In vivo mechanisms of vaccine-induced protection against HPV infection.
Using a human papillomavirus (HPV) cervicovaginal murine challenge model, we microscopically examined the in vivo mechanisms of L1 virus-like particle (VLP) and L2 vaccine-induced inhibition of infection. In vivo HPV infection requires an initial association with the acellular basement membrane (BM) to induce conformational changes in the virion that permit its association with the keratinocyte cell surface. By passive transfer of immune serum, we determined that anti-L1 antibodies can interfere with infection at two stages. Similarly to active VLP immunization, transfer of high L1 antibody concentrations prevented BM binding. However, in the presence of low concentrations of anti-L1, virions associated with the BM, but to the epithelial cell surface was not detected. Regardless of the concentration, L2 vaccine-induced antibodies allow BM association but prevent association with the cell surface. Thus, we have revealed distinct mechanisms of vaccine-induced inhibition of virus infection in vivo.
Day
Patricia M
PM
Laboratory of Cellular Oncology, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892, USA.
Kines
Rhonda C
RC
Thompson
Cynthia D
CD
Jagu
Subhashini
S
Roden
Richard B
RB
Lowy
Douglas R
DR
Schiller
John T
JT
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001485:Basement Membrane / Q000821:virology; D036022:Capsid Proteins / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D052162:Human papillomavirus 16 / Q000276:immunology*; D007116:Immunization, Passive; D015603:Keratinocytes / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000276:immunology*; D010957:Plasmids; D014611:Vaccination; D014621:Vagina / Q000821:virology
D000914:Antibodies, Viral; D036022:Capsid Proteins; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; C063317:L1 protein, Human papillomavirus type 16