Live vaccines for human metapneumovirus designed by reverse genetics

Expert Rev Vaccines. 2006 Oct;5(5):695-706. doi: 10.1586/14760584.5.5.695.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antigens, Viral / genetics*
  • Antigens, Viral / immunology
  • Child, Preschool
  • Cross Reactions
  • Drug Design*
  • Gene Deletion
  • Genetic Variation
  • Genetic Vectors / metabolism
  • Genome, Viral*
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Humans
  • Immunization Schedule
  • Infant
  • Infant, Newborn
  • Metapneumovirus / classification
  • Metapneumovirus / genetics*
  • Metapneumovirus / immunology
  • Mutation
  • Paramyxoviridae Infections / epidemiology
  • Paramyxoviridae Infections / immunology
  • Paramyxoviridae Infections / prevention & control*
  • Recombination, Genetic
  • Serotyping
  • Vaccination / trends
  • Vaccines, Attenuated / genetics
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Vaccines / biosynthesis
  • Viral Vaccines / genetics*
  • Viral Vaccines / immunology

Substances

  • Antigens, Viral
  • G glycoprotein, human metapneumovirus
  • Glycoproteins
  • Vaccines, Attenuated
  • Viral Proteins
  • Viral Vaccines