Moreover, naïve animals can be protected from subsequent challenge by passive transfer of serum or purified immunoglobulin G (IgG) from L1 VLP immunized animals. Although the correlates of protection have not yet been defined [8] and [9], antibodies are the assumed type-specific immune effectors in humans, wherein protection
against SCH727965 research buy HPV infection is thought to be imparted by serum antibodies that transudate to the genital mucosa [10], [11] and [12]. In addition to HPV types 16 and 18, there are another dozen or so HPV types also associated with cervical disease [2], [3] and [13] and the majority of these belong to the same distinct Alpha-Papillomavirus species groups, A7 (HPV18-related: 39, 45, 59, 68) and A9 (HPV16-related: 31, 33, 35, 52, 58) as the vaccine types [14] and [15]. Emerging clinical trial data suggest that the current HPV vaccines provide a degree of cross-protection against persistent infection and/or high grade lesions (CIN2+) attributed to some of these non-vaccine HPV types, particularly HPV31, 33 and 45, but high throughput screening compounds probably not 52 and 58 [4], [16] and [17]. These findings appear to coincide with limited pre-clinical data showing that HPV16 and 18 VLP can induce low level neutralizing antibodies against genetically related HPV types in small animals [18] and [19]. Few published data
are available on the frequency or titer of neutralizing antibodies raised in vaccinated humans against closely related, non-vaccine types, HPV31, HPV45, HPV52 and HPV58 [20] and [21]. A recent study exploring alternative dosing schedules suggested that there was little difference in vaccine-type antibody titers induced by two or three doses of Gardasil®[22]. The potential impact of a reduced dosing schedule on the induction of vaccine-specific, cross-reactive antibodies is unknown. In this study we have evaluated the propensity for serum from 13 to 14 year old girls immunized with the bivalent vaccine, Cervarix®, within the school-based, UK national
immunization programme, to cross-neutralize pseudoviruses representing a range of A7 and A9 ‘high risk’ HPV types. Anonymized serum samples were collected, following Clomifene informed consent, from 13 to 14 years old girls approximately six months after completion of a three-dose vaccination schedule with the bivalent HPV vaccine, Cervarix®. The vaccines were delivered through the UK’s school-based national HPV Immunization Programme within the recommended dosing intervals [23]. Anonymized serum samples from infants (6 months to 4 years old, males and females) participating in a clinical trial where consent had been given for anonymous testing for other vaccine-related antibodies were used to gauge the potential for non-specific assay interference.
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