TY - JOUR
T1 - Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles
AU - Pinto, Ligia A.
AU - Edwards, Jessica
AU - Castle, Philip E.
AU - Harro, Clayton D.
AU - Lowy, Douglas R.
AU - Schiller, John T.
AU - Wallace, Dora
AU - Kopp, William
AU - Adelsberger, Joseph W.
AU - Baseler, Michael W.
AU - Berzofsky, Jay A.
AU - Hildesheim, Allan
N1 - Funding Information:
Received 26 September 2002; accepted 11 February 2003; electronically published 9 July 2003. Financial support: National Cancer Institute, National Institutes of Health (grant N01-CO-12400). Reprints or correspondence: Dr. Ligia A. Pinto, NCI-Frederick, Bldg. 469, Rm. 120, Frederick, MD 21702 (lpinto@ncifcrf.gov).
PY - 2003/7/15
Y1 - 2003/7/15
N2 - 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.
AB - 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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U2 - 10.1086/376505
DO - 10.1086/376505
M3 - Article
C2 - 12854090
AN - SCOPUS:0041314080
SN - 0022-1899
VL - 188
SP - 327
EP - 338
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -