediatric vaccine. Additional modifications to provide improved vaccines will also be discussed.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50, Room 6505, 50 South Dr. MSC 8007, Bethesda, MD 20892-8007, USA. ubuchholz@niaid.nih.gov
authors.forename: Ursula J
authors.initials: UJ
authors.lastname: Buchholz
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D002675:Child, Preschool; D003429:Cross Reactions; D015195:Drug Design; D017353:Gene Deletion; D014644:Genetic Variation; D005822:Genetic Vectors / Q000378:metabolism; D016679:Genome, Viral; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D029121:Metapneumovirus / Q000145:classification / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D018184:Paramyxoviridae Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D011995:Recombination, Genetic; D012703:Serotyping; D014611:Vaccination / Q000639:trends; D014613:Vaccines, Attenuated / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
chemical_list: D000956:Antigens, Viral; C484233:G glycoprotein, human metapneumovirus; D006023:Glycoproteins; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D014765:Viral Vaccines