ACIP Evaluates 2-Dose Bivalent, Quadrivalent, and 9-Valent HPV Vaccines

Doctor administering vaccine
Doctor administering vaccine
The ACIP discussed latest data from bivalent, quadrivalent, and 9-valent HPV vaccine trials.

Experts from the Advisory Committee on Immunization Practices (ACIP) discussed data from trials investigating 2-dose schedules for bivalent, quadrivalent, and 9-valent human papillomavirus (HPV) vaccines and the possibility of recommending 2 doses of HPV vaccine in the United States at their February 2016 meeting.

The World Health Organization (WHO) recommended a 2-dose HPV schedule for girls aged 9 to 14 years in October 2014, but there is no current licensure of a 2-dose schedule in the United States.

Alain Luxembourg, MD, PhD, director of clinical research at Merck, presented new findings from a 9-valent vaccine trial. The trial analyzed immunogenicity in both genders and compared the antibody response after 2 doses of vaccine with the 3 doses.

While the 9-valent vaccine was developed as a 3-dose vaccine, the 9-valent 2-dose study tested “noninferiority of GMTs (geometric mean titers) at 1 month after the last dose in girls and boys who received a 2-dose regimen vs young women who received a 3-dose regimen.”

The results of the trial showed that a 2-dose series of 9-valent vaccine in girls and boys aged 9 to 14, with the second dose administered 6 or 12 months following the first dose, generated noninferior anti-HPV antibody responses when compared with the 3-dose regimen in young women aged 16 to 26.

Researchers also observed lower HPV GMTs for some HPV types in girls who received 2 doses compared with girls the same age who received 3 doses.

Dr Luxembourg noted that additional research should be conducted to determine the durability of responses and long-term effectiveness in “long-term follow-up clinical studies and post-licensure epidemiological studies.”

Lauri Markowitz, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), presented data from trials examining bivalent and quadrivalent HPV vaccines. The main analyses used by regulatory agencies were comparisons of antibody response after a 2-dose HPV vaccine schedule in children aged 9 to 14 against 3 doses in young adult women.

In the trials, researchers found that the antibody response to a 2-dose schedule, administered at 0 and 6 months or at 0 and 12 months, in children aged 9 to 14 was noninferior to 3 doses in young adult women.

Dr Markowitz also noted that antibody titers were lower after 2 doses at 0 and 6 months compared with 3 doses in the same age group in some trials.

Elissa Meites, MD, MPH, also from the CDC’s NCIRD, noted that the ACIP will consider additional data at future meetings, including GRADE for 2-dose schedules, post-licensure effectiveness data, modeling data and cost-effectiveness, programmatic considerations, and additional follow-up data from 9-valent trials. No policy changes were recommended at this meeting.


Kempe A, Markowitz L, Luxembourg A, Meites E. Human Papillomavirus (HPV) Virus. Presented at the Advisory Committee on Immunization Practices; February 24, 2016; Atlanta, GA.