TY - JOUR
T1 - In vivo mechanisms of vaccine-induced protection against HPV infection
AU - Day, Patricia M.
AU - Kines, Rhonda C.
AU - Thompson, Cynthia D.
AU - Jagu, Subhashini
AU - Roden, Richard B.
AU - Lowy, Douglas R.
AU - Schiller, John T.
N1 - Funding Information:
D.R.L. and J.T.S. are inventors of intellectual property owned by the US government for the L1 vaccine. D.R.L., J.T.S., S.J. and R.B.R. are inventors of intellectual property owned by the US government and Johns Hopkins University for the L2 vaccine. R.B.R. has been a paid consultant of Merck & Co, Inc., and both S.J. and R.B.R. have received unrestricted educational grant funding from GlaxoSmithKline. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies.
Funding Information:
This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and by National Cancer Institute, SPORE in Cervical Cancer, P50 CA098252 and CA118790 to R.B.R. and a Prevent Cancer Foundation, Alexandria, VA fellowship to S.J.
PY - 2010/9/16
Y1 - 2010/9/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2010.08.003
DO - 10.1016/j.chom.2010.08.003
M3 - Article
C2 - 20833377
AN - SCOPUS:77956570980
SN - 1931-3128
VL - 8
SP - 260
EP - 270
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -