Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse genetics are attenuated and efficacious in African green monkeys

Vaccine. 2005 Sep 7;23(38):4631-46. doi: 10.1016/j.vaccine.2005.04.035.

Abstract

A set of recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1) vaccine candidates was evaluated for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs). Temperature sensitive (ts) and non-ts attenuating (att) mutations in the P/C and L genes were introduced individually or in various combinations into rHPIV1, including the C(R84G) and HN(T553A) mutations identified in the present work and the C(F170S), L(Y942A), and L(L992C) mutations identified previously. The rHPIV1 vaccine candidates exhibited a spectrum of attenuation in AGMs. One genetically and phenotypically stable vaccine candidate, rC(R84G/F170S)L(Y942A/L992C), was attenuated and efficacious in AGMs and is a promising live attenuated intranasal HPIV1 vaccine candidate suitable for clinical evaluation.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Disease Models, Animal
  • Humans
  • Macaca mulatta
  • Parainfluenza Vaccines / administration & dosage
  • Parainfluenza Vaccines / genetics
  • Parainfluenza Vaccines / immunology*
  • Parainfluenza Virus 1, Human / genetics
  • Parainfluenza Virus 1, Human / immunology*
  • Parainfluenza Virus 1, Human / pathogenicity
  • Point Mutation
  • Respirovirus Infections / prevention & control
  • Temperature
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology*
  • Viral Proteins / genetics
  • Viral Proteins / immunology

Substances

  • Antibodies, Viral
  • Parainfluenza Vaccines
  • Vaccines, Attenuated
  • Viral Proteins