A virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A provides protection against viral challenge without priming for enhanced disease in cotton rats

Tobias Kamphuis, Toon Stegmann, Tjarko Meijerhof, Jan Wilschut, Aalzen de Haan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
163 Downloads (Pure)

Abstract

Background Non-replicating respiratory syncytial virus (RSV) vaccine candidates could potentially prime for enhanced respiratory disease (ERD) due to a T-cell-mediated immunopathology, following RSV infection. Vaccines with built-in immune response modifiers, such as Toll-like receptor (TLR) ligands, may avoid such aberrant imprinting of the immune system.

Methods We developed reconstituted RSV envelopes (virosomes) with incorporated TLR4 ligand, monophosphoryl lipid A (RSV-MPLA virosomes). Immune responses and lung pathology after vaccination and challenge were investigated in ERD-prone cotton rats and compared with responses induced by live virus and formaldehyde-inactivated vaccine (FI-RSV), a known cause of ERD upon RSV challenge.

Results Vaccination with RSV-MPLA virosomes induced higher levels of virus-neutralizing antibodies than FI-RSV or live virus infection and provided protection against infection. FI-RSV, but not RSV-MPLA virosomes, primed for increases in expression of Th2 cytokines IL-4, IL-5, IL-13, and Th1 cytokine IL-1b, 6 hour-5 days after infection. By contrast, RSV-MPLA virosomes induced IFN-gamma transcripts to similar levels as induced by live virus. Animals vaccinated with FI-RSV, but not RSV-MPLA virosomes showed alveolitis, with prominent neutrophil influx and peribronchiolar and perivascular infiltrates.

Conclusion These results show that RSV-MPLA virosomes represent a safe and immunogenic vaccine candidate that warrants evaluation in a clinical setting.

Original languageEnglish
Pages (from-to)1227-1236
Number of pages10
JournalInfluenza and other respiratory viruses
Volume7
Issue number6
DOIs
Publication statusPublished - Nov-2013

Keywords

  • Adjuvant
  • cotton rat
  • enhanced respiratory disease
  • monophosphoryl lipid A
  • respiratory syncytial virus
  • vaccine
  • virosomes
  • FORMALIN-INACTIVATED VIRUS
  • INFECTIOUS-DISEASES
  • ANTIBODY-RESPONSES
  • RECEPTOR
  • IMMUNIZATION
  • CELLS
  • ANAPHYLATOXIN
  • GLYCOPROTEIN
  • EXPRESSION
  • CHILDREN

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