Strategies for intranasal delivery of vaccines

The vast majority of human pathogens colonize and invade at the mucosal surfaces. Preventing infection at these sites via mucosally active vaccines is a promising and rational approach for vaccine development. However, it is only recently that the stimulation of local immunity at the mucosal surfaces has become a primary objective in addition to inducing systemic immunity. This review describes vaccine formulations designed for mucosal delivery to the nasal-associated lymphoid tissue, via intranasal administration. The association of antigens with mucosal adjuvants and delivery systems is emphasised.

[1]  O. Ohtani,et al.  Lectin binding patterns in rat nasal-associated lymphoid tissue (NALT) and the influence of various types of lectin on particle uptake in NALT. , 2000, Archives of histology and cytology.

[2]  P. Ellner,et al.  Smallpox: Gone but not forgotten , 1998, Infection.

[3]  S. Endres,et al.  ISCOMATRIX Adjuvant Induces Efficient Cross-Presentation of Tumor Antigen by Dendritic Cells via Rapid Cytosolic Antigen Delivery and Processing via Tripeptidyl Peptidase II1 , 2009, The Journal of Immunology.

[4]  T. Himi,et al.  Epithelial barrier and antigen uptake in lymphoepithelium of human adenoids , 2011, Acta oto-laryngologica.

[5]  C. Chakraborti,et al.  Qualitative analysis of controlled release ciprofloxacin/carbopol 934 mucoadhesive suspension , 2011, Journal of advanced pharmaceutical technology & research.

[6]  R. Tyagi,et al.  Mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymers. , 2010, Recent patents on drug delivery & formulation.

[7]  I. Toth,et al.  Expression of maturation markers on murine dendritic cells in response to group A streptococcal lipopeptide vaccines. , 2009, Vaccine.

[8]  Jisheng Yang,et al.  Calorimetric studies of the interaction between sodium alginate and sodium dodecyl sulfate in dilute solutions at different pH values. , 2008, Carbohydrate research.

[9]  Y. Fujimura Evidence of M cells as portals of entry for antigens in the nasopharyngeal lymphoid tissue of humans , 2000, Virchows Archiv.

[10]  I. Toth,et al.  Simple synthetic toll-like receptor 2 ligands. , 2011, Bioorganic & medicinal chemistry letters.

[11]  S. Rossi,et al.  Characterization of rheological and mucoadhesive properties of three grades of chitosan hydrochloride. , 1997, Farmaco.

[12]  B. Lambrecht,et al.  Intranasal DNA vaccination induces potent mucosal and systemic immune responses and cross-protective immunity against influenza viruses. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[13]  S. Cryz,et al.  Safety and immunogenicity of intranasally administered inactivated trivalent virosome-formulated influenza vaccine containing Escherichia coli heat-labile toxin as a mucosal adjuvant. , 2000, The Journal of infectious diseases.

[14]  O’Hagan,et al.  The preparation and characterization of polymeric antigen delivery systems for oral administration. , 1998, Advanced drug delivery reviews.

[15]  Robert Ball,et al.  Adverse events reported following live, cold-adapted, intranasal influenza vaccine. , 2005, JAMA.

[16]  S Somavarapu,et al.  Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery. , 2005, Advanced drug delivery reviews.

[17]  K. Chandran,et al.  The viral sigma1 protein and glycoconjugates containing alpha2-3-linked sialic acid are involved in type 1 reovirus adherence to M cell apical surfaces. , 2003, Journal of virology.

[18]  S. Uhlig,et al.  Effects of the TLR2 Agonists MALP-2 and Pam3Cys in Isolated Mouse Lungs , 2010, PloS one.

[19]  F. Johansen,et al.  Regulation of the polymeric immunoglobulin receptor and IgA transport: New advances in environmental factors that stimulate pIgR expression and its role in mucosal immunity , 2011, Mucosal Immunology.

[20]  S. Zevgiti,et al.  A palmitoyl-tailed sequential oligopeptide carrier for engineering immunogenic conjugates. , 2007, Vaccine.

[21]  K. Chandran,et al.  The Viral σ1 Protein and Glycoconjugates Containing α2-3-Linked Sialic Acid Are Involved in Type 1 Reovirus Adherence to M Cell Apical Surfaces , 2003, Journal of Virology.

[22]  M. Herbst-Kralovetz,et al.  Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine. , 2011, Vaccine.

[23]  Melinda Fitzgerald,et al.  Immunol. Cell Biol. , 1995 .

[24]  L. Brown,et al.  Highly Immunogenic and Totally Synthetic Lipopeptides as Self-Adjuvanting Immunocontraceptive Vaccines1 , 2002, The Journal of Immunology.

[25]  R. Glück,et al.  Phase 1 Evaluation of Intranasal Virosomal Influenza Vaccine with and without Escherichia coli Heat-Labile Toxin in Adult Volunteers , 1999, Journal of Virology.

[26]  E. Meeusen,et al.  Alternative routes of mucosal immunization in large animals , 2004, Immunology and cell biology.

[27]  M. Cesta Normal Structure, Function, and Histology of Mucosa-Associated Lymphoid Tissue , 2006, Toxicologic pathology.

[28]  K. Mittenbühler,et al.  Lipopeptide adjuvants: monitoring and comparison of P3CSK4- and LPS-induced gene transcription. , 2002, International immunopharmacology.

[29]  L. BenMohamed,et al.  Lipopeptide epitopes extended by an Nϵ‐palmitoyl‐lysine moiety increase uptake and maturation of dendritic cells through a Toll‐like receptor‐2 pathway and trigger a Th1‐dependent protective immunity , 2004, European journal of immunology.

[30]  R. Obregon,et al.  Achieving polio eradication: a review of health communication evidence and lessons learned in India and Pakistan. , 2009, Bulletin of the World Health Organization.

[31]  S. Davis Nasal vaccines. , 2001, Advanced drug delivery reviews.

[32]  R. Walker,et al.  New strategies for using mucosal vaccination to achieve more effective immunization. , 1994, Vaccine.

[33]  W. Bessler,et al.  Bacterial lipopeptides constitute efficient novel immunogens and adjuvants in parenteral and oral immunization. , 1997, Behring Institute Mitteilungen.

[34]  D. W. Kim,et al.  Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses , 2010, BMC Immunology.

[35]  K. Haruma,et al.  Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid tissue , 2006, Medical Molecular Morphology.

[36]  B. Lambrecht,et al.  The positive adjuvant effect of chitosan on antigen-specific cell-mediated immunity after chickens vaccination with live Newcastle disease vaccine. , 2010, Veterinary immunology and immunopathology.

[37]  G. Wang,et al.  Intranasal Delivery of Cationic PLGA Nano/Microparticles- Loaded FMDV DNA Vaccine Encoding IL-6 Elicited Protective Immunity against FMDV Challenge , 2011, PloS one.

[38]  Ivo Que,et al.  Nasal vaccination with N-trimethyl chitosan and PLGA based nanoparticles: nanoparticle characteristics determine quality and strength of the antibody response in mice against the encapsulated antigen. , 2010, Vaccine.

[39]  A. Zuercher,et al.  Nasal-Associated Lymphoid Tissue Is a Mucosal Inductive Site for Virus-Specific Humoral and Cellular Immune Responses1 , 2002, The Journal of Immunology.

[40]  V. Dixit,et al.  Evaluation of ISCOM vaccines for mucosal immunization against hepatitis B , 2010, Journal of drug targeting.

[41]  J. Lowe,et al.  Chitosan as a nasal delivery system: the effect of chitosan solutions on in vitro and in vivo mucociliary transport rates in human turbinates and volunteers. , 1997, Journal of pharmaceutical sciences.

[42]  H. Kiyono,et al.  Nasal immune system: distinctive Th0 and Th1/Th2 type environments in murine nasal‐associated lymphoid tissues and nasal passage, respectively , 1998, European journal of immunology.

[43]  L. Sáenz,et al.  Chitosan formulations improve the immunogenicity of a GnRH-I peptide-based vaccine. , 2009, International journal of pharmaceutics.

[44]  H. Benson,et al.  Pharmaceutical aspects of intranasal delivery of vaccines using particulate systems. , 2009, Journal of pharmaceutical sciences.

[45]  T. Bowersock,et al.  Induction of systemic and mucosal immune response in cattle by intranasal administration of pig serum albumin in alginate microparticles. , 2001, Veterinary immunology and immunopathology.

[46]  B. Frisch,et al.  Liposomes as delivery systems for nasal vaccination: strategies and outcomes , 2010, Expert opinion on drug delivery.

[47]  P. Brandtzaeg Immune functions of nasopharyngeal lymphoid tissue. , 2011, Advances in oto-rhino-laryngology.

[48]  E. Jeung,et al.  Trans-10, cis-12-conjugated linoleic acid attenuates tumor necrosis factor-α production by lipopolysaccharide-stimulated porcine peripheral blood mononuclear cells through induction of interleukin-10. , 2011, Cytokine.

[49]  M. Amacker,et al.  A new and versatile virosomal antigen delivery system to induce cellular and humoral immune responses. , 2007, Vaccine.

[50]  K. Knutson,et al.  Flt3 ligand as a vaccine adjuvant in association with HER-2/neu peptide-based vaccines in patients with HER-2/neu-overexpressing cancers. , 2002, Blood.

[51]  Yinglei Xu,et al.  Chitosan Nanoparticles Act as an Adjuvant to Promote both Th1 and Th2 Immune Responses Induced by Ovalbumin in Mice , 2011, Marine drugs.

[52]  J. Remon,et al.  Spray-dried powders of starch and crosslinked poly(acrylic acid) as carriers for nasal delivery of inactivated influenza vaccine. , 2009, Vaccine.

[53]  L. Illum Nasal drug delivery--possibilities, problems and solutions. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[54]  R. Bodmeier,et al.  In situ gelling, bioadhesive nasal inserts for extended drug delivery: in vitro characterization of a new nasal dosage form. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[55]  R. Mrsny,et al.  In Vitro Evaluation of Microparticles and Polymer Gels for Use as Nasal Platforms for Protein Delivery , 1999, Pharmaceutical Research.

[56]  J. Mcghee,et al.  Novel vaccine development strategies for inducing mucosal immunity , 2012, Expert review of vaccines.

[57]  D. Jackson,et al.  Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys , 2010, Amino Acids.

[58]  W. Ricciardi The old Edward Jenner and the new public health: the future of vaccines in Europe. , 2008, European journal of public health.

[59]  D. Jackson,et al.  Intranasal vaccination with a lipopeptide containing a conformationally constrained conserved minimal peptide, a universal T cell epitope, and a self-adjuvanting lipid protects mice from group A streptococcus challenge and reduces throat colonization. , 2006, The Journal of infectious diseases.

[60]  W. Hennink,et al.  A step-by-step approach to study the influence of N-acetylation on the adjuvanticity of N,N,N-trimethyl chitosan (TMC) in an intranasal nanoparticulate influenza virus vaccine. , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[61]  A. Almeida,et al.  Solid lipid nanoparticles as a drug delivery system for peptides and proteins. , 2007, Advanced drug delivery reviews.

[62]  K. Kaur,et al.  Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein. , 2012, Molecular pharmaceutics.

[63]  S. Xiong,et al.  Intranasal delivery of chitosan-DNA vaccine generates mucosal SIgA and anti-CVB3 protection. , 2004, Vaccine.

[64]  A. Bozkır,et al.  Nasal Delivery of Vaccines , 2009 .

[65]  H. Alpár,et al.  Adjuvant synergy: The effects of nasal coadministration of adjuvants , 2004, Immunology and cell biology.

[66]  J. Mcghee,et al.  Effective Mucosal Immunity to Anthrax: Neutralizing Antibodies and Th Cell Responses Following Nasal Immunization with Protective Antigen1 , 2003, The Journal of Immunology.

[67]  M. Pearse,et al.  ISCOMATRIX adjuvant for antigen delivery. , 2005, Advanced drug delivery reviews.

[68]  Z. Moldoveanu,et al.  CpG DNA, a novel immune enhancer for systemic and mucosal immunization with influenza virus. , 1998, Vaccine.

[69]  N. Walters,et al.  M cell-targeted DNA vaccination , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[70]  I. Toth,et al.  Structure-activity relationship of lipopeptide Group A streptococcus (GAS) vaccine candidates on toll-like receptor 2. , 2010, Vaccine.

[71]  P. Mezin,et al.  Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells. , 2007, Vaccine.

[72]  S. Michalek,et al.  Adjuvant Activity of Monophosphoryl Lipid A for Nasal and Oral Immunization with Soluble or Liposome-Associated Antigen , 2000, Infection and Immunity.

[73]  Robyn P. Seipp,et al.  MUCOSAL IMMUNITY AND VACCINES , 2013 .

[74]  K. Mittenbühler,et al.  Bacterial cell wall components as immunomodulators--I. Lipopeptides as adjuvants for parenteral and oral immunization. , 1997, International journal of immunopharmacology.

[75]  L. Lopalco,et al.  Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. , 2011, Immunity.

[76]  S. Rossi,et al.  Characterization of chitosan hydrochloride--mucin rheological interaction: influence of polymer concentration and polymer:mucin weight ratio. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[77]  F. Fang,et al.  Cross-protection against influenza virus infection by intranasal administration of M1-based vaccine with chitosan as an adjuvant. , 2010, Vaccine.

[78]  N. Mishra,et al.  Surface modified liposomes for nasal delivery of DNA vaccine. , 2008, Vaccine.

[79]  R. Glück,et al.  Influenza virosomes are an efficient delivery system for respiratory syncytial virus-F antigen inducing humoral and cell-mediated immunity. , 2002, Vaccine.

[80]  G. Krivtsov,et al.  Chitosan as an adjuvant for parenterally administered inactivated influenza vaccines , 2008, Archives of Virology.

[81]  L. Boon,et al.  Immune adjuvant efficacy of CpG oligonucleotide in cancer treatment is founded specifically upon TLR9 function in plasmacytoid dendritic cells. , 2011, Cancer research.

[82]  I. Jabbal‐Gill Nasal vaccine innovation , 2010, Journal of drug targeting.

[83]  I. Toth,et al.  Immunological Evaluation of Lipopeptide Group A Streptococcus (GAS) Vaccine: Structure-Activity Relationship , 2012, PloS one.

[84]  P. Liljeström,et al.  Vaccination with Recombinant Alphavirus or Immune-Stimulating Complex Antigen Against Respiratory Syncytial Virus1 , 2002, The Journal of Immunology.

[85]  P. Correale,et al.  Efficient delivery of DNA to dendritic cells mediated by influenza virosomes. , 2004, Vaccine.

[86]  R. Cox,et al.  The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine , 2011, Influenza and other respiratory viruses.

[87]  M. Neutra,et al.  Antigen Delivery to Mucosa-Associated Lymphoid Tissues Using Liposomes as a Carrier , 2002, Bioscience reports.

[88]  L. BenMohamed,et al.  Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses , 2002, Immunology.

[89]  S. Rockman,et al.  Intranasal vaccination with ISCOMATRIX adjuvanted influenza vaccine. , 2003, Vaccine.

[90]  Y. Perrie,et al.  Liposomal vaccine delivery systems , 2011, Expert opinion on drug delivery.

[91]  M. Tanner,et al.  Virosome-Formulated Plasmodium falciparum AMA-1 & CSP Derived Peptides as Malaria Vaccine: Randomized Phase 1b Trial in Semi-Immune Adults & Children , 2011, PloS one.

[92]  R. Rappuoli,et al.  A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery. , 2000, Vaccine.

[93]  A. Krieg,et al.  CpG DNA is an effective oral adjuvant to protein antigens in mice. , 2000, Vaccine.

[94]  E. Maraskovsky,et al.  ISCOMATRIX™ adjuvant for prophylactic and therapeutic vaccines , 2007, Expert review of vaccines.

[95]  W. Bessler,et al.  Synthetic lipopeptides as novel adjuvants. , 1992, Research in immunology.

[96]  B. Guy Evaluation of Events Occurring at Mucosal Surfaces: Techniques Used To Collect and Analyze Mucosal Secretions and Cells , 2002, Clinical and Vaccine Immunology.

[97]  I. Toth,et al.  Design of three-component vaccines against group A streptococcal infections: importance of spatial arrangement of vaccine components. , 2010, Journal of medicinal chemistry.

[98]  S. Harding Mucoadhesive interactions. , 2003, Biochemical Society transactions.

[99]  K. Whaley,et al.  Preventing transmission: plant-derived microbicides and mucosal vaccines for reproductive health. , 2005, Vaccine.

[100]  H. Takeuchi,et al.  In vitro and in vivo evaluation of WGA-carbopol modified liposomes as carriers for oral peptide delivery. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[101]  S. Davis,et al.  Chitosan as a novel nasal delivery system for vaccines. , 2001, Advanced drug delivery reviews.

[102]  M. Russell,et al.  Nasal Lymphoid Tissue (NALT) as a Mucosal Immune Inductive Site , 1997, Scandinavian journal of immunology.

[103]  D. Briles,et al.  The Nasal Dendritic Cell-Targeting Flt3 Ligand as a Safe Adjuvant Elicits Effective Protection against Fatal Pneumococcal Pneumonia , 2011, Infection and Immunity.

[104]  C. Ángel Reproductive health , 1999, The Lancet.

[105]  F. Hayden,et al.  The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. , 1998, The New England journal of medicine.

[106]  B. Mishra,et al.  Sodium Alginate Microspheres of Metoprolol Tartrate for Intranasal Systemic Delivery: Development and Evaluation , 2003, Drug delivery.

[107]  G. Perozzi,et al.  The effect of chitosan and other polycations on tight junction permeability in the human intestinal Caco-2 cell line(1). , 2002, The Journal of nutritional biochemistry.

[108]  K. Kedzierska,et al.  Intranasal lipopeptide primes lung‐resident memory CD8+ T cells for long‐term pulmonary protection against influenza , 2006, European journal of immunology.

[109]  A. Nesburn,et al.  A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge , 2009, Mucosal Immunology.

[110]  K. Noda,et al.  Nasal immunization with plasmid DNA encoding P6 protein and immunostimulatory complexes elicits nontypeable Haemophilus influenzae-specific long-term mucosal immune responses in the nasopharynx. , 2011, Vaccine.

[111]  N. Kojima,et al.  Mucosal adjuvant activity of oligomannose-coated liposomes for nasal immunization , 2009, Glycoconjugate Journal.

[112]  C. Hill,et al.  M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis. , 2008, FEMS immunology and medical microbiology.

[113]  S. Koernig,et al.  ISCOMATRIX Adjuvant Combines Immune Activation with Antigen Delivery to Dendritic Cells In Vivo Leading to Effective Cross-Priming of CD8+ T Cells , 2011, The Journal of Immunology.

[114]  J. Wilschut,et al.  Delivery of Protein Antigens to the Immune System by Fusion-Active Virosomes: A Comparison with Liposomes and ISCOMs , 2002, Bioscience reports.

[115]  R. Coler,et al.  Taking toll: lipid A mimetics as adjuvants and immunomodulators. , 2002, Trends in microbiology.

[116]  P. Kozlowski,et al.  Mucosal vaccines: the promise and the challenge , 2006, Nature Reviews Immunology.