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Immunogenicity: Assays to Measure Immune Response: Because of the very high
efficacy of GARDASIL in clinical trials, it has not been possible to establish minimum anti-HPV 6,
anti-HPV 11, anti-HPV 16, and anti-HPV 18 antibody levels that protect against clinical HPV disease.
The immunogenicity of GARDASIL was assessed in 8,915 women (GARDASIL N = 4,666; placebo N = 4,249)18 to
26 years of age and 3,400 male (GARDASIL N = 1,071; placebo N = 275) and female (GARDASIL N = 1,471; placebo N = 583)
adolescents 9 to 17 years of age.
Type-specific assays with type-specific standards were used to assess immunogenicity to
each vaccine HPV type. These assays measured antibodies against neutralizing epitopes for each HPV type,
rather than the total antibodies directed at the VLPs in the vaccine. The scales for these assays are
unique to each HPV type; thus, comparisons across types and to other assays are not meaningful.
The assays used to measure the immune responses to GARDASIL were demonstrated to correlate with the capacity to neutralize live HPV virions.
Immune Response to GARDASIL: The primary immunogenicity analyses were conducted in
a per-protocol immunogenicity (PPI) population. This population consisted of individuals who were
seronegative and Polymerase Chain Reaction (PCR) negative to the relevant HPV type(s) at enrollment,
remained HPV PCR negative to the relevant HPV type(s) through 1 month Postdose 3 (Month 7), received all 3 vaccinations,
and did not deviate from the study protocol in ways that could interfere with the effects of the vaccine.
Overall, 99.9%, 99.8%, 99.8%, and 99.6% of individuals who received GARDASIL became anti-HPV 6,
anti-HPV 11, anti-HPV 16, and anti-HPV 18 seropositive, respectively, by 1 month Postdose 3 across
all age groups tested. GARDASIL induced high anti-HPV Geometric Mean Titers (GMTs) 1 month Postdose 3 in all age groups tested.
Anti-HPV levels induced by the vaccine were substantially higher than those measured in women
with evidence of having had an infection who then mounted an immune response that led to clearance of infection prior to enrollment.
In a study that measured immune responses to a 3-dose regimen of GARDASIL during the
course of the vaccination regimen, Postdose 2 antiHPV levels were higher than those observed
during long-term follow-up of the Phase III studies. Overall, 97.6 to 100% became anti-HPV 6,
anti-HPV 11, anti-HPV 16, and anti-HPV 18 seropositive, respectively, by 1 month Postdose 2.
These results support the observation that the protective efficacy of GARDASIL begins during the course of the 3-dose vaccination regimen.
Bridging the Efficacy of GARDASIL from Young Adults to Young Adolescents:
A clinical study compared anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18 responses
in 10- to 15-year-old boys and girls with responses in 16to 23-year-old adolescent and young adult women.
Among subjects who received GARDASIL, 99.1 to 100% became anti-HPV 6, anti- HPV 11, anti-HPV 16,
and anti-HPV 18 seropositive, respectively, by 1 month Postdose 3. Anti-HPV responses in both 10-
to 15-year-old girls and 10- to 15-year-old boys were significantly superior to those observed in 16- to 23-year-olds.
Similar outcomes were observed in a comparison of the anti-HPV responses 1 month Postdose 3
among 9- to 15-year-old girls with anti-HPV responses in 16- to 26-year-old adolescent and young adult
women in the combined database of immunogenicity studies for GARDASIL.
On the basis of this immunogenicity bridging, the efficacy of GARDASIL in 9to 15-year-old girls
is comparable to the efficacy of GARDASIL observed in the Phase III studies in 16- to 26-year-old adolescent and young adult women.
Evidence for Anamnestic (Immune Memory) Responses: GARDASIL boosts immunologically primed individuals.
For each HPV type, anti-HPV GMTs measured 1 month Postdose 3 were approximately 1.4- to 2.4-fold higher
in individuals with detectable antibodies and no evidence of infection for that type at Day 1 compared
with subjects who were seronegative and PCR negative for that type at Day 1.
There was no interference in the immune responses to vaccine HPV types induced by GARDASIL.
Seropositivity at Day 1 for one vaccine HPV type did not have a negative impact on Postdose 3 anti-HPV responses to other vaccine HPV types.
Persistence: In a study that evaluated the HPV 16 component of GARDASIL in 16- to
23-year-old women, anti-HPV 16 GMTs were robust at Month 7. GMTs declined through Month 24 and then
stabilized (see Figure 1). In a study that evaluated GARDASIL in 16- to 23-year old women, antiHPV 6,
anti-HPV 11, anti-HPV 16 and anti-HPV 18 GMTs were robust at Month 7. GMTs declined through Month 24
and then stabilized (eg, antiHPV 18 response - see Figure 2).
Schedule Flexibility: All subjects evaluated in the PPE populations of the Phase II
and III studies received the 3-dose regimen of GARDASIL within a 1-year period, regardless of the
interval between doses. An analysis of immune response data suggests that flexibility of ±1 month
for Dose 2 (ie, Month 1 to Month 3 in the vaccination regimen) and flexibility of ±2 months for
Dose 3 (ie, Month 4 to Month 8 in the vaccination regimen) do not substantially impact the
immune responses to GARDASIL (see DOSAGE AND ADMINISTRATION).
Studies with Other Vaccines: The safety and immunogenicity of co-administration
of GARDASIL with hepatitis B vaccine (recombinant) (same visit, injections at separate sites)
were evaluated in a randomized study of 1,871 women aged 16 to 24 years at enrollment.
Immune response and safety profile to both hepatitis B vaccine (recombinant) and GARDASIL
were similar whether they were administered at the same visit or at a different visit.
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