Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

Abstract

INTRODUCTION:

RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2) ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine.

OBJECTIVE:

To explore if intranasal (IN) immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity.

METHODS:

We produced RSV-virosomes carrying TLR2 (Pam3CSK4) and/or NOD2 (L18-MDP) ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice.

RESULTS:

Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting) cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced disease.

CONCLUSION:

Mucosal immunization with RSV-virosomes, supplemented with incorporated TLR2- and/or NOD2-ligands, represents a promising approach to induce effective and safe RSV-specific immunity.

• Authors: Muhammad Shafique, Tjarko Meijerhof, Jan Wilschut, Aalzen de Haan
• Journal: PloS one (PLoS One) Vol. 8 Issue 4 Pg. e61287 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23593453 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Nod2 Signaling Adaptor Protein
• Nod2 protein, mouse
• Tlr2 protein, mouse
• Toll-Like Receptor 2
• Vaccines, Virosome

Topics

• Administration, Intranasal
• Animals
• Cell Line
• Female
• Humans
• Immunity, Mucosal (immunology)
• Ligands
• Lung (immunology, pathology, virology)
• Mice
• Nod2 Signaling Adaptor Protein (metabolism)
• Respiratory Syncytial Viruses (immunology, physiology)
• Species Specificity
• Toll-Like Receptor 2 (metabolism)
• Vaccines, Virosome (adverse effects, immunology)