Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine

Lissette S. Velasquez, Samantha Shira, Alice N. Berta, Jacquelyn Kilbourne, Babu M. Medi, Ian Tizard, Yawei Ni, Charles J. Arntzen, Melissa Herbst-Kralovetz

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling Norwalk virus-like particles (NV VLPs) delivered enterically or at nasal surfaces. Nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. Herein, we describe the use of a dry powder formulation (GelVac) of an inert in situ gelling polysaccharide (GelSite) extracted from Aloe vera for nasal delivery of NV VLP antigen. Powder formulations, with or without NV VLP antigen, were similar in structure in dry form or when rehydrated in simulated nasal fluids. Immunogenicity of the dry powder VLP formulation was compared to equivalent antigen/adjuvant liquid formulations in animals. For the GelVac powder, we observed superior NV-specific serum and mucosal (aerodigestive and reproductive tracts) antibody responses relative to liquid formulations. Incorporation of the TLR7 agonist gardiquimod in dry powder formulations did not enhance antibody responses, although its inclusion in liquid formulations did enhance VLP immunogenicity irrespective of the presence or absence of GelSite. We interpret these data as showing that GelSite-based dry powder formulations (1) stabilize the immunogenic structural properties of VLPs and (2) induce systemic and mucosal antibody titers which are equal or greater than those achieved by VLPs plus adjuvant in a liquid formulation. We conclude that in situ gelation of the GelVac dry powder formulation at nasal mucosal surfaces delays mucociliary clearance and thereby prolongs VLP antigen exposure to immune effector sites.

Original languageEnglish (US)
Pages (from-to)5221-5231
Number of pages11
JournalVaccine
Volume29
Issue number32
DOIs
StatePublished - Jul 18 2011

Fingerprint

Norwalk virus
virus-like particles
gelation
Virion
Powders
powders
Vaccines
Nose
vaccines
antigens
Antigens
Mucociliary Clearance
Immunization
immunization
liquids
immune response
adjuvants
antibodies
Antibody Formation
Aloe

Keywords

  • Intranasal delivery
  • Mucoadhesive
  • Norovirus vaccine
  • Spray dry powder formulation
  • TLR agonist
  • Virus-like particles (VLP)

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine. / Velasquez, Lissette S.; Shira, Samantha; Berta, Alice N.; Kilbourne, Jacquelyn; Medi, Babu M.; Tizard, Ian; Ni, Yawei; Arntzen, Charles J.; Herbst-Kralovetz, Melissa.

In: Vaccine, Vol. 29, No. 32, 18.07.2011, p. 5221-5231.

Research output: Contribution to journalArticle

Velasquez, LS, Shira, S, Berta, AN, Kilbourne, J, Medi, BM, Tizard, I, Ni, Y, Arntzen, CJ & Herbst-Kralovetz, M 2011, 'Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine', Vaccine, vol. 29, no. 32, pp. 5221-5231. https://doi.org/10.1016/j.vaccine.2011.05.027
Velasquez LS, Shira S, Berta AN, Kilbourne J, Medi BM, Tizard I et al. Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine. Vaccine. 2011 Jul 18;29(32):5221-5231. https://doi.org/10.1016/j.vaccine.2011.05.027
Velasquez, Lissette S. ; Shira, Samantha ; Berta, Alice N. ; Kilbourne, Jacquelyn ; Medi, Babu M. ; Tizard, Ian ; Ni, Yawei ; Arntzen, Charles J. ; Herbst-Kralovetz, Melissa. / Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine. In: Vaccine. 2011 ; Vol. 29, No. 32. pp. 5221-5231.
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