Journal article

Sindbis virus vectors elicit hemagglutinin-specific humoral and cellular immune responses and offer a dose-sparing strategy for vaccination

A Miller, RJ Center, J Stambas, G Deliyannis, PC Doherty, JL Howard, SJ Turner, DFJ Purcell

Vaccine | ELSEVIER SCI LTD | Published : 2008

Abstract

We report here on the use of a Sindbis virus-based DNA-launch RNA replicon vector (pSIN-HA) that expresses influenza hemagglutinin (HA) as an immunogen. Immunization of mice with pSIN-HA generated anti-HA antibody and CTL responses and resulted in lower lung viral titers after influenza challenge when compared to controls. Importantly, immunization with a low dose of pSIN-HA mediated significantly reduced lung viral titers following challenge at 43 weeks after the final immunization. In contrast, immunization with a non-replicon DNA vector expressing HA failed to mediate reduced lung viral titer at the same dose. This demonstrated the dose-sparing capacity of the SIN vector system and its ab..

View full abstract

Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia through a program grant (299907) to PCD and R.D. Wright Fellowships to RJC and SJT. The p987SINrep5 and pSIN-GFP vectors were kindly provided by Dr. Sondra Schlesinger (Washington University, St. Louis, USA). PR8 virus for PR8 immunization or challenge, rabbit polyclonal anti-HA serum and the monoclonal antibody E2.6 were provided by Dr. L.E. Brown, Department of Microbiology and Immunology, University of Melbourne, Australia, and inactivated PR8 virus for ELISA was provided by Ian Barr (World Health Organization Collaborating Centre for Reference and Research on Influenza, Parkville, Australia).