4 years for the bivalent vaccine with 100% seropositivity maintained and at least 5 years for the quadrivalent vaccine with 98.8% seropositivity Galunisertib manufacturer maintained

[24]. The bivalent vaccine induces sustained antibody titres for HPV18 several fold higher than after natural infection, 8.4 years after initial vaccination with 100% seropositivity maintained. However, for the quadrivalent vaccine, 18 months after first vaccination, the induced antibody titres for HPV18 return to the level of natural infection, with a reduction in seropositivity over time [42]. A correlate for protection has not yet been established and further studies will determine whether these decreasing antibody levels are linked to reduced effectiveness. The immunogenicity of the bivalent and quadrivalent vaccine was Rapamycin cell line compared in a head-to-head trial. Neutralising antibodies (nAbs) against HPV16 and HPV18 were 3.7 and 7.3-fold higher, respectively for the bivalent vaccine compared to the quadrivalent vaccine in women of age 18–26 years old at month 7 after receiving the first dose [43]. These differences remained similar in older age groups. After 24 months of follow-up, the GMTs of nAbs were 2.4–5.8-fold higher for HPV16 and 7.7–9.4-fold higher for HPV-18 with the bivalent versus the quadrivalent vaccine [24] and [44]. This observation remained similar up to 48 months of follow-up: GMTs of nAbs were consistently

higher in those receiving the bivalent vaccine across all age strata: 2.0–5.2-fold higher for HPV16 and 8.6–12.8-fold higher for HPV18 [45]. The use of different adjuvants in the vaccines might explain these differences in immunogenicity [46]. The difference in immune response observed at month 7 between the two vaccines was sustained up to month 48. However, the long-term clinical implications of these

observed differences in antibody response need to be determined. An anamnestic response was observed after the administration of a fourth dose after 5 years for the quadrivalent vaccine [47] and after 7 years for the bivalent vaccine [48]. In a phase I/II study in South Africa, the bivalent HPV vaccine was shown to Bay 11-7085 be immunogenic and well tolerated in HIV-infected women up to 12 months after vaccination. All subjects, both HIV-positive and HIV-negative were seropositive at month 2, 7 and 12, although antibody titers were lower in HIV-positive children [49]. Similar results were observed with the quadrivalent vaccine [50]. Several studies are currently on-going in HIV-positive adolescent girls and young women to evaluate the safety and immunogenicity of HPV vaccines [17]. Both HPV vaccines have some cross-protection against types that are not included in the vaccines, possibly explained by phylogenetic similarities between L1 genes from vaccine and non-vaccine types: HPV16 is phylogenetically related to HPV types 31, 33, 52 and 58 (A9 species); and HPV18 is related to HPV45 (A7 species).