Cellular Immune Responses to Human Papillomavirus (HPV)-16 L1 in Healthy Volunteers Immunized with Recombinant HPV-16 L1 Virus-Like Particles

• Published in: The Journal of infectious diseases Vol. 188; no. 2; pp. 327 - 338
• Main Authors: Pinto, Ligia A., Edwards, Jessica, Castle, Philip E., Harro, Clayton D., Lowy, Douglas R., Schiller, John T., Wallace, Dora, Kopp, William, Adelsberger, Joseph W., Baseler, Michael W., Berzofsky, Jay A., Hildesheim, Allan
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.07.2003; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens; Antigens, Viral - immunology; B-Lymphocytes - immunology; Biological and medical sciences; Cytokines; Cytokines - immunology; Double-Blind Method; Female; Fundamental and applied biological sciences. Psychology; Human papillomavirus 16; Humans; Immunization; Infections; Lymphocyte Activation; Male; Microbiology; Papillomaviridae - immunology; Placebos; Substrate Specificity; T lymphocytes; T-Lymphocytes - immunology; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Viral Vaccines - immunology; Virology; Viruses; Human; Immunization; Healthy subject; Virus like particle; Cellular immunity; Vaccine; Papovaviridae; Papillomavirus; Virus; Human papillomavirus 16; Human papillomavirus; Immunogenicity; Phase II trial; Humoral immunity
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/376505

The causal association between papillomavirus (HPV) infection and cervical cancer has been demonstrated; the development of a prophylactic vaccine to protect against HPV infection may therefore reduce the incidence of this cancer worldwide. Noninfectious HPV-like particles (VLPs), composed of the L1 major capsid protein, are current candidate vaccines for prevention of HPV infection and cervical neoplasia. Although neutralizing antibodies have a pivotal role in the prevention of initial infection, cellular immune responses to HPV antigens may have an important role in viral clearance. A phase II trial was conducted to further evaluate the immunogenicity of a recombinant HPV-16 L1 VLP vaccine administered intramuscularly, without adjuvant, at 0, 1, and 6 months. Cell-mediated immune responses (lymphoproliferation and cytokine production) to HPV-16 L1 VLPs were evaluated in peripheral blood mononuclear cells (PBMCs) from 43 individuals receiving the L1 VLP vaccine and from 10 individuals receiving placebo. Vaccination resulted, at months 2 and 7 (i.e., 1 month after the second immunization and 1 month after third immunization, respectively), in increases in T cell-proliferative response to HPV-16 L1 VLPs (P<.001). In addition, significant increases in cytokine (interferon-γ, interleukin [IL]-5 and IL-10) responses to L1 VLPs were observed after vaccination (P<.001). The strongest cytokine responses at month 7 were observed in individuals with high antibody titers at month 2, suggesting that neutralizing antibodies generated by initial vaccination may augment T cell responses to subsequent booster vaccinations. No significant increases in lymphoproliferative or cytokine responses to L1 VLPs were observed in individuals receiving placebo. In summary, the HPV-16 L1 vaccine induces not only robust B cell responses but also L1-specific T cell responses detectable by proliferation of both CD4+ and CD8+ T cells and in vitro production of both Th1-and Th2-type cytokines. Future efficacy studies are needed to evaluate whether and/or how VLP vaccines confer protection against genital HPV infection and associated disease.