Kruskal–Wallis equality-of-populations rank test and the test for trend across ordered groups (trend analysis) were used to assess the difference between non-vaccine type neutralization data ordered BMS-754807 datasheet into tertiles based upon neutralizing antibody titers against the vaccine type. All tests were performed using the statistical package, Stata 10.1 (StataCorp, College Station, TX). Sixty-nine serum samples
were collected a median 5.9 (IQR 5.7–6.0) months after receiving a third dose of the Cervarix® vaccine. As expected, all (n = 69, 100%) individuals generated high titer neutralizing antibodies against HPV16 and HPV18 following vaccination ( Table 1), with HPV16 titers a median 3.5 (IQR, 1.7–5.8) fold higher than the corresponding HPV18 titers (Wilcoxon paired signed rank test; p < 0.001). Sera capable of neutralizing non-vaccine A9 HPV types were commonly found among this group of vaccinees (ranging from 15% to 87% of individuals, depending on the HPV type) with neutralization detected most frequently for HPV31, followed by (in order) 33, 52, 35, and 58. Sera capable of neutralizing non-vaccine HPV types within the A7 species group were fewer and almost completely restricted to reactivity
against HPV45. No inhibition of the control BPV pseudovirus was seen using these vaccine sera. Little or no non-specific inhibition of pseudovirus entry was seen using the HPV-naïve sera resulting see more in an apparent assay specificity of 99–100% (Table 1). The exception was pseudovirus HPV52 which was inhibited by four
sera, albeit to low titer, resulting in an apparent specificity of 95% (95% CI, 90–100) for this HPV type. No inhibition of the control BPV pseudovirus was seen using these HPV-naïve sera. Significant associations were found between the neutralizing antibody titers observed against HPV31, 33, 35, 45, 52 and 58 and the titers observed against their related vaccine-type Calpain (Spearman’s and Kendall’s rank correlation, p < 0.005; data not shown). However, using the more stringent Pearson’s product-moment correlation coefficient only HPV31 (r = 0.855; p < 0.001), HPV33 (r = 0.523; p < 0.001), HPV35 (r = 0.269; p = 0.026) and HPV45 (r = 0.485; p < 0.001) gave significant associations with their respective type-specific titers. As expected [12], a significant correlation was found between the neutralizing antibody titers for HPV16 and HPV18 (Spearman’s rho = 0.673; p < 0.001; Pearson’s r = 0.657; p < 0.001). The relationship between vaccine-type and non-vaccine type neutralization was further investigated by subdivision of the sera into tertiles based on the vaccine-type titers for each species group (HPV16 tertiles for A9 types and HPV18 tertiles for A7 types). For HPV types 31, 33, 35, 45 and 58 the percentage of individuals with a positive, non-vaccine type neutralization titer increased with each tertile of vaccine-type titer (Table 2).
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