Human Papillomavirus Virus-Like Particles Are Efficient Oral Immunogens when Coadministered with Escherichia coli Heat-Labile Enterotoxin Mutant R192G or CpG DNA

Authors

S. Gerber, University of Rochester Medical Center
C. Lane, University of Rochester Medical Center
Deborah M. Brown, University of Rochester Medical CenterFollow
E. Lord, University of Rochester Medical Center
M. Dilorenzo, University of Rochester Medical Center
J. D. Clements, Tulane University, New Orleans, Louisiana
E. Rybicki, University of Cape Town, Cape Town, Republic of South Africa
A.-L. Williamson, University of Cape Town, Cape Town, Republic of South Africa
R. C. Rose, University of Rochester Medical Center

Document Type

Article

Date of this Version

May 2001

Comments

Published in JOURNAL OF VIROLOGY, 0022-538X/01/$04.0010 DOI: 10.1128/JVI.75.10.4752-4760.2001 May 2001, p. 4752-4760 Vol. 75, No. 10. Copyright © 2001, American Society for Microbiology. Used by permission.

Abstract

Certain human papillomaviruses (HPVs) cause most cervical cancer, which remains a significant source of morbidity and mortality among women worldwide. HPV recombinant virus-like particles (VLPs) are promising vaccine candidates for controlling anogenital HPV disease and are now being evaluated as a parenteral vaccine modality in human subjects. Vaccines formulated for injection generally are more costly, more difficult to administer, and less acceptable to recipients than are mucosally administered vaccines. Since oral delivery represents an attractive alternative to parenteral injection for large-scale human vaccination, the oral immunogenicity of HPV type 11 (HPV-11) VLPs in mice was previously investigated; it was found that a modest systemic neutralizing antibody response was induced (R. C. Rose, C. Lane, S. Wilson, J. A. Suzich, E. Rybicki, and A. L. Williamson, Vaccine 17:2129–2135, 1999). Here we examine whether VLPs of other genotypes may also be immunogenic when administered orally and whether mucosal adjuvants can be used to enhance VLP oral immunogenicity. We show that HPV-16 and HPV-18 VLPs are immunogenic when administered orally and that oral coadministration of these antigens with Escherichia coli heat-labile enterotoxin (LT) mutant R192G (LT R192G) or CpG DNA can significantly improve anti-VLP humoral responses in peripheral blood and in genital mucosal secretions. Our results also suggest that LT R192G may be superior to CpG DNA in this ability. These findings support the concept of oral immunization against anogenital HPV disease and suggest that clinical studies involving this approach may be warranted.