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Journal of Virology, November 2007, p. 11585-11592, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01577-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Protection of Rabbits against Challenge with Rabbit Papillomaviruses by Immunization with the N Terminus of Human Papillomavirus Type 16 Minor Capsid Antigen L2{triangledown}

Ratish Gambhira,1 Subhashini Jagu,1 Balasubramanyam Karanam,1 Patti E. Gravitt,2 Timothy D. Culp,5 Neil D. Christensen,5 and Richard B. S. Roden1,3,4*

Departments of Pathology,1 Epidemiology,2 Oncology,3 Gynecology and Obstetrics, The Johns Hopkins University, Baltimore, Maryland,4 Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania5

Received 19 July 2007/ Accepted 9 August 2007

Current L1 virus-like particle (VLP) vaccines provide type-restricted protection against a small subset of the human papillomavirus (HPV) genotypes associated with cervical cancer, necessitating continued cytologic screening of vaccinees. Cervical cancer is most problematic in countries that lack the resources for screening or highly multivalent HPV VLP vaccines, suggesting the need for a low-cost, broadly protective vaccinogen. Here, N-terminal L2 polypeptides comprising residues 1 to 88 or 11 to 200 derived from HPV16, bovine papillomavirus type 1 (BPV1), or cottontail rabbit papillomavirus (CRPV) were produced in bacteria. Rabbits were immunized with these N-terminal L2 polypeptides and concurrently challenged with CRPV and rabbit oral papillomavirus (ROPV). Vaccination with either N-terminal L2 polypeptides of CRPV effectively protected rabbits from CRPV challenge but not from papillomas induced by cutaneous challenge with CRPV genomic DNA. Furthermore, papillomas induced by CRPV genomic DNA deficient for L2 expression grew at the same rate as those induced by wild-type CRPV genomic DNA, further suggesting that the L2 polypeptide vaccines lack therapeutic activity. Neutralizing serum antibody titers of >15 correlated with protection (P < 0.001), a finding consistent with neutralizing antibody-mediated protection. Surprisingly, a remarkable degree of protection against heterologous papillomavirus types was observed after vaccination with N-terminal L2 polypeptides. Notably, vaccination with HPV16 L2 11-200 protected against cutaneous and mucosal challenge with CRPV and ROPV, respectively, papillomaviruses that are evolutionarily divergent from HPV16. Further, vaccination with HPV16 L2 11-200 generates broadly cross-neutralizing serum antibody, suggesting the potential of L2 as a second-generation preventive HPV vaccine antigen.

* Corresponding author. Mailing address: Room 308, Cancer Research Building 2, Department of Pathology, Johns Hopkins School of Medicine, 1550 Orleans St., Baltimore, MD 21231. Phone: (410) 502-5161. Fax: (443) 287-4295. E-mail: roden{at}jhmi.edu

{triangledown} Published ahead of print on 22 August 2007.

Journal of Virology, November 2007, p. 11585-11592, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01577-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Day, P. M., Gambhira, R., Roden, R. B. S., Lowy, D. R., Schiller, J. T. (2008). Mechanisms of Human Papillomavirus Type 16 Neutralization by L2 Cross-Neutralizing and L1 Type-Specific Antibodies. J. Virol. 82: 4638-4646 [Abstract] [Full Text]  
  • Alphs, H. H., Gambhira, R., Karanam, B., Roberts, J. N., Jagu, S., Schiller, J. T., Zeng, W., Jackson, D. C., Roden, R. B. S. (2008). Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2. Proc. Natl. Acad. Sci. USA 105: 5850-5855 [Abstract] [Full Text]  


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