title: Addition of the immunostimulatory oligonucleotide IMT504 to a seasonal flu vaccine increases hemagglutinin antibody titers in young adult and elder rats, and expands the anti-hemagglutinin antibody repertoire.
abstract: Flu vaccines are partially protective in infants and elder people. New adjuvants such as immunostimulatory oligonucleotides (ODNs) are strong candidates to solve this problem, because a combination with several antigens has demonstrated effectiveness. Here, we report that IMT504, the prototype of a major class of immunostimulatory ODNs, is a potent adjuvant of the influenza vaccine in young adult and elderly rats. Flu vaccines that use virosomes or whole viral particles as antigens were combined with IMT504 and injected in rats. Young adult and elderly animals vaccinated with IMT504-adjuvated preparations reached antibody titers 20-fold and 15-fold higher than controls, respectively. Antibody titers remained high throughout a 120 day-period. Animals injected with the IMT504-adjuvated vaccine showed expansion of the anti-hemagglutinin antibody repertoire and a significant increase in the antibody titer with hemagglutination inhibition capacity when confronted to viral strains included or not in the vaccine. This indicates that the addition of IMT504 in flu vaccines may contribute to the development of significant cross-protective immune response against shifted or drifted flu strains.
authors.affiliation: Centro de Ciencia y Tecnología "Dr. Cesar Milstein," National Research Council (CONICET) , Buenos Aires, Argentina. alemontaner@hotmail.com
authors.forename: Alejandro Daniel
authors.initials: AD
authors.lastname: Montaner
authors.forename: Analía
authors.initials: A
authors.lastname: Denichilo
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Rodríguez
authors.forename: Juan
authors.initials: J
authors.lastname: Fló
authors.forename: Ricardo Agustin
authors.initials: RA
authors.lastname: López
authors.forename: Andrea
authors.initials: A
authors.lastname: Pontoriero
authors.forename: Vilma
authors.initials: V
authors.lastname: Savy
authors.forename: Elsa
authors.initials: E
authors.lastname: Baumeister
authors.forename: Ronald
authors.initials: R
authors.lastname: Frank
authors.forename: Jorge
authors.initials: J
authors.lastname: Zorzopulos
authors.forename: Fernanda
authors.initials: F
authors.lastname: Elías
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006388:Hemagglutinins / Q000737:chemistry / Q000276:immunology; D007106:Immune Sera / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D006388:Hemagglutinins; C514285:IMT504; D007106:Immune Sera; D007252:Influenza Vaccines; D009838:Oligodeoxyribonucleotides; D014764:Viral Proteins; D009439:Neuraminidase