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Journal of Virology, May 2001, p. 4752-4760, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4752-4760.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

S. Gerber,1 C. Lane,1 D. M. Brown,1 E. Lord,1 M. DiLorenzo,1 J. D. Clements,2 E. Rybicki,3 A.-L. Williamson,3 and R. C. Rose1,*

University of Rochester Medical Center, Rochester, New York1; Tulane University, New Orleans, Louisiana2; and University of Cape Town, Cape Town, Republic of South Africa3

Received 6 October 2000/Accepted 13 February 2001

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.

* Corresponding author. Mailing address: University of Rochester Medical Center, Department of Medicine, Box 689, 601 Elmwood Ave., Rochester, NY 14642. Phone: (716) 275-5871. Fax: (716) 442-9328. E-mail: Robert_Rose{at}urmc.rochester.edu.

Journal of Virology, May 2001, p. 4752-4760, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4752-4760.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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