Recombinant Measles AIK-C Vaccine Strain Expressing Influenza HA Protein

Abstract

Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton rats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split vaccine were used as positive controls, and higher HI antibodies were detected 3 weeks after the first dose. Following the challenge of A/California/07/2009(H1N1pdm), higher viral loads (107 TCID50/g) were detected in the lung homogenates of cotton rats immunized with the empty vector (MVAIK) or control groups than those immunized with MVAIK/Pdm HA (103 TCID50/g) or the group immunized with HA split vaccine (105 TCID50/g). Histopathologically, destruction of the alveolar structure, swelling of broncho-epithelial cells, and thickening of the alveolar wall with infiltration of inflammatory cells and HA antigens were detected in lung tissues obtained from non-immunized rats and those immunized with the empty vector after the challenge, but not in those immunized with the HA spilt or MVAIK/PdmHA vaccine. Lower levels of IFN-α, IL-1β, and TNF-α mRNA, and higher levels of IFN-γ mRNA were found in the lung homogenates of the MVAIK/PdmHA group. Higher levels of IFN-γ mRNA were detected in spleen cell culture from the MVAIK/PdmHA group stimulated with UV-inactivated A/California/07/2009(H1N1pdm). In conclusion, the recombinant MVAIK vaccine expressing influenza HA protein induced protective immune responses in cotton rats.