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

We evaluated antibody, cytokine (IFN-gamma, IL-5, TNF-alpha), and cytotoxic T lymphocyte (CTL) responses in chimpanzees immunized with monovalent or q uadrivalent (HPV-6, -11, -16, -18) LI virus-like particle (VLP) Vaccines ad ministered i.m. on aluminum hydroxyphosphate (alum) at weeks 0, 8 and 24. M aximum 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 neutral izing antibodies were also detected at similar time points with an Human pa pillomaviruses (HPV) neutralization assay using pseudovirions. Depending on the VLP type used for immunization, HPV type-specific cytokine responses w ere most frequently seen four weeks after the second or third immunizations and between weeks 44-52. Transient HPV-16 L1-specific CTL activity was obs erved only between weeks 16-24 in 3 of 22 (13.6%) chimpanzees immunized wit h HPV-16 L1 VLPs. These findings provide evidence that immunization with mu ltivalent L1 VLPs on alum can evoke both neutralizing antibodies and Th1 an d Th2 cytokine responses to several HPV types; however, induction of CTLs i s infrequent. (C) 2001 Elsevier Science Ltd. All rights reserved.