Chimeric virus-like particles for the delivery of an inserted conserved influenza A-specific CTL epitope

• Published in: Antiviral research 2009-02, Vol.81 (2), p.113-122
• Main Authors: Cheong, Wan-Shoo, Reiseger, Jessica, Turner, Stephen John, Boyd, Richard, Netter, Hans-Jürgen
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Cytokines - secretion; Cytotoxicity Tests, Immunologic; Epitopes, T-Lymphocyte - immunology; Female; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus envelope protein; Human viral diseases; Immunologic Memory; Infectious diseases; Influenza A virus - genetics; Influenza A-specific epitope; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Influenza virus; Lymphocyte Subsets - immunology; Male; Medical sciences; Mice; Mice, Transgenic; Modified virus-like particles; Orthomyxoviridae Infections - immunology; Pharmacology. Drug treatments; Vaccination study; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Viral hepatitis; Viral Matrix Proteins - genetics; Viral Matrix Proteins - immunology; Virosomes - genetics; Virosomes - immunology
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2008.10.003

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.