Chimeric virus-like particles for the delivery of an inserted conserved influenza A-specific CTL epitope.
The small hepatitis B virus surface antigens (HBsAg-S) have the ability to self-assemble with host-derived lipids into empty non-infectious virus-like particles (VLPs). HBsAg-S VLPs are the sole component of the licensed hepatitis B vaccine, and they are a useful delivery platform for foreign epitopes. To develop VLPs capable of transporting foreign cytotoxic T lymphocyte (CTL) epitopes, HBsAg-S specific CTL epitopes at various sites were substituted with a conserved CTL epitope derived from the influenza matrix protein. Depending on the insertion site, the introduction of the MHC class I A2.1-restricted influenza epitope was compatible with the secretion competence of HBsAg-S indicating that chimeric VLPs were assembled. Immunizations of transgenic HHDII mice with chimeric VLPs induced anti-influenza CTL responses proving that the inserted foreign epitope can be correctly processed and cross-presented. Chimeric VLPs in the absence of adjuvant were able to induce memory T cell responses, which could be recalled by influenza virus infections in the mouse model system. The ability of chimeric HBsAg-S VLPs to induce anti-foreign CTL responses and also with the proven ability to induce humoral immune responses constitute a highly versatile platform for the delivery of selected multiple epitopes to target disease associated infectious agents.
Cheong
Wan-Shoo
WS
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Reiseger
Jessica
J
Turner
Stephen John
SJ
Boyd
Richard
R
Netter
Hans-Jürgen
HJ
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D007156:Immunologic Memory; D009980:Influenza A virus / Q000235:genetics; D007252:Influenza Vaccines / Q000235:genetics* / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D022701:Virosomes / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins; D022701:Virosomes