title: Co-vaccination with adeno-associated virus vectors encoding human papillomavirus 16 L1 proteins and adenovirus encoding murine GM-CSF can elicit strong and prolonged neutralizing antibody.
abstract: Non-infectious human papillomavirus-like particles (VLPs), encoded by the major capsid gene L1, have been shown to be effective as vaccines to prevent cervical cancer. We have developed the genetic immunization of the L1 gene to induce a neutralizing antibody. We constructed and generated a recombinant adeno-associated virus encoding human papillomavirus (HPV) 16 L1 protein that could form virus-like particles in transduced cells. Previous reports have demonstrated that the formation of VLP is necessary to induce high titers of neutralizing antibodies to protect an animal from viral challenge. Therefore, we carried out a single intramuscular (i.m.) injection with recombinant adeno-associated virus encoding HPV-16 L1 protein (rAAV-16L1) in BALB/c mice, which ultimately produced stronger and more prolonged neutralizing L1 antibodies, when compared to the DNA vaccine. Immunohistochemistry showed that the accumulation of antigen presenting cells, such as macrophages and dendritic cells, in rAAV-16L1 and L1 DNA-injected muscle fibers may be due to the L1 protein expression, but not to AAV infection. When compared to the L1 VLP vaccine, however, the titers of neutralizing L1 antibodies induced by VLP were higher than those induced by rAAV-16L1. Co-vaccinating with rAAV-16L1 and adenovirus encoding murine GM-CSF (rAAV-16L1/rAd-mGM-CSF) induced comparable higher levels of neutralizing L1 antibodies with those of VLP. This implies that a single i.m. co-injection with rAAV-16L1/rAd-mGM-CSF can achieve the same vaccine effect as a VLP vaccine requiring 3 booster injections.
authors.affiliation: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Dai-Wei
authors.initials: DW
authors.lastname: Liu
authors.forename: Junn-Liang
authors.initials: JL
authors.lastname: Chang
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Huang
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Kuo
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000938:Antigen-Presenting Cells; D002213:Capsid; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D000229:Dependovirus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D006386:Hemagglutination Tests; D007117:Immunization, Secondary; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C063317:L1 protein, Human papillomavirus type 16; D016178:Granulocyte-Macrophage Colony-Stimulating Factor