HPV vaccine may lose efficacy during ovulation

Specific anti-human papillomavirus (HPV) 16 antibodies induced by vaccination with HPV16 virus-like particles (VLP) decline during ovulation to levels that may impair protection against the virus, according to a report in the August 6th Journal of the National Cancer Institute.

“The level of specific antibodies in the human female genital tract is likely to be an important determinant of vaccine efficacy,” the authors explain, but “previous studies have not determined whether HPV immunization results in specific antibodies in the human female genital tract or whether such levels vary during contraceptive or ovulatory cycles.”Dr. Douglas R. Lowy from National Cancer Institute in Bethesda, Maryland and associates monitored vaccine-specific and total immunoglobulin levels in the genital tract of healthy adult women immunized with a candidate HPV vaccine during different phases of ovulatory and contraceptive cycles.Serum levels of specific anti-HPV16 IgG were similar in the ovulatory and contraceptive groups, the authors report, and all participants developed anti-HPV16 antibodies in their cervical secretions.In the ovulatory group, cervical anti-HPV16 IgG titers were highest during the proliferative phase of the menstrual cycle, the results indicate, falling an average of ninefold around the time of ovulation and then rebounding approximately threefold during the luteal phase. Cervical antibody titers did not correlate with serum antibody titers.In contrast, cervical anti-HPV16 IgG titers remained relatively constant throughout the menstrual cycle among women in the contraceptive group, the researchers note, and cervical antibody titers correlated closely with serum antibody titers (r = 0.86).Total IgG concentrations paralleled vaccine-specific IgG concentrations during ovulatory cycles, the report indicates, whereas total IgA levels did not vary significantly.Modest changes in the volume of cervical secretions during the menstrual cycle could not account for the decrease in antibody concentrations seen during the peri-ovulatory phase, the investigators report.”There are reasonable levels of HPV16 antibodies at the cervix of HPV16 VLP vaccinees, which goes along with the encouraging proof of principle efficacy results of the published Merck sponsored studies and the orally presented GlaxoSmithKline sponsored studies,” Dr. Lowy told Reuters Health.”However,” Dr. Lowy said, “for ovulating women, there is considerable menstrual cycle- dependent fluctuation in the antibody level at the cervix in ovulating women, in contrast to women on oral contraceptives, who maintain relatively constant levels. Therefore, it will be useful, in the phase III HPV vaccine efficacy trials, to determine whether there might be a difference in the degree of protection seen in ovulating women versus women using oral contraceptives.” “It is not clear whether protection against HPV infection is mediated mainly by transudated IgG or whether the antibody levels at the site of infection may actually be higher because infection may be associated with micro-trauma,” Dr. Lowy explained. “If the latter is true, the menstrual cycle-dependent changes in antibody levels may not have much effect on efficacy. If the former is true, the changes are more likely to affect efficacy.”Dr. Lowy added, that it is probable that “any vaccine whose efficacy depends on transudation of IgG may be similarly affected. The less the efficacy a hypothetical vaccine depends on transudated IgG, the less the fluctuation would be expected to influence efficacy.”(Source: J Natl Cancer Inst 2003;95:1128-1137: Reuters Health: Will Boggs, MD: August 5, 2003: Oncolink)