Antibody, cytokine and cytotoxic T lymphocyte responses in chimpanzees immunized with human papillomavirus virus-like particles

Vaccine. 2001 Jun 14;19(27):3733-43. doi: 10.1016/s0264-410x(01)00093-7.


We evaluated antibody, cytokine (IFN-gamma, IL-5, TNF-alpha), and cytotoxic T lymphocyte (CTL) responses in chimpanzees immunized with monovalent or quadrivalent (HPV-6, -11, -16, -18) L1 virus-like particle (VLP) vaccines administered i.m. on aluminum hydroxyphosphate (alum) at weeks 0, 8 and 24. Maximum serum antibody titers to type-specific, neutralizing, conformational epitopes on HPV-11 or -16 L1 VLPs were detected by radioimmunoassay (RIA) four weeks after the second and third immunizations. HPV-11 and -16 neutralizing antibodies were also detected at similar time points with an Human papillomaviruses (HPV) neutralization assay using pseudovirions. Depending on the VLP type used for immunization, HPV type-specific cytokine responses were most frequently seen four weeks after the second or third immunizations and between weeks 44-52. Transient HPV-16 L1-specific CTL activity was observed only between weeks 16-24 in 3 of 22 (13.6%) chimpanzees immunized with HPV-16 L1 VLPs. These findings provide evidence that immunization with multivalent L1 VLPs on alum can evoke both neutralizing antibodies and Th1 and Th2 cytokine responses to several HPV types; however, induction of CTLs is infrequent.

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis*
  • Cytokines / biosynthesis*
  • Cytotoxicity, Immunologic
  • Humans
  • Immunization Schedule
  • Lymphocyte Activation / immunology
  • Lymphocyte Subsets / immunology
  • Pan troglodytes
  • Papillomaviridae / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Virion / immunology*


  • Antibodies, Viral
  • Cytokines