Even a single dose of the human papillomavirus 16/18 virus-like particle vaccine appears to be immunogenic for at least 4 years, inducing an antibody response only slightly lower than that from two or the recommended three doses, according to a report in the November issue of Cancer Prevention Research.
Geometric mean titers (GMTs) of HPV antibodies persisted at a plateau level from 6 months after vaccination until the conclusion of this 4-year study, regardless of whether the female participants received one, two, or three doses of the vaccine. In all cases, the GMTs were higher than those induced from natural HPV infection, said Dr. Mahboobeh Safaeian of the division of cancer epidemiology and genetics, National Cancer Institute, Bethesda, Md., and her associates.
These findings that long-term protection may not require the fivefold higher antibody titers induced by three doses of the vaccine may have important implications for HPV virus-like particle (VLP) vaccine programs. Fewer doses would be less expensive and much easier to deliver, particularly in the developing world where more than 85% of cervical cancers occur and where they are the primary cause of cancer-related death in women, the investigators said.
Dr. Safaeian and her colleagues evaluated the immunogenicity of the HPV16/18 VLP vaccine by studying women who participated in the Costa Rica Vaccine Trial. In this publicly funded, community-based phase III study, 7,466 women were randomly assigned to receive either the HPV or the hepatitis A vaccine (control group). Approximately 20% of the study population received fewer than the recommended three doses of each vaccine.
For their study, Dr. Safaeian and her associates assessed serum samples from 78 women who received one HPV vaccine dose, 140 who received one dose at baseline and a second dose 1 month later, 52 who received one dose at baseline and a second dose 6 months later, and 120 who received all three doses. For comparison, they also assessed serum samples from 113 women who were seropositive for HPV 16 or 18 at baseline from naturally occurring infection.
Almost all of the study subjects in all the dose groups were seropositive for HPV antibodies at 1 month after the first dose, "indicating that all groups had similar intrinsic ability to respond to the vaccine," the investigators wrote (Cancer Prev. Res. 2013 November [doi:10.1158/1940-6207.CAPR-13-0203]).
Antibody GMTs were stable in all dose groups from 6 months post vaccination throughout the remainder of the 4-year follow-up. HPV antibody levels at 1 year were strongly predictive of what those levels would be at 3 and 4 years across all dose groups.
Among women who only received a single dose of the HPV16/18 vaccine, 54% had HPV16 antibody levels and 81% had HPV18 antibody levels comparable with those in women who received all three doses. "Our study is the first to show that even a single HPV16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated women at the end of 4-year follow-up, although the titers were lower than after 2 or 3 doses," Dr. Safaeian and her associates said.
"Coupled with our previous demonstration that a single vaccine dose of [HPV vaccine] induced strong protection in the Costa Rica Vaccine Trial, these findings suggest that antibody titers induced by two or three vaccine doses may be substantially higher than needed for long-term protection," they added.
HPV16 antibody levels were 24 times higher and HPV18 antibody levels were 14 times higher among women who received two doses of the vaccine than among women who had been infected naturally. HPV16 antibody levels were nine times higher and HPV18 antibody levels were five times higher among women who only received one dose of the vaccine than among those who had already been infected naturally.
This study was supported by the National Cancer Institute, the National Institutes of Health Office of Research on Women’s Health, and the Ministry of Health of Costa Rica. GlaxoSmithKline provided the vaccine and support for other aspects of the trial. Dr. Safaeian’s associates reported ties to GlaxoSmithKline, Merck, and DDl Diagnostic Laboratory.