Generation of a Vaccine against Group B Streptococcal Infection on the Basis of a Cold-Adapted Influenza A Virus

Abstract

The aim of this study was to develop a cold-adapted influenza A (H7N9) strain-based vector vaccine expressing epitopes of conserved lipoprotein of Streptococcus agalactiae. Recombinant hemagglutinin (HA) genes of live attenuated influenza vaccine (LAIV) strain A/Anhui/1/2013(H7N9) with insertions of group B Streptococcus (GBS) surface antigen ScaAB gene parts of different length in-frame between signal peptide and HA1 were constructed by means of reverse genetics. Viral vector vaccine H7-ScaAB-85 expressing the shortest (85 amino acids) polypeptide from lipoprotein ScaAB linked to HA via a flexible linker was genetically stable, replicated in embryonated chicken eggs and MDCK cells at the same level as cold-adapted influenza A (H7N9) strain. An increase of ScaAB polypeptide insertion length up to 141 amino acids resulted in a decrease of the viral replication level in both susceptible systems and intense mutagenesis of hybrid HA-gene of recombinant influenza A virus in the gene region encoding foreign bacterial lipoprotein. These findings suggest that H7-ScaAB-85 is a promising vaccine candidate, which should be further assessed using a mouse model.