Evaluation of Immunogenicity Levels in Women With HPV Vaccine in Mexico
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      In September 2009 the National Vaccination Council approved the policy for anti-HPV
      vaccination in 9-year-old girls with an extended scheme of 0, 6, and 60 months, under the
      following justification:

        -  Antibody induction due to the vaccine is greater than that produced by natural exposure
           to the virus

        -  Immune response in girls 9 to 11 years of age is similar to the response obtained after
           three doses in women 16 to 26 years of age

        -  The third dose will be administered at the time when maximum protection is required,
           near the onset of sexual activity Thus the National Institute of Public Health was
           commissioned to monitor anti-HPV antibody levels in women who received the anti-HPV
           vaccine to determine non-inferiority of the extended scheme in 9-year-old girls compared
           with the traditional scheme of 3 doses in women 18 to 24 years of age. To this end, a
           sentinel cohort will be formed to evaluate immunogenicity levels in 3 age groups, and
           stratified by vaccine type. The hypothesis is that in 9-year-old girls who are
           administered the amplified HPV vaccination scheme (0-6-60) show immunogenicity levels
           that are not lower than those of adult women who have been administered the traditional
           scheme (0-1/2-6).

      The main objectives are to monitor the levels of immunity induced by vaccination against HPV
      with two vaccination schemes with the quadrivalent vaccine: Traditional Extended (0-6-60
      months) and traditional (0-2-6); Monitoring levels of immunity induced by vaccination against
      HPV with three vaccine schemes with bivalent vaccine: Extended (0-6-60 months), traditional
      (0-1-6) and two doses (0- 6); as well as evaluating the interchangeability of the bivalent
      and quadrivalent vaccines in the third dose of extended scheme. The study design is to create
      a sentinel cohort of women vaccinated against HPV in the following comparison groups:

        -  Women of nine years with extended vaccination scheme with three doses of quadrivalent
           vaccine (0-6-60)

        -  Women of nine years with extended vaccination scheme with two doses of the quadrivalent
           vaccine and the third dose with bivalent (0-6-60)

        -  Women of nine years with traditional vaccination scheme with the quadrivalent HPV
           vaccine (0-2-6)

        -  Women between 18 and 24 years with traditional vaccination scheme with the quadrivalent
           HPV vaccine (0-2-6)

        -  Women of nine years with extended vaccination scheme with three doses of bivalent
           vaccine (0-6-60)

        -  Women of nine years with extended vaccination scheme with two doses of bivalent vaccine
           and the third tetravalent dose

        -  Women of nine years with two vaccine doses scheme with the bivalent HPV vaccine (0-6)

        -  Women of nine years with traditional vaccination scheme with bivalent HPV vaccine
           (0-1-6)

        -  Women between 18 and 24 years with traditional vaccination scheme with bivalent HPV
           vaccine (0-1-6)

        -  To monitoring HPV infections, at month 61 of follow-up, a group of 400 women aged 14-15
           years, who have not been vaccinated against HPV, will be invited , in order to make the
           monitoring of occurrence of HPV infections in urine per month 61, 72, 96 and 120 post
           dose 0 in vaccinated groups
    

Detailed description: 
      Hypothesis Girls 9 and 10 years of age who are administered the amplified anti/HPV
      vaccination scheme (0-6-60), show immunogenicity levels against HPV antibodies that are not
      lower than those of 9-year-old girls and adult women who have been administered the
      traditional scheme (0-1/2-6).

      The vaccination schemes for HPV traditional (0-1 / 2-6) and extended (0-6-60), are equivalent
      from the immunologically perspective and therefore the number of memory B and T lymphocytes
      as well as the structure of repertoire will be not different between schemes.

      Objectives The main objectives are to monitor the levels of immunity induced by vaccination
      against HPV with two vaccination schemes with the quadrivalent vaccine: Traditional Extended
      (0-6-60 months) and traditional (0-2-6); Monitoring levels of immunity induced by vaccination
      against HPV with three vaccine schemes with bivalent vaccine: Extended (0-6-60 months),
      traditional (0-1-6) and two doses (0- 6); as well as evaluating the interchangeability of the
      bivalent and quadrivalent vaccines in the third dose of extended scheme. The study design is
      to create a sentinel cohort of women vaccinated against HPV in the following comparison
      groups:

        -  Women of nine years with extended vaccination scheme with three doses of quadrivalent
           vaccine (0-6-60)

        -  Women of nine years with extended vaccination scheme with two doses of the quadrivalent
           vaccine and the third dose with bivalent (0-6-60)

        -  Women of nine years with traditional vaccination scheme with the quadrivalent HPV
           vaccine (0-2-6)

        -  Women between 18 and 24 years with traditional vaccination scheme with the quadrivalent
           HPV vaccine (0-2-6)

        -  Women of nine years with extended vaccination scheme with three doses of bivalent
           vaccine (0-6-60)

        -  Women of nine years with extended vaccination scheme with two doses of bivalent vaccine
           and the third tetravalent dose

        -  Women of nine years with two vaccine doses scheme with the bivalent HPV vaccine (0-6)

        -  Women of nine years with traditional vaccination scheme with bivalent HPV vaccine
           (0-1-6)

        -  Women between 18 and 24 years with traditional vaccination scheme with bivalent HPV
           vaccine (0-1-6)

        -  To monitoring HPV infections, at month 61 of follow-up, a group of 400 women aged 14-15
           years, who have not been vaccinated against HPV, will be invited , in order to make the
           monitoring of occurrence of HPV infections in urine per month 61, 72, 96 and 120 post
           dose 0 in vaccinated groups

      Methodology

      Study design:

      Creating a sentinel cohort of women vaccinated against HPV in three comparison groups:

        -  Women of nine years with extended vaccination scheme with three doses of quadrivalent
           vaccine (0-6-60)

        -  Women of nine years with extended vaccination scheme with two doses of the quadrivalent
           vaccine and the third dose with bivalent (0-6-60)

        -  Women of nine years with traditional vaccination scheme with the quadrivalent HPV
           vaccine (0-2-6)

        -  Women between 18 and 24 years with traditional vaccination scheme with the quadrivalent
           HPV vaccine (0-2-6)

        -  Women of nine years with extended vaccination scheme with three doses of bivalent
           vaccine (0-6-60)

        -  Women of nine years with extended vaccination scheme with two doses of bivalent vaccine
           and the third tetravalent dose

        -  Women of nine years with two vaccine doses scheme with the bivalent HPV vaccine (0-6)

        -  Women of nine years with traditional vaccination scheme with bivalent HPV vaccine
           (0-1-6)

        -  Women between 18 and 24 years with traditional vaccination scheme with bivalent HPV
           vaccine (0-1-6) Selecting the study population.

      A fraction of the population of females will be invited to participate in the study
      proportionately, combining strategies in schools and the community.

      A total of 2450 women will be recruited. For the study purposes, they will be classified by
      vaccine type administered, (tetravalent and bivalent), as well as by age group and
      vaccination scheme.

      Forming groups for evaluation.

      Two groups of participants will be formed. Participants will be classified by vaccine type
      received:

        1. Bivalent Vaccine. This group will consist of a total of 2000 women. Two thirds of them
           will be 9 to 10 years of age, and 500 will be 18 to 24 years of age. In the first age
           group, 1000 of them will be administered the vaccine in the amplified scheme of 0, 6, 60
           months. Five hundred females from this age group will be administered the vaccine
           according to the traditional scheme of 0, 1, 6 months. All females from the 18 to 24 age
           group will be administered the traditional scheme of 0, 1, 6 months.

        2. Tetravalent Vaccine:

      A total of 450 females will participate. The 9 to 10 year age group will include 300 women,
      and the 18 to 24 year age group will include 150 females.

      The vaccination scheme will be conformed as follows: In the group of 9- to 10-year-olds, 150
      of them will be administered the vaccine in the amplified scheme of 0, 6, 60 months, and the
      remaining 150 will receive the vaccine under the traditional scheme of 0, 2, 6 months. The
      group of 18- to 24-year-old women will be conducted under the traditional scheme of 0, 2 and
      6 months.

      The vaccination scheme will be assigned according to number in the record and/or geographical
      location.

      For quantification of immunological memory of B and T lymphocytes and characterizing
      lymphocytes B repertoire in women vaccinated against HPV, 60 participants for group,
      recruited for medical evaluation at month 60.

      To evaluate the interchangeability of quadrivalent and bivalent vaccines a randomization will
      be performed in the group of girls aged 14-15 years who have been assigned at the beginning
      of the project with extended vaccination scheme (0-6-60) with the bivalent vaccine, so that
      one third of this group will receive the bivalent vaccine, another third will receive the
      quadrivalent vaccine and the remaining third will no longer receive additional doses.
    

Intervention name(s): Bivalent Vaccines; Tetravalent Vaccine
Intervention type(s): Biological; Biological
Other intervention name(s): CERVARIX; Gardasil
Intervention MeSH terms: Vaccines
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Evaluation; Immunogenicity; Levels; Women; HPV; Vaccine; Mexico