Alternative Gardasil dosing schedules effective
Patients that were administered the three-dose quadrivalent human papillomavirus vaccine (Gardasil, Merck) with longer intervals between each dose had similar immune responses to those administered the vaccine on a standard dosing schedule, new data indicate.
“Clinicians can be reassured that if delays occur in administering the second and third doses of this vaccine, it still works very will in generating an immune response,” Kathleen M. Neuzil, MD, MPH, senior clinical advisor for vaccines at PATH, a global health nonprofit organization based in Seattle, said during a press briefing.
Current vaccine guidelines specify that the second and third doses in the quadrivalent HPV vaccine series be administered at two and six months after the first dose.
Despite strict adherence to these protocols during clinical trials, dosing schedules may vary in actual practice, raising concerns about the vaccine's efficacy in the general population, according to Neuzil.
Additionally, concerns remain about the feasibility of administering quadrivalent HPV vaccine according to the recommended schedule in developing countries, many of which lack adolescent vaccination programs and have a high burden of disease – accounting for approximately 88% of the 275,000 cervical cancer deaths that occur each year.
Neuzil and colleagues conducted a randomized noninferiority trial to determine whether three alternative dosing options could offer health care providers flexibility in administering the vaccine without sacrificing efficacy. Results were published in the April 12 issue of the Journal of the American Medical Association.
The researchers enrolled 903 girls aged 11 to 12 years who attended 6th and 7th grade at 21 schools in the Hoa Binh province of Vietnam and randomly assigned them to one of four vaccine schedules: the standard 0-, 2- and 6-month schedule; a 0-, 3- and 9-month schedule; a 0-, 6-, and 12-month schedule; and a 0-, 12- and 24-month schedule.
Antibody concentrations were analyzed from blood samples drawn before the first dose of vaccine was administered, before the third dose and one month after the third dose (n=807; 89.6%).
Geometric mean titers (GMCs) revealed participants that received all three doses in two of the alternative schedules — the 0-, 3- and 9-month schedule and the 0-, 6- and 12-month schedule — met noninferiority criteria, achieving robust antibody responses to HPV types 16 and 18, the two types responsible for causing 70% of cervical cancer.
However, participants in the 0-, 12- and 24-month group achieved noninferior GMCs only to HPV type 18, but not 16.
Despite this finding, antibody responses were still robust among all groups, Neuzil noted, adding that patients in this trial had higher overall levels of protective antibodies than older cohorts included earlier clinical trials.
“Although the yearly schedule did not meet noninferiority, antibody levels are still higher than those found in 16- to 23-year olds,” Neuzil said, adding that the exact concentration necessary to confer protection is not yet known.
Adverse events were minimal and mostly consisted of mild injection site reactions; no participants experienced syncope.