Effect of preexisting neutralizing antibodies on the anti-tumor immune response induced by chimeric human papillomavirus virus-like particle vaccines.

Abstract	Chimeric human papillomavirus virus-like particles (HPV cVLPs) carrying HPV16 E7 protein are potent vaccines for inducing cell-mediated immunity (CMI) against HPV-induced tumors in animal models. We tested the hypothesis that virion-neutralizing antibodies generated during an initial vaccination might prevent effective boosting of CMI to the cVLPs. Mice with circulating HPV16-neutralizing antibodies, generated by direct immunization with wild-type VLPs or by passive transfer of hyperimmune anti-HPV16 VLP mouse sera, were subsequently vaccinated with HPV16 E7-containing cVLPs. Mice with preexisting neutralizing antibodies were not protected from HPV16 E7-positive TC-1 tumor challenge, compared to the protection seen in mice lacking these antibodies. Antibody-coated VLPs bound very inefficiently to receptor-positive cell lines, suggesting that one of the mechanisms of antibody interference is blocking of VLP binding to its receptor and thereby uptake of VLPs by antigen-presenting cells. Our results suggest that repetitive vaccination with a cVLP for induction of cellular immune responses to an incorporated antigen may be of limited effectiveness due to the presence of neutralizing antibodies against the capsid proteins induced after the first application. This limitation could potentially be overcome by boosting with cVLPs containing the same target antigen incorporated into other papillomavirus-type VLPs.
Authors	D M Da Silva, D V Pastrana, J T Schiller, W M Kast
Journal	Virology (Virology) Vol. 290 Issue 2 Pg. 350-60 (Nov 25 2001) ISSN: 0042-6822 [Print] United States
PMID	11883199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antibodies, Viral Oncogene Proteins, Viral Papillomavirus E7 Proteins Papillomavirus Vaccines Viral Vaccines oncogene protein E7, Human papillomavirus type 16
Topics	Animals Antibodies, Viral (immunology) Female HeLa Cells Humans Immunization, Passive Mice Mice, Inbred C57BL Neutralization Tests Oncogene Proteins, Viral (immunology) Papillomaviridae (immunology) Papillomavirus E7 Proteins Papillomavirus Vaccines Recombination, Genetic Viral Vaccines (immunology) Virion (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!