HPV16 infection decreases vaccine-induced HPV16 antibody avidity: the CVT trial

Abstract

The HPV vaccine has shown sustained efficacy and consistent stabilization of antibody levels, even after a single dose. We defined the HPV16-VLP antibody avidity patterns over 11 years among women who received one- or three doses of the bivalent HPV vaccine in the Costa Rica HPV Vaccine Trial. Absolute HPV16 avidity was lower in women who received one compared to three doses, although the patterns were similar (increased in years 2 and 3 and remained stable over the remaining 8 years). HPV16 avidity among women who were HPV16-seropositive women at HPV vaccination, a marker of natural immune response to HPV16 infection, was significantly lower than those of HPV16-seronegative women, a difference that was more pronounced among one-dose recipients. No differences in HPV16 avidity were observed by HPV18 serostatus at vaccination, confirming the specificity of the findings. Importantly, point estimates for vaccine efficacy against incident, six-month persistent HPV16 infections was similar between women who were HPV16 seronegative and seropositive at the time of initial HPV vaccination for both one-dose and three-dose participants. It is therefore likely that this lower avidity level is still sufficient to enable antibody-mediated protection. It is encouraging for long-term HPV-vaccine protection that HPV16 antibody avidity was maintained for over a decade, even after a single dose.

Fig. 1. Antibody avidity over time among participants who were HPV16 seronegative at first HPV vaccination.

Dots represent the geometric mean antibody avidity index for the one-dose group (solid line) and the three-dose group (dashed line), and the error bars represent 95% confidence intervals (CI). Regression lines are estimated by regressing log(avidity) on either an intercept, an indicator for the second study visit, and/or study year, and reporting on the parameter the parameter 100(eβ-1).

Fig. 2. HPV16 antibody avidity over time, stratified by number of HPV vaccine doses received and HPV16 serostatus at time of initial HPV vaccination.

HPV16-seronegative status at first HPV vaccination is represented by the solid line and HPV16 seropositive at first HPV vaccination is represented by the dashed line. Dots represent the geometric mean antibody avidity index for the one-dose group (a) and the three-dose group (b) and the error bars represent 95% confidence intervals (CI). Regression lines are estimated by regressing log(avidity) on either an intercept, an indicator for the second study visit, and/or study year, and reporting on the parameter the parameter 100(eβ-1).

Fig. 3. HPV16 antibody avidity over time among HPV16 seronegative at initial HPV vaccination, stratified by number of HPV vaccine doses received and HPV18 serostatus at time of initial HPV vaccination.

The solid lines indicate the three-dose group, stratified by HPV18 seronegative (empty circles) and HPV18 seropositive (squares) at first HPV vaccination. The dashed lines indicate the one-dose group, stratified by HPV18 seronegative (empty circles) and HPV18 seropositive (squares) at first HPV vaccination. Error bars represent 95% confidence intervals (CI). Regression lines are estimated by regressing log(avidity) on either an intercept, an indicator for the second study visit, and/or study year, and reporting on the parameter the parameter 100(eβ-1).