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

► 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 antibo...

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Published inVaccine 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
LanguageEnglish
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
Online AccessGet full text
ISSN0264-410X
1873-2518
1873-2518
DOI10.1016/j.vaccine.2011.10.093

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Abstract ► 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.
AbstractList Highlights► 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.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.
► 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.
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.
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.
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.
Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN) super(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) super(+) CD11c super(+ DCs and both CD4) super(+) 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.
Highlights * 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.
Author Fukuiwa, Tatsuya
Fujihashi, Keiko
Asanuma, Hideki
Gilbert, Rebekah S.
Fujihashi, Kohtaro
Sata, Tetsutaro
Zamri, Normaiza Binti
Fukuyama, Yoshiko
Sekine, Shinichi
Tokuhara, Daisuke
Tashiro, Masato
AuthorAffiliation 1 Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, JAPAN
3 Department of Applied Biochemistry, School or Engineering, Tokai University, Hiratsuka-shi, Kanagawa, JAPAN
2 Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
4 Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, JAPAN
AuthorAffiliation_xml – name: 3 Department of Applied Biochemistry, School or Engineering, Tokai University, Hiratsuka-shi, Kanagawa, JAPAN
– name: 1 Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, JAPAN
– name: 4 Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, JAPAN
– name: 2 Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
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  givenname: Hideki
  surname: Asanuma
  fullname: Asanuma, Hideki
  organization: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan
– sequence: 2
  givenname: Normaiza Binti
  surname: Zamri
  fullname: Zamri, Normaiza Binti
  organization: Department of Applied Biochemistry, School or Engineering, Tokai University, Hiratsuka-shi, Kanagawa, Japan
– sequence: 3
  givenname: Shinichi
  surname: Sekine
  fullname: Sekine, Shinichi
  organization: Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
– sequence: 4
  givenname: Yoshiko
  surname: Fukuyama
  fullname: Fukuyama, Yoshiko
  organization: Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
– sequence: 5
  givenname: Daisuke
  surname: Tokuhara
  fullname: Tokuhara, Daisuke
  organization: Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
– sequence: 6
  givenname: Rebekah S.
  surname: Gilbert
  fullname: Gilbert, Rebekah S.
  organization: Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
– sequence: 7
  givenname: Tatsuya
  surname: Fukuiwa
  fullname: Fukuiwa, Tatsuya
  organization: Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
– sequence: 8
  givenname: Keiko
  surname: Fujihashi
  fullname: Fujihashi, Keiko
  organization: Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
– sequence: 9
  givenname: Tetsutaro
  surname: Sata
  fullname: Sata, Tetsutaro
  organization: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan
– sequence: 10
  givenname: Masato
  surname: Tashiro
  fullname: Tashiro, Masato
  organization: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan
– sequence: 11
  givenname: Kohtaro
  surname: Fujihashi
  fullname: Fujihashi, Kohtaro
  email: kohtarof@uab.edu
  organization: Department of Pediatric Dentistry, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/22100889$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2011 Elsevier Ltd
Elsevier Ltd
Copyright © 2011 Elsevier Ltd. All rights reserved.
Copyright Elsevier Limited Jan 17, 2012
2011 Elsevier Ltd. All rights reserved. 2011
Copyright_xml – notice: 2011 Elsevier Ltd
– notice: Elsevier Ltd
– notice: Copyright © 2011 Elsevier Ltd. All rights reserved.
– notice: Copyright Elsevier Limited Jan 17, 2012
– notice: 2011 Elsevier Ltd. All rights reserved. 2011
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DOI 10.1016/j.vaccine.2011.10.093
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Influenza
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SSID ssj0005319
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Snippet ► 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...
Highlights► 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...
Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)³ as a dendritic cell (DC)-targeting double mucosal adjuvant elicited...
Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)(3) as a dendritic cell (DC)-targeting double mucosal adjuvant elicited...
Highlights * 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...
Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN) super(3 as a dendritic cell (DC)-targeting double mucosal adjuvant...
Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN) 3 as a dendritic cell (DC)-targeting double mucosal adjuvant elicited...
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proquest
pubmed
crossref
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elsevier
SourceType Open Access Repository
Aggregation Database
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Enrichment Source
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StartPage 803
SubjectTerms 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
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Title A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging
URI https://www.clinicalkey.com/#!/content/1-s2.0-S0264410X11017439
https://www.clinicalkey.es/playcontent/1-s2.0-S0264410X11017439
https://dx.doi.org/10.1016/j.vaccine.2011.10.093
https://www.ncbi.nlm.nih.gov/pubmed/22100889
https://www.proquest.com/docview/1618948371
https://www.proquest.com/docview/1678529968
https://www.proquest.com/docview/915040086
https://www.proquest.com/docview/920802282
https://pubmed.ncbi.nlm.nih.gov/PMC3253905
Volume 30
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