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Ensuring complete viral inactivation is critical for the safety of vaccines based on an inactivated virus. Detection of residual infectious virus is dependent on sensitivity of the assay, sample volume analyzed and the absence of interference with viral infection. Here we describe the development and qualification of a sensitive cell-based assay for the detection of residual infectious West Nile Virus (WNV). The results of the assay are in good agreement with the assumption that at low concentrations the number of infectious units in relatively small samples follows a Poisson distribution. The assay can detect 1 infectious unit with a confidence of 99%, provides statistical controls for interference and can easily be scaled up to test large amounts of vaccine material. Furthermore, we show equivalence in sensitivity between the cell-based assay and an in vivo assay for detection of infectious WNV. Finally, the assay has been used for successful release testing of clinical lots of inactivated WNV vaccine. Given the principle and generic setup of the method we envision broad applicability to the detection of very low concentrations of infectious virus.

Background The use of human papillomavirus (HPV) vaccines has been universally approved for women from age 12 to 25 years, but those older than 16 years receive no reimbursement for the cost of the vaccine in the Netherlands. Reductions in the vaccine price as well as new insights in the efficacy of HPV vaccines offer renewed arguments to consider HPV vaccination in adult women. We calculated the clinical benefit and cost-effectiveness of vaccinating women aged 17–25 years in 2010. Methods The calculations were based on an individual-based simulation model for cervical carcinogenesis, with HPV infection risks obtained from a type-specific HPV transmission model. The indirect protective effect from vaccinating 12 to 16 year-old girls was adjusted for. Cervical screening in the model was incorporated according Dutch screening guidelines, i.e. 7 cytology-based rounds at 5-year intervals from the age of 30. As base-case, we assumed the vaccine to offer full protection against HPV16/18 only if no prior exposure to that type had occurred before vaccination. In sensitivity analyses, we considered partial cross-protection against types 31/33/45/58 and efficacy against all future infections, irrespective of previous or current infection status. Results In base-case analyses, vaccinating 17 year-olds reduced their lifetime risk of treatment for precancerous lesions from 7.77% to 3.48% and their lifetime cervical cancer risk from 0.52% to 0.24%. These risks were 6.12% and 0.45%, respectively, for a 25 year-old vaccinee. The incremental cost-effectiveness ratio (ICER) for vaccinating 17–25 year-olds was €22,526 per quality-adjusted life-year (QALY) at a vaccine price of €65 per dose, a 50% reduction of the 2010 pharmacy price in the Netherlands. If cross-protection against types 31/33/45/58 was included, the ICER decreased to €14,734 per QALY. Results were robust to efficacy assumptions with respect to previous or current infection status. Conclusion The clinical benefit of HPV vaccination of women up to 25 years moderately depends on cross-protection to non-vaccine types. Refunding the cost of the vaccine to 17–25 year-old women in the Netherlands can be considered cost-effective at anticipated price reductions.