Associate Professor Hans J Netter - Lecturer

Contact Details

Telephone: +61 3 9902 9191
Fax: +61 3 9902 9222
email: hans.netter@med.monash.edu.au

Laboratory Personnel

Dr Wan-Shoo Cheong (Research Fellow)
    e-mail: wan.cheong@med.monash.edu.au
    Phone:  (+61) (03) 9902 9180

Ms Michiko Hyakumura (PhD student)
    e-mail: michiko.hyakumura@med.monash.edu.au
   Phone:  (+61) (03) 9902 9199

Ms ShanShan Li (Student, Master of Biomedical Science, Part 1)
    e-mail: shanshan.li@med.monash.edu.au 
    Phone:  (+61) (03) 9902 9199

Telephone (laboratory): +61 3 9902 9203

Summary of the research interests

Development of chimeric virus-like particles as vaccination tools and assessment of their mode of action

Virus-like particles (VLPs) are successfully used as vaccines for the prevention of infections against hepatitis B virus (HBV) and human papilloma virus (HPV). VLPs represent an effective vaccine modality as they are highly immunogenic due to their spatial and repeated sub-unit structure providing epitopes in several copies on a defined particle. The small hepatitis B surface (envelope) antigen (HBsAg) has the capacity to self-assemble with host-derived lipids into empty spheres of 22nm in diameter (Figure 1), and they are the sole antigenic component of one of the most successful vaccine (hepatitis B). Clinical trials have also shown that they are highly successful delivery systems for foreign epitopes and protein domains. The ability of VLPs to serve as carriers of B cell and cytotoxic T lymphocyte (CTL) epitopes derived from either the parental virus or foreign sources has enhanced their potential as prophylactic and therapeutic vaccines. Objectives aim to design chimeric VLPs with the capacity to induce protective immune responses, and to learn about their mode of action. Chimeric HBsAg VLPs are generated by introducing antigenic sequences derived from various pathogens with unmet medical need, and immunisation studies are applied to determine the quality of the immune response at the level of the innate and adaptive immune system.

Figure 1: Identification of purified HBsAg VLPs by electron microscopy. Panel A: VLPs derived from serum of a chronic HBV carrier; Panel B: cell culture derived chimeric VLPs containing a hepatitis C virus-specific sequence. Bar: 100nm.

Assembly of hepatitis delta virus (HDV) in the presence of mutant HBV envelope proteins

Hepatitis delta virus (HDV) is a satellite virus, which requires the presence of HBV to provide HBsAg envelope proteins for viral assembly and secretion. The presence of HDV can contribute to the development of severe chronic and acute hepatitis in humans. To gain a detailed understanding of the HBsAg and HDV secretion process, mutant HBsAg proteins are investigated regarding their ability to form particulate structures, which allow the envelopment of HDV-specific components and the generation of HDV particles. In particular, differential efficiencies of mutant HBsAg proteins expressed by drug-resistant HBV to support HDV secretion may have consequences for clinical prognosis as HDV and HBV co-infected patients are treated with antiviral agents.

Selected list of publications:

Cheong W-S., Reiseger J., Turner S.J., Boyd R., and Netter H.J. (2009) Chimeric virus-like particles for the delivery of an inserted conserved influenza A-specific CTL epitope. Antiviral Res. 81: 113-122.

Cheong W-S., Drummer H.E., and Netter H.J. (2009) Delivery of a foreign epitope by sharing amino acid residues with the carrier matrix. J. Virol. Methods 158: 35-40.

Netter H.J., Chang S-F., and Bruns M. (2008) Host-range and pathogenicity of hepatitis B viruses. Future Virology 3: 83-94.

Vietheer P.T.K., Boo I., Drummer H.E., and Netter H.J. (2007) Immunisations with chimeric hepatitis B virus-like particles (VLPs) to induce potential anti-hepatitis C virus (HCV) neutralising antibodies. Antiviral Therapy 12: 477-487.

Woo W-P., Doan T., Herd K.A., Netter H.J., and Tindle R.W. (2006) Hepatitis B surface antigen (HBsAg) vector delivers protective CTL responses to disease-relevant foreign epitopes. J. Virology 80: 3975-3984. [HJN and RWT, joint senior authors]

Vietheer P.T.K., Netter H.J., Sozzi T., and Bartholomeusz A. (2005) Failure of the lamivudine-resistant rtM204I hepatitis B virus mutants to efficiently support hepatitis delta virus secretion. J. Virology 79: 6570-6573.

Chang S.-F., Chang S.-H., Li B.-C., Will H., and Netter H.J. (2004) Characterization of nonconventional hepatitis B viruses lacking the core promoter. Virology 330, 437-446.

Netter H.J., Woo W.-P., Tindle R., Macfarlan R.I., and Gowans E.J. (2003) Immunogenicity of recombinant HBsAg/HCV particles in mice pre-immunised with hepatitis B virus-specific vaccine. Vaccine 21, 2692-2697.