Kathy Boltz, PhD
November 20, 2013
Women vaccinated with one dose of a human papillomavirus (HPV) vaccine had antibodies against the viruses that remained stable in their blood for 4 years, suggesting that a single dose of vaccine may be sufficient to generate long-term immune responses and protection against new HPV infections, and ultimately cervical cancer, according to a new study.
"The latest Morbidity and Mortality Weekly Report from the Centers for Disease Control and Prevention on vaccination coverage indicates that in 2012, only 53.8% of girls between 13 and 17 years old initiated HPV vaccination, and only 33.4% of them received all three doses," said lead author Mahboobeh Safaeian, PhD, an investigator in the Division of Cancer Epidemiology and Genetics at the National Cancer Institute (NCI) in Bethesda, Maryland.
"We wanted to evaluate whether two doses, or even one dose, of the HPV 16/18 L1 VLP vaccine [Cervarix] could induce a robust and sustainable response by the immune system," she added. "We found that both HPV 16 and HPV 18 antibody levels in women who received one dose remained stable 4 years after vaccination. Our findings challenge previous dogma that protein subunit vaccines require multiple doses to generate long-lived responses."
Data for this study are from the NCI-funded phase III clinical trial to test the efficacy of Cervarix in women from Costa Rica. The study was published in Cancer Prevention Research (2013; doi:10.1158/1940-6207.CAPR-13-0203).
About 20% of the women in the study received fewer than three doses of the vaccine, not by design. The researchers looked for the presence of an immune response to the vaccine (measured by antibody levels) in blood samples drawn from 78, 192, and 120 women who received one, two, and three doses of the vaccine, respectively, and compared the results with data from 113 women who did not receive vaccination but had antibodies against the viruses in their blood because they were infected with HPV in the past.
The researchers found that 100% of the women in all three groups had antibodies against HPV 16 and 18 in their blood for up to 4 years. Antibody levels were comparable for women receiving two doses 6 months apart and those receiving the full three doses.
The researchers also found that while antibody levels among women who received one dose were lower than among those who received the full three doses, the levels appeared stable, suggesting that these are lasting responses. In addition, the levels of antibodies in women from the one- and two-dose groups were 5 to 24 times higher than the levels of antibodies in women who did not receive vaccination, but had prior HPV infection.
“It is important to note that persistence of antibody responses after a single dose has not been evaluated for Gardasil, the quadrivalent HPV vaccine that is more widely used in the United States and many other countries," stated Safaeian.
Durable Antibody Responses Following One Dose of the Bivalent Human Papillomavirus L1 Virus-Like Particle Vaccine in the Costa Rica Vaccine Trial
Mahboobeh Safaeian1, Carolina Porras, Yuanji Pan, Aimee Kreimer, John T. Schiller, Paula Gonzalez, Douglas R. Lowy, Sholom Wacholder, Mark Schiffman1, Ana C. Rodriguez, Rolando Herrero, Troy Kemp, Gloriana Shelton, Wim Quint, Leen-Jan van Doorn, Allan Hildesheim, Ligia A. Pinto, for the CVT Group
Abstract: The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection.
Cancer Prev Res 2013, 6(11):1242–50. doi:10.1158/1940-6207.CAPR-13-0203