Design and Computational Analysis of a Chimeric Avian Influenza Antigen: A Yeast-displayed, Universal and Cross-protective Vaccine Candidate

Abstract

AbstractBackgroundA cross-protective avian influenza vaccine candidate can be designed by using a preserved antigen against mutation in various subtypes of influenza. M2e peptide sequence has remained remarkably unchanged in influenza type A isolated since 1918.MethodsA consensus sequence of M2e peptide was obtained from 31 sequences of H5N8, H5N1, H9N2 and H7N9 subtypes of avian influenza virus isolated from 7 avian species in 5 Asian countries. A partial sequence of flagellin was considered as an adjuvant. Subsequently, two chimeric antigens were designed to be virtually cloned and expressed using PYD1 vector and EBY100 yeast strain. The stability and conformational features of these two antigens were assessed through molecular dynamic (MD) simulations. The detectability of vaccine candidates by a specific monoclonal antibody (MAb148) were estimated through docking studies.ResultsIn spite of significant compactness and stability of the first candidate in comparison with the second design, it was less detectable by MAb148. Contrary to the first chimeric antigen, Van der Waals, electrostatic and binding energies of the interaction of the second antigen with MAb148 were significantly closer to the positive control. It is shown that epitopes of the second chimeric antigen could be correctly located in the specific pocket of CDR region of MAb148.ConclusionThe second chimeric antigen could be considered as a yeast-displayed avian influenza vaccine candidate due to the capability of provoking humoral immunity and innate immune system by M2e and flagellin respectively.