One dose of HPV vaccine may be enough

One dose of HPV vaccine may be enough

4/11/2013

A single dose of human papillomavirus vaccine (HPV) achieved stable antibody levels at 48 months, suggesting that one dose of vaccine might afford adequate protection, according to a study from Central America.

Patients who received one dose of vaccine had geometric mean titers (GMTs) that were 5 (HPV 18) to 9 times (HPV 16) higher than those of non-immunized, seropositive women. Women who received two of the three scheduled doses had GMTs 14 to 24 times higher than those of the nonimmunized group.

One or two doses of vaccine produced lower GMTs as compared with three doses, but the magnitude and durability of the antibody responses warrant further study, Mahboobeh Safaeian, PhD, of the National Cancer Institute, and colleagues reported online in Cancer Prevention Research.

"Our study is the first to show that even a single HPV 16/18 vaccine dose induces an antibody response that was readily detected in all vaccinated young women at the end of the 4-year follow-up, although the titers were lower than after two or three doses and the number of one- and two-dose recipients was limited," the authors said.

"Critically, the GMTs remained at a stable plateau level from 6 months postvaccination until study end that was higher than the GMTs induced from natural infection."

The durability of response resembled that of an attenuated live-virus vaccine rather than a protein immunogen and has not been reported previously for noninfectious vaccines, the authors added. The findings have implications for future development of virus-like particle (VLP) vaccines.

The findings follow a previous report from the same group, documenting the unexpected efficacy of one or two doses of bivalent HPV vaccine for preventing persistent HPV 16 and 18 infection among women in Costa Rica. The observations have particular relevance for developing nations with limited resources. However, even in developed nations, many patients fail to complete the immunization protocol, which calls for three vaccine doses.

From a research perspective, investigators remained uncertain as to whether the durable efficacy was associated with stable antibody titers or occurred despite waning titers typical of VLP vaccines, which require booster doses to maintain efficacy.

To investigate the relationship between antibody titers and vaccine efficacy, Safaelan and colleagues measured HPV 16- and 18-specific antibody levels in four patient groups: 78 patients who received one vaccine dose, 140 patients who received two doses separated by 1 month, 52 patients who received two doses separated by 6 months, and 120 patients who received all three doses of the vaccine.

Investigators also measured antibody titers in 113 unvaccinated women who were HPV 16- and 18-seropositive, presumably from natural infection.

The patients were participants in the Costa Rica Vaccine Trial involving 7,466 women randomized to receive the HPV vaccine or a hepatitis A vaccine.

Each participant's seropositivity was confirmed by ELISA analysis of serum samples, and HPV DNA was quantified by polymerase chain reaction amplification.

Almost all vaccinated patients tested seropositive within 1 month of the first dose of vaccine. GMTs did not differ significantly among the vaccinated groups, indicating that participants in each group had comparability intrinsic ability to respond to the vaccine.

Antibody titers for HPV 16 remained stable from 36 to 48 months in the one- and two-dose groups and remained stable for HPV 18 across all groups.

GMTs in the one-dose group remained stable at about 130 EU/mL for HPV 16 and 70 EU/mL for HPV 18 from months 6 through 48. Among women who were seronegative at enrollment, GMTs in the one-dose group were about 100 for HPV 16 and 60 for HPV 18 from 6 through 48 months.

After 4 years of follow-up, the ratios of HPV 16 and HPV 18 GMTs for the one-dose group versus the three-dose group were 0.18 (95% CI 0.14-0.24) and 0.21 (95% CI 0.16-0.28). Even so, GMTs in the one-dose group were nine times higher for HPV 16 and five times higher for HPV 18 as compared with the natural-infection group.

"Our study clearly establishes that activation of memory B cells by a booster dose is not required for induction of persistent antibody responses by a protein-subunit vaccine," the authors concluded. "It seems unlikely that exposure to HPV virions contributed substantially to the longevity of the VLP antibody response in most vaccinees."

Authorities in oncology, infectious disease, and women's health all agreed that the findings, though preliminary, have potentially far-reaching implications.

Robert Morgan, MD, of City of Hope in Duarte, Calif., said eliminating vaccine boosters would substantially decrease the cost of immunization and substantially improve compliance. He emphasized that the ideal vaccination schedule remains to be determined, as investigational multivalent vaccine are currently in clinical trials.

The findings build on previously reported evidence and could have major public health implications, said Sarah Temkin, MD, of the University of Maryland in Baltimore.

"Adherence to all three injections of the vaccine is low," Temkin told MedPage Today by email. "In Baltimore, for example, completion rates range from 20% to 38.3%. From a public health perspective, it is reassuring that the women who are not completing all three recommended injections may still be well protected against HPV-related diseases."

The results also have implications for the multivalent vaccine, according to Chris Harrison, MD, of Children's Mercy Hospital and Clinics in Kansas City. Studies have shown that cross-protection against other HPV strains requires high antibody titers when only HPV 16 and 18 are targeted by a vaccine.

"The titers in this study are low at 4 years after one dose," Harrison said. "It indicates that multivalence is probably still necessary. It actually would give us more comfort -- if we get to the point where only one dose is necessary -- to have those other cancer-producing types in the vaccine, not just 16 and 18."

 

Source: MedPage Today: http://www.medpagetoday.com/PrimaryCare/Vaccines/42688