Seroepidemiology of human papillomavirus 16 (HPV16) L2 and generation of L2-specific human chimeric monoclonal antibodies

Joshua W. Wang, Subhashini Jagu, Wai Hong Wu, Raphael P. Viscidi, Anne Macgregor-Das, Jessica M. Fogel, Kihyuck Kwak, Sai Daayana, Henry Kitchener, Peter L. Stern, Patti E. Gravitt, Cornelia L. Trimble, Richard B.S. Roden

Research output: Contribution to journalArticle

Abstract

Presently, the seroprevalence of human papillomavirus (HPV) minor capsid antigen L2-reactive antibody is not well understood, and no serologic standard exists for L2-specific neutralizing antibodies. Therefore, we screened a total of 1,078 serum samples for HPV16 L2 reactivity, and these were obtained from four prior clinical studies: a population-based (n+880) surveillance study with a high-risk HPV DNA prevalence of 10.8%, a cohort study of women (n+160) with high-grade cervical intraepithelial neoplasia (CIN), and two phase II trials in women with high-grade vulvar intraepithelial neoplasia (VIN) receiving imiquimod therapy combined with either photodynamic therapy (PDT) (n+19) or vaccination with a fusion protein comprising HPV16 L2, E7, and E6 (TA-CIN) (n+19). Sera were screened sequentially by HPV16 L2 enzyme-linked immunosorbent assay (ELISA) and then Western blot. Seven of the 1,078 serum samples tested had L2-specific antibodies, but none were detectably neutralizing for HPV16. To develop a standard, we substituted human IgG1 sequences into conserved regions of two rodent monoclonal antibodies (MAbs) specific for neutralizing epitopes at HPV16 L2 residues 17 to 36 and 58 to 64, creating JWW-1 and JWW-2, respectively. These chimeric MAbs retained neutralizing activity and together reacted with 33/34 clinically relevant HPV types tested. In conclusion, our inability to identify an HPV16 L2-specific neutralizing antibody response even in the sera of patients with active genital HPV disease suggests the subdominance of L2 protective epitopes and the value of the chimeric MAbs JWW-1 and JWW-2 as standards for immunoassays to measure L2-specific human antibodies.

Original languageEnglish (US)
Pages (from-to)806-816
Number of pages11
JournalClinical and Vaccine Immunology
Volume22
Issue number7
DOIs
StatePublished - Jul 1 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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