Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

Hannah H. Alphs, Ratish Gambhira, Balasubramanyam Karanam, Jeffrey N. Roberts, Subhashini Jagu, John T. Schiller, Weiguang Zeng, David C. Jackson, Richard S Roden

Research output: Contribution to journalArticle

Abstract

Persistent infection with the high-risk subset of genitotropic human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. Given the global burden of cervical cancer, a low-cost, broadly protective vaccine is needed. RG-1 is a cross-neutralizing and protective monoclonal antibody that recognizes residues 17-36 of HPV16 minor capsid protein L2. Because this epitope is highly conserved in divergent HPV types, we determined whether vaccination with HPV16 L2 17-36 peptide is broadly protective. The peptide was administered to BALB/c mice three times at monthly intervals, either alone or in the context of a synthetic lipopeptide vaccine candidate (P25-P2C-HPV) produced by linkage of the HPV peptide with a broadly recognized T helper epitope (P25) and the Toll-like receptor-2 (TLR2) ligand dipalmitoyl-S-glyceryl cysteine (P2C). In contrast to vaccination with the L2 17-36 peptide or P25-P2C alone, a potent L2-specific antibody response was generated to the P25-P2C-HPV lipopeptide when delivered either s.c. or intranasally. Sera from mice vaccinated with the P25-P2C-HPV lipopeptide neutralized not only HPV16 pseudovirions but also other evolutionarily divergent oncogenic genital (HPV18, HPV45) and cutaneous (HPV5, BPV1) types. The L2-specific antibody response depended on MHC class II, CD40, and MyD88 signaling. Additionally, vaccination with the P25-P2C-HPV lipopeptide protected mice from homologous challenge with HPV16 pseudovirions at cutaneous and genital sites and heterologous challenge with HPV45 pseudovirions. If provided in the appropriate context, therefore, HPV16 L2 17-36 might be used in a totally synthetic cross-protective HPV vaccine.

Original languageEnglish (US)
Pages (from-to)5850-5855
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number15
DOIs
StatePublished - Apr 15 2008

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Lipopeptides
Synthetic Vaccines
Epitopes
Peptides
Vaccination
Uterine Cervical Neoplasms
Antibody Formation
Toll-Like Receptor 2
Papillomavirus Vaccines
Skin
Capsid Proteins
Vaccines
Genotype
Monoclonal Antibodies
Ligands
Costs and Cost Analysis
Infection
Serum

ASJC Scopus subject areas

  • Genetics
  • General

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Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2. / Alphs, Hannah H.; Gambhira, Ratish; Karanam, Balasubramanyam; Roberts, Jeffrey N.; Jagu, Subhashini; Schiller, John T.; Zeng, Weiguang; Jackson, David C.; Roden, Richard S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 15, 15.04.2008, p. 5850-5855.

Research output: Contribution to journalArticle

Alphs, Hannah H. ; Gambhira, Ratish ; Karanam, Balasubramanyam ; Roberts, Jeffrey N. ; Jagu, Subhashini ; Schiller, John T. ; Zeng, Weiguang ; Jackson, David C. ; Roden, Richard S. / Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 15. pp. 5850-5855.
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