Affiliations of authors: Laboratory of Cellular Oncology, Center for Cancer Research (DRL, JTS), Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics (AH), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Gynecology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (DNH).
Correspondence to: Douglas R. Lowy, MD, Laboratory of Cellular Oncology, Bldg. 37, Rm. 4106, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (e-mail: drl{at}helix.nih.gov)
We thank Drs. Barr and Koutsky for their comments related to our recently published article, in which we reported that human papillomavirus 16 (HPV16) antibody levels at the cervix, following systemic immunization with an HPV16 virus-like particle (VLP) vaccine, vary substantially during the course of the menstrual cycle (1). We agree that long-term studies of vaccinees are needed to determine whether, and to what degree, these variations in HPV16 antibody levels may influence vaccine efficacy several years after vaccination. As noted by Drs. Barr and Koutsky and by ourselves (2), such efficacy results should help to clarify whether serum antibody or cervical antibody levels are the primary correlate of vaccine efficacy. In ongoing long-term efficacy studies, it may be useful to distinguish between the group of women who, after the vaccination period, do not use hormonal contraceptives at all and the group of women who use hormonal contraceptives intermittently, because it may be difficult to infer, with the latter group of women, whether their risk of HPV exposure will be similar during intervals on and off hormonal contraceptives.
In addition, we would also like to point out that the magnitude of the fluctuation we observed in HPV16 antibody levels at the cervix during the menstrual cycle was also seen for total immunoglobulin G levels at the cervix (1). Therefore, we believe that the observed menstrual cycledependent changes in HPV16 antibody levels at the cervix have nothing to do with our HPV16 VLP vaccine having been formulated without adjuvant, and we would expect that analogous fluctuations in antibody levels would be seen following systemic immunization with any VLP-based vaccine. We also note that, in apparent contrast to the observations of Drs. Barr and Koutsky, we did not find increased immunogenicity from the addition of aluminum adjuvant to the 50-µg dose of VLPs used in our study (1), although we have observed an adjuvant effect from aluminum when given with a 10-µg dose of VLPs (3).
REFERENCES
1 Nardelli-Haefliger D, Wirthner D, Schiller JT, Lowy DR, Hildesheim A, Ponci F, et al. Specific antibody levels at the cervix during the menstrual cycle of women vaccinated with human papillomavirus 16 virus-like particles. J Natl Cancer Inst 2003;95:112837.
2 Lowy DR, Schiller JT. Papillomaviruses: prophylactic vaccine prospects. Biochim Biophys Acta 1999;1423:M18.[ISI][Medline]
3 Harro CD, Pang YY, Roden RB, Hildesheim A, Wang Z, Reynolds MJ, et al. Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like particle vaccine. J Natl Cancer Inst 2001;93: 28492.
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