Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

Ligia A. Pinto, Jessica Edwards, Philip E. Castle, Clayton D. Harro, Douglas R. Lowy, John T. Schiller, Dora Wallace, William Kopp, Joseph W. Adelsberger, Michael W. Baseler, Jay A. Berzofsky, Allan Hildesheim

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)327-338
Number of pages12
JournalJournal of Infectious Diseases
Volume188
Issue number2
DOIs
StatePublished - Jul 15 2003
Externally publishedYes

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Human papillomavirus 16
Cellular Immunity
Virion
Healthy Volunteers
Papillomavirus Infections
Vaccines
Cytokines
Vaccination
T-Lymphocytes
Neutralizing Antibodies
Immunization
Placebos
Interleukin-5
Capsid Proteins
Uterine Cervical Neoplasms
Interleukin-10
Interferons
Blood Cells
Neoplasms
B-Lymphocytes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. / 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.

In: Journal of Infectious Diseases, Vol. 188, No. 2, 15.07.2003, p. 327-338.

Research output: Contribution to journalArticle

Pinto, LA, Edwards, J, Castle, PE, Harro, CD, Lowy, DR, Schiller, JT, Wallace, D, Kopp, W, Adelsberger, JW, Baseler, MW, Berzofsky, JA & Hildesheim, A 2003, 'Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles', Journal of Infectious Diseases, vol. 188, no. 2, pp. 327-338. https://doi.org/10.1086/376505
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. / Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. In: Journal of Infectious Diseases. 2003 ; Vol. 188, No. 2. pp. 327-338.
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abstract = "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.",
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