Induction of protection against divergent H5N1 influenza viruses using a recombinant fusion protein linking influenza M2e to Onchocerca volvulus activation associated protein-1 (ASP-1) adjuvant.
Our previous studies have shown the adjuvanticity of an Onchocerca volvulus recombinant protein, Ov-ASP-1 (ASP-1), when administered in an aqueous formulation with bystander vaccine antigens or commercial vaccines. In this study, we reported a novel formulation that took advantage of the protein nature of the ASP-1 adjuvant by creating recombinant fusion protein vaccines linking the highly conserved extracellular domain of M2 protein (M2e) consensus sequence of H5N1 influenza viruses with the ASP-1 adjuvant. Two recombinant fusion proteins designated M2e-ASP-1 and M2e3-ASP-1 were studied, in which ASP-1 was fused with one or three tandem copies of the M2e antigen. Our results show that these novel recombinant influenza vaccines, particularly M2e3-ASP-1, induced strong anti-M2e-specific humoral and cellular immune responses in the established mouse model. Furthermore, M2e3-ASP-1 was able to provide significant cross-clade protection against divergent H5N1 viruses. Consequently, this study has demonstrated a potential novel vaccine formulation that could provide a complementary prophylactic strategy in preventing the threat of future influenza outbreak resulting from rapid evolution of the H5N1 virus and co-circulation of multiple antigenic variants in various regions.
Zhao
Guangyu
G
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Du
Lanying
L
Xiao
Wenjun
W
Sun
Shihui
S
Lin
Yongping
Y
Chen
Min
M
Kou
Zhihua
Z
He
Yuxian
Y
Lustigman
Sara
S
Jiang
Shibo
S
Zheng
Bo-Jian
BJ
Zhou
Yusen
Y
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology*; D056738:Cross Protection; D005260:Female; D015801:Helminth Proteins / Q000008:administration & dosage / Q000276:immunology*; D007111:Immunity, Cellular; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D017181:Onchocerca volvulus; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000276:immunology*; D000086082:Viroporin Proteins
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000947:Antigens, Helminth; D015801:Helminth Proteins; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D018074:Vaccines, Conjugate; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C414408:Ov-ASP-1 protein, Onchocerca volvulus