Immunogenicity and efficacy of the monovalent, trivalent and quadrivalent intranasal live attenuated influenza vaccines containing different pdmH1N1 strains

Vaccine. 2018 Nov 12;36(46):6944-6952. doi: 10.1016/j.vaccine.2018.10.002. Epub 2018 Oct 12.

Abstract

A ferret challenge study was conducted to address the efficacy of the egg-based and Madin-Darby canine kidney (MDCK)-based live attenuated influenza vaccine (LAIV) strains. Vaccines derived as 6:2 reassortants from the A/Leningrad/134/17/57 master donor strain and the HA and NA components from the A/California/07/2009 (A/Cal)- and A/Michigan/45/2015 (A/Mich)-like strains of type A H1N1 influenza virus were used in the study. Monovalent, trivalent and quadrivalent formulations of the LAIV containing either of the two H1N1 strains were analysed. A total of ten groups of six animals each were immunised intranasally (i.n.) with a single dose of 0.5-ml vaccine formulation or placebo and challenged on day 28 with the homologous wild-type A/Cal or A/Mich strain. Immune response post immunisation and virus replication post challenge were studied. Both the strains derived from embryonated eggs or MDCK cells, irrespective of the vaccine valency, were capable of rendering complete protection from virus replication in the lung. The A/Mich vaccine strain showed higher immune titres and efficacy than the A/Cal vaccine strain in all the vaccine formulations. The haemagglutination inhibition and virus neutralisation antibody titres were induced, and the reduction in the virus load in the respiratory tract was observed to be higher in animals treated with the monovalent formulation compared to the trivalent and quadrivalent formulations. Overall, it appears that the monovalent formulations render better protection from infection and would therefore be the best candidate during a pandemic.

Keywords: Efficacy; Ferret; Immunogenicity; Pandemic H1N1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Disease Models, Animal
  • Female
  • Ferrets
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunogenicity, Vaccine*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Neutralization Tests
  • Placebos / administration & dosage
  • Reassortant Viruses / immunology
  • Respiratory System / pathology
  • Respiratory System / virology
  • Treatment Outcome
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Influenza Vaccines
  • Placebos
  • Vaccines, Attenuated