Early protection against influenza by pandemic live attenuated influenza vaccines

Abstract

Live attenuated cold-adapted (ca) influenza vaccine (LAIV) is an effective tool for the control of influenza, most likely due to their ability to induce both humoral and cellular immune responses, easy application and relatively low manufacturing costs. Attenuated cold-adapted vaccine strains that have achieved a satisfactory balance between restricted replication and high immunogenicity are desirable. The immunogenicity of live attenuated vaccines may depend upon the interplay between its ability to induce pro-inflammatory cytokine responses and the relative sensitivity of the attenuated vaccine strain to an antiviral effect of these cytokines. To better understand the relationship between attenuation and induction of innate immunity as well as contribution of the early cytokine response to the relative immunogenicity of LAIVs, we have studied early protection induced by LAIV in vivo as well as early cytokine response in human cells macrophage origin in response to infection with vaccine strains or epidemic virus.
 The aim of this study was to investigate the early immune response and protective activity in female CBA mice intranasally immunized with cold-adapted influenza vaccine strains of different genome compositions of 5:3 or 6:2. For experimental infection pandemic influenza viruses A/South Africa/3626/13 (H1N1)pdm09 and A/New York/61/15 (H1N1)pdm09 were used to be administered to animals at a dose of 106 EID50 at day 3 after immunization (challenge infection). Although challenge viruses replicate at mice lungs at various, extend, on day 10 after immunization mice were protected from death from 60 up to 80%. Reassortants LAIV did not differ statistically on these levels.
 Study of the expression of IFN- and IFN- genes in human lung macrophage line cells THP-1 in vitro have shown that macrophages stimulated with vaccine strains with the genome formula 6:2 and 5:3, had a sufficient level of expression of these genes, comparable to that, as in infection with wild virus type A/South Africa/3626/13 (H1N1)pdm09. These data may indicate that surface proteins of influenza A virus are involved in the process of stimulation of the IFN- and IFN- genes.