Adjuvants and immunization strategies to induce influenza virus hemagglutinin stalk antibodies.
The global population remains vulnerable in the face of the next pandemic influenza virus outbreak, and reformulated vaccinations are administered annually to manage seasonal epidemics. Therefore, development of a new generation of vaccines is needed to generate broad and persistent immunity to influenza viruses. Here, we describe three adjuvants that enhance the induction of stalk-directed antibodies against heterologous and heterosubtypic influenza viruses when administered with chimeric HA proteins. Addavax, an MF59-like nanoemulsion, poly(I:C), and an RNA hairpin derived from Sendai virus (SeV) Cantell were efficacious intramuscularly. The SeV RNA and poly(I:C) also proved to be effective respiratory mucosal adjuvants. Although the quantity and quality of antibodies induced by the adjuvants varied, immunized mice demonstrated comparable levels of protection against challenge with influenza A viruses on the basis of HA stalk reactivity. Finally, we present that intranasally, but not intramuscularly, administered chimeric HA proteins induce mucosal IgA antibodies directed at the HA stalk.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Peter H
PH
Goff
Dirk
D
Eggink
Christopher W
CW
Seibert
Rong
R
Hai
Luis
L
Martínez-Gil
Florian
F
Krammer
Peter
P
Palese
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D004285:Dogs; D004655:Emulsions / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods*; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009690:Nucleic Acid Conformation; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology; D011136:Polysorbates / Q000008:administration & dosage; D012367:RNA, Viral / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D029082:Sendai virus / Q000235:genetics / Q000276:immunology; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology
C000590912:Addavax; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004655:Emulsions; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D013185:Squalene; D011070:Poly I-C