Comparison of adjuvants for a spray freeze-dried whole inactivated virus influenza vaccine for pulmonary administration

Harshad P. Patil, Senthil Murugappan, Jacobje de Vries-Idema, Tjarko Meijerhof, Aalzen de Haan, Henderik W. Frijlink, Jan Wilschut, Wouter L. J. Hinrichs, Anke Huckriede*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Stable vaccines administered to the lungs by inhalation could circumvent many of the problems associated with current immunizations against respiratory infections. We earlier provided proof of concept in mice that pulmonary delivered whole inactivated virus (WIV) influenza vaccine formulated as a stable dry powder effectively elicits influenza-specific antibodies in lung and serum. Yet, mucosal IgA, considered particularly important for protection at the site of virus entry, was poorly induced. Here we investigate the suitability of various Toll-like receptor (TLR) ligands and the saponin-derived compound GPI-0100 to serve as adjuvant for influenza vaccine administered to the lungs as dry powder. The TLR ligands palmitoyl-3-cysteine-serine-lysine-4 (Pam(3)CSK(4)), monophosphoryl lipid A (MPLA) and CpG oligodeoxynucleotides (CpG ODN) as well as GPI-0100 tolerated the process of spray freeze-drying well. While Pam(3)CSK(4) had no effect on systemic antibody titers, all the other adjuvants significantly increased influenza-specific serum and lung IgG titers. Yet, only GPI-0100 also enhanced mucosal IgA titers. Moreover, only GPI-0100-adjuvanted WIV provided partial protection against heterologous virus challenge. Pulmonary immunization with GPI-0100-adjuvanted vaccine did not induce an overt inflammatory response since influx of neutrophils and production of inflammatory cytokines were moderate and transient and lung histology was normal. Our results indicate that a GPI-0100-adjuvanted dry powder influenza vaccine is a safe and effective alternative to current parenteral vaccines. 

Original languageEnglish
Pages (from-to)231-241
Number of pages11
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume93
DOIs
Publication statusPublished - Jun-2015

Keywords

  • Whole inactivated virus
  • Pulmonary vaccination
  • Spray freeze-drying
  • Adjuvants
  • TOLL-LIKE RECEPTORS
  • RESPIRATORY-TRACT
  • MUCOSAL IMMUNITY
  • CROSS-PROTECTION
  • SUBUNIT VACCINE
  • INNATE IMMUNITY
  • T-CELLS
  • DELIVERY
  • IMMUNIZATION
  • RESPONSES

Cite this