A chimaeric plant virus vaccine protects mice against a bacterial infection

1 Axis Genetics plc, Babraham, Cambridge CB2 4AZ, UK 2 Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine in Shreveport, Shreveport, LA 71130-3932, USA Author for correspondence: William D. O. Hamilton. Tel: +44 1223 837611. Fax: +44 1223 837604. e-mail: hamiltonw@axisgenetics.co.uk ABSTRACT The plant virus cowpea mosaic virus (CPMV) is an efficient carrier of foreign peptides for the generation of strong humoral immune responses. Peptides derived from both viruses and bacteria are strongly immunogenic when displayed on the surface of CPMV and elicit high titres of peptide-specific antibody. However, the protective effects of antibodies generated using bacterial epitopes in this system have yet to be demonstrated. In this study the ability of chimaeric virus particles (CVPs) to afford protection against bacterial infection was assessed. Immunization of outbred mice with CPMV expressing a peptide derived from outer-membrane protein F of Pseudomonas aeruginosa (CPMV-PAE5) generated high titres of P. aeruginosa -specific IgG that opsonized the bacteria for phagocytosis by human neutrophils and afforded protection upon challenge with two different immunotypes of P. aeruginosa in a model of chronic pulmonary infection. When examined 8 d after challenge, CVP-immunized mice had fewer severe lung lesions and fewer bacteria in their lungs compared to mice immunized with wild-type virus. Different levels of protection were seen with CPMV-PAE5 when Freund's or alum adjuvants were used. These studies highlight the ability of CVPs to generate protective immunity against infectious disease agents. Keywords: cowpea mosaic virus, chimaeric virus particle, Pseudomonas aeruginosa , outer-membrane protein F, vaccine Abbreviations: CF, cystic fibrosis; CPMV, cowpea mosaic virus; CVP, chimaeric virus particle; FCA, Freund's complete adjuvant; FD, Fisher-Devlin; FIA, Freund's incomplete adjuvant; KLH, keyhole limpet haemocyanin; NMS, normal mouse serum; OM, outer membrane; PMN, polymorphonuclear leucocyte; wt, wild-type.