A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging

• Published in: Vaccine Vol. 30; no. 4; pp. 803 - 812
• Main Authors: Asanuma, Hideki, Zamri, Normaiza Binti, Sekine, Shinichi, Fukuyama, Yoshiko, Tokuhara, Daisuke, Gilbert, Rebekah S., Fukuiwa, Tatsuya, Fujihashi, Keiko, Sata, Tetsutaro, Tashiro, Masato, Fujihashi, Kohtaro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 17.01.2012; Elsevier Limited
• Subjects: Adenoviruses; Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; adults; Age; Aged mice; Aging; Allergy and Immunology; Animals; Antibodies, Viral - immunology; Cytokines; Dendritic Cells - immunology; Drug dosages; Experiments; Female; Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage; Hemagglutinin Glycoproteins, Influenza Virus - immunology; hemagglutinins; Immunity, Mucosal; immunoglobulin A; Immunoglobulin A - immunology; Infectious diseases; Influenza; Influenza A virus - immunology; Influenza A virus - pathogenicity; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Ligands; lymph nodes; Medical research; Membrane Proteins - administration & dosage; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mortality; mucosal immunity; Mucosal vaccine; nasal cavity; Oligodeoxyribonucleotides - administration & dosage; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Plasma; plasmids; Respiratory tract; Streptococcus infections; Th1 Cells - immunology; Th2 Cells - immunology; Vaccines; viruses; Aged mice; Mucosal vaccine; Influenza; DC
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2011.10.093

► We examined whether pFL and CpG-ODN could induce influenza-specific protective immunity in aged mice. ► A combination of pFL and CpG-ODN elicits a balanced Th1 and Th2 response. ► Nasal pFL and CpG-ODN induce protective influenza-specific mucosal immunity in aged mice. ► PR8 HA-specific IgA antibodies are essential for the prevention of influenza infection in the upper respiratory tract. Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN) 3 as a dendritic cell (DC)-targeting double mucosal adjuvant elicited ovalbumin-specific secretory IgA (S-IgA) antibody (Ab) responses, we examined whether this double adjuvant could induce influenza-specific protective immunity in aged mice. A double adjuvant plus A/Puerto Rico/8/34 (PR8) hemagglutinin (HA) induced increased numbers of CD11b + CD11c + DCs and both CD4 + Th1- and Th2-type responses in the nasopharyngeal-associated lymphoreticular tissue, nasal passages and cervical lymph nodes. Further, increased levels of PR8 HA-specific S-IgA Ab responses were detected in the upper respiratory tact (URT) of aged and young adult mice given nasal PR8 HA with this double adjuvant. Thus, when mice were challenged with PR8 virus via the nasal route, both aged and young adult mice given nasal vaccine exhibited complete protection. Further, IgA-deficient mice nasally immunized with a double adjuvant influenza vaccine failed to provide protection against PR8 challenge. These results indicate that a nasal double adjuvant successfully induces PR8 HA-specific IgA Ab responses in both young adult and aged mice, which are essential for the prevention of influenza infection in the murine URT.