This was not the case for HPV52, however, which demonstrated no increase in positivity between the middle and high tertiles. The number of non-vaccine types neutralized per serum increased with type-specific tertile such that the median number of non-vaccine types neutralized by sera in the lowest HPV16 tertile was 1.0 (IQR, 0.5–1.5) compared with 2.0 (2.0–2.5) and 3.0 (IQR, 1.5–4.0) for learn more the middle and high tertiles, respectively. Neutralizing antibody titers against non-vaccine types HPV31, 33, 35, 45, 52 and 58 increased in association with increasing vaccine-type tertiles (Table 2 and Fig. 1). For example, for HPV31, the median
(IQR) titer was 34 (10–71) for the low HPV16 tertile, rising to 78 (47–169) for the middle and 195 (92–490) for the high HPV16 tertile. Significant associations were found between cross-neutralizing titers for non-vaccine types and vaccine-type tertile for HPV31, 33, 35, 45, 52 and 58) when assessed by the Kruskal–Wallis test (data not shown) or the test for trend across ordered groups (Table 2 and Fig. 1). As expected, HPV18 neutralizing antibody titers were significantly associated with increasing HPV16 tertiles (trend analysis and Kruskal–Wallis test; p < 0.001). Cross-neutralization titers were overall very low, being <1% of the respective type-specific, HPV16 or HPV18 titer: for example, HPV31 (median 0.49% [IQR 0.24–1.02%]),
HPV33 (0.13% [0.09–0.24%]) and HPV45 (0.50% [0.18–1.02%]). In contrast to the increase across Selleckchem Epacadostat the vaccine-type tertiles of the percentage of individuals with, and levels of, cross-neutralizing titers (Table 2), the relative magnitude of non-vaccine to vaccine titers decreased across the tertiles. For example for HPV31, the median (IQR) percentage of type-specific titer was 0.69% (0.47–1.08%) for the low HPV16 tertile, falling to 0.49% (0.25–1.07%) for the middle and 0.29% (0.17–0.77%) for the high HPV16 tertile (trend analysis; p = 0.018). In this study we
have attempted to estimate the propensity for serum taken from 13 to 14 year old girls recently vaccinated before with the bivalent HPV vaccine to neutralize pseudoviruses representing genetically related, non-vaccine HPV types within the A9 and A7 species groups. Neutralizing antibodies against non-vaccine A9 HPV types were commonly detected within this study group, with antibodies against HPV31 and HPV33 being the most frequently detected and of the highest titer. The only A7 non-vaccine HPV type for which a significant neutralizing antibody response was found was HPV45. Neutralizing antibody titers against HPV31, 33, 35, 45 (and to a lesser extent HPV52 and 58) were significantly associated with their related vaccine-type antibody titers, suggesting that the generation of cross-neutralizing antibodies is at least coincident with the host immune response to vaccination.