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. Author manuscript; available in PMC: 2019 Jan 1.
Published in final edited form as: Eur J Pharm Biopharm. 2017 Nov 6;122:167–175. doi: 10.1016/j.ejpb.2017.11.001

Table 1.

Intranasal dry powder vaccines tested in vivo.

Disease Antigen Method of production Adjuvant Other excipients Device Model Findings References
Diphtheria CRM197 formaldehyde treated
(50 μg/dose)		 N/S Chitosan and mannitol Monopowder (Valois) Human
  • ·

    IgA and IgG serum levels: Equivalent to IM immunization

 (Mills et al., 2003)
CRM197 formaldehyde treated
(50 μg/dose)		 N/S Chitosan, phosphate salts, and mannitol Monopowder (Valois) Human
  • ·

    First study to demonstrate systemic T cell subtype response induced by a nasal vaccine

 (McNeela et al., 2004)
Influenza Whole inactivated virus strain H1N1
(100 μg/dose)		 FD Chitosan and trehalose Plastic housing unit attached to a syringe (WO 2002055133 A3) Rat
  • ·

    Stability: Higher stability than liquid vaccine after 12 weeks of storage at 25 °C.

  • ·

    IgA and IgG serum levels: Equivalent to IM and liquid IN immunization

 (Huang et al., 2004)
Whole inactivated virus strain H1N1
(5 μg/dose)		 SFD Chitosan, trehalose, HPMC-HMW, CMC-HMW and SA. Lab-made device Rat
  • ·

    Stability: Higher stability than liquid vaccine after 12 weeks of storage at 25 °C.

  • ·

    Mucoadhesives: SA and CMC-HMW increased the residence time

  • ·

    IgA and IgG serum levels: Equivalent to IM and liquid IN immunization

 (Garmise et al., 2007)
Whole heat-inactivated virus strain H3N2
(50 μg/dose)		 FD LTR192G Starch and polyacrylic acid Lab-made device Rabbit
  • ·

    Evaluation of different mucoadhesives ratios.

  • ·

    IgG serum levels: Correlated with the polyacrylic acid content.

  • ·

    sIgA nasal levels: Not detected.

 (Coucke et al., 2009)
Whole UV-inactivated virus strain H1N1
(45 μg/dose)		 Nanoencapsulation CpG or Quillaja saponin Chitosan Lab-made device Rabbit
  • ·

    Evaluation of different adjuvants.

  • ·

    All DPV formulations were equal or better than IM vaccination.

  • ·

    IgG serum levels: Highest values obtained with CpG.

  • ·

    sIgA nasal levels: Highest values obtained with CpG.

 (Dehghan et al., 2014)
Meningitis Meningococcal C oligosaccharide-CRM197 conjugated
(10 μg/dose)		 N/S Chitosan Combitips plus® (Eppendorf) Human
  • ·

    IgA and IgG serum levels: Equivalent to IM immunization.

  • ·

    sIgA nasal levels: Restricted to the immunized side.

 (Huo et al., 2005)
Anthrax rPA
(50 μg/dose)		 FD or SFD CpG Chitosan and trehalose Plastic housing unit attached to a syringe (WO 2002055133 A3) Rabbit
  • ·

    Evaluation of different administration routes (IM, ID, IN, and topical) and drying methods.

  • ·

    IgG serum levels: Highest with SFD

  • ·

    % survival after anthrax challenge: Equivalent to IM immunization (100%) and higher than liquid IN group (67%).

 (Mikszta et al., 2005)
rPA
(10 μg/dose)		 SFD CpG Chitosan and trehalose Plastic housing unit attached to a syringe (WO 2002055133 A3) Rabbit
  • ·

    Lower dose than in a previous study.

  • ·

    IgG serum levels: Lower than IM but equivalent to liquid IN immunization.

  • ·

    % survival after anthrax challenge: Higher than IM (86%) and liquid IN (63%) immunizations.

 (Huang et al., 2007)
rPA (90 μg/dose) combined with free capsule peptide (18 μg/dose) or with rPA- conjugate (90 μg/dose) FD MPL Chitosan and mannitol Monopowder (Valois) Rabbit
  • ·

    Evaluation of different antigens and effect of chitosan.

  • ·

    Anti-rPA IgG serum levels: DPVs containing chitosan were equivalent to IM and higher than liquid IN immunization.

  • ·

    Anti-capsule IgG serum levels: Only observed when the peptide was conjugated to rPA and where equivalent with or without chitosan.

  • ·

    Eating behavior after anthrax challenge: Anorexic behavior in rPA + free peptide group compared to normal behavior in rPA + rPA− conjugate group.

 (Wimer-Mackin et al., 2006)
rPA (50–150 μg/dose) alone or combined with BSA-conjugate (150 μg/dose) FD MPL Chitosan and mannitol Monopowder (Valois) Rabbit
  • ·

    Evaluation of different doses and antigens.

  • ·

    Anti-rPA IgG serum levels: All DPV were equivalent and lower than IM immunization after 3 weeks, but higher after 6 weeks.

  • ·

    % survival after anthrax challenge: Higher in the rPA + BSA-conjugate group (80%) than and rPA alone group (60%).

 (Klas et al., 2008)
rPA (30 μg/dose) SFD C48/80 Trehalose Unit-dose system (Aptar) Rabbit
  • ·

    Stability: Higher stability than liquid vaccine after 90 days at 25 °C. DPV maintained its activity after 2 years.

  • ·

    IgG serum levels: Equivalent to IM and liquid IN immunization.

 (Wang et al., 2012)
Tetanus Tetanus toxoid (40 Lf/dose) Microencapsulation Quillaja saponin Alginate and cross-linked dextran Lab-made Rabbit
  • ·

    Evaluation of different excipients.

  • ·

    IgG serum levels: Equivalent between DPVs but lower than IM immunization.

  • ·

    sIgA nasal levels: Equivalent between DPVs and higher than IM immunization. Highest level observed when cross-linked dextran was included.

 (Tafaghodi and Rastegar, 2010)
Gastroenteritis Norovirus virus-like particles (GI.1)
(10 μg/dose)		 SD Gardiquimod GelSite® Lab-made Guinea pig
  • ·

    Evaluation of the sIgA and sIgG levels in different mucosal surfaces after IN immunization: Significantly higher levels using GelSite®.

  • ·

    IgG serum levels: Highest values observed after 6 weeks with GelSite®.

 (Velasquez et al., 2011)
Norovirus virus-like particles GI and GII.4
(0.1–100 μg/dose)		 FD GelSite® Unit-dose system (Aptar) Guinea pig
  • ·

    Evaluation of different doses of two monovalent DPVs.

  • ·

    IgG serum and sIgG vaginal levels: Significantly higher values observed above 15 μg/dose in both DPVs.

  • ·

    IgA serum levels: Equivalent at all concentrations of both DPVs.

 (Springer et al., 2016)
Norovirus virus-like particles GI and GII.4 (5100 μg/dose) FD GelSite® Unit-dose system (Aptar) Guinea pig
  • ·

    Evaluation of different doses of a bivalent DPV.

  • ·

    IgG serum and sIgG vaginal levels: Dose-dependent response for both antigens. Highest values observed 3 weeks after the second dose.

  • ·

    IgG intestinal leve ls: Dose-dependent response up to 50 ug/dose.

 (Ball et al, 2017)
Norovirus virus-like particles (GI.1) (5–100 μg/dose) FD MPL Chitosan, sucrose, and mannitol UniDose DP (Bespak) Human
  • ·

    Phase 1 clinical studies

  • ·

    Common adverse events: Nasal stuffiness and discharge.

  • ·

    IgA serum levels: Response observed above 50 μg/dose

  • ·

    IgG serum levels: Response observed above 15 μg/dose

 (El-Kamary et al., 2010)
Norovirus virus-like particles (GI.1) (50–100 μg/dose) FD MPL Chitosan, sucrose, and mannitol UniDose DP (Bespak) Human
  • ·

    Phase 1 clinical studies

  • ·

    B memory cell population: above 4-fold increase in expression of CD27+ and CD38+

  • ·

    IgA and IgG B memory response: In 100% of patients receiving 100 μg/dose and 90% of patients receiving 50 μg/dose.

 (El-Kamary et al., 2010, Ramirez et al., 2012)
Norovirus virus-like particles (GI.1)
(100 μg/dose)		 FD MPL Chitosan, sucrose, and mannitol UniDose DP (Bespak) Human
  • ·

    Phase 1 and 2 clinical studies

  • ·

    Common adverse events: Nasal stuffiness and discharge.

  • ·

    Norwalk virus challenge: Significantly lower infection (61%) and illness (37%) compared to placebo (82% and 69%, respectively).

 (Atmar et al., 2011)

CRM197: cross-reacting material of the diphtheria toxin; FD: Freeze-drying; IN: intranasal; IM: intramuscular; SFD: Spray-freeze drying; HPMC-HMW: Hydroxypropyl methylcellulose, high molecular weight; CMC-HMW: Carboxymethylcellulose sodium, high molecular weight; SA: Sodium alginate; LTR192G: Heat-labile enterotoxin R192G mutant; rPA: recombinant Protective Antigen of B. anthracis; ID: intradermal; rPA conjugate; Capsule peptide conjugated to rPA; MPL: Monophosphoryl lipid A; BSA-conjugate: Capsule peptide conjugated to bovine serum albumin; GelSite®: Aloe vera derived polysaccharide polymer; Lf: Flocculation units; N/S: not specified