Immunization with a pentameric L1 fusion protein protects against papillomavirus infection.
The prophylactic papillomavirus vaccines currently in clinical trials are composed of viral L1 capsid protein that is synthesized in eukaryotic expression systems and purified in the form of virus-like particles (VLPs). To evaluate whether VLPs are necessary for effective vaccination, we expressed the L1 protein as a glutathione S-transferase (GST) fusion protein in Escherichia coli and assayed its immunogenic activity in an established canine oral papillomavirus (COPV) model that previously validated the efficacy of VLP vaccines. The GST-COPV L1 fusion protein formed pentamers, but these capsomere-like structures did not assemble into VLPs. Despite the lack of VLP formation, the GST-COPV L1 protein retained its native conformation as determined by reactivity with conformation-specific anti-COPV antibodies. Most importantly, the GST-COPV L1 pentamers completely protected dogs from high-dose viral infection of their oral mucosa. L1 fusion proteins expressed in bacteria represent an economical alternative to VLPs as a human papillomavirus vaccine.
Yuan
H
H
Department of Pathology, Georgetown University School of Medicine, Washington, DC 20007, USA.
Estes
P A
PA
Chen
Y
Y
Newsome
J
J
Olcese
V A
VA
Garcea
R L
RL
Schlegel
R
R
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009055:Mouth / Q000821:virology; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014412:Tumor Virus Infections / Q000517:prevention & control*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D005982:Glutathione Transferase