Open AccessA virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A provides protection against viral challenge without priming for enhanced disease in cotton rats
Author(s) -
Kamphuis Tobias,
Stegmann Toon,
Meijerhof Tjarko,
Wilschut Jan,
Haan Aalzen
Publication year - 2013
Publication title -
influenza and other respiratory viruses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.743
H-Index - 57
eISSN - 1750-2659
pISSN - 1750-2640
DOI - 10.1111/irv.12112
Subject(s) - immune system , immunology , virus , virology , vaccination , medicine , biology
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 T oll‐like receptor ( TLR ) ligands, may avoid such aberrant imprinting of the immune system. Methods We developed reconstituted RSV envelopes (virosomes) with incorporated TLR 4 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 T h2 cytokines IL ‐4, IL ‐5, IL ‐13, and T h1 cytokine IL ‐1b, 6 hour–5 days after infection. By contrast, RSV ‐ MPLA virosomes induced IFN ‐γ 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.