Prospects for new human papillomavirus vaccines

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Abstract
Prophylactic human papillomavirus (HPV) L1 virus like particle (VLP) vaccines have been shown, in large randomized controlled clinical trials, to be very immunogenic, well tolerated and highly efficacious against ano-genital disease caused by the vaccine HPV types. However, these vaccines, at the present, protect against only two of the 15 oncogenic genital HPV types, they are expensive, delivered by intramuscular injection and require a cold chain.The challenges are to develop cheap, thermostable vaccines that can be delivered by noninjectable methods that provide long-term (decades) protection at mucosal surfaces to most, if not all, oncogenic HPV types that is as good as the current VLP vaccines. Polyvalent VLP vaccines covering several oncogenic types are in clinical trials. The most promising of the non-VLP second generation vaccines include L1 capsomers and L2 protein and peptides, suitably adjuvanted. Recent data on the mechanism of viral entry and the dynamics of the interaction of the viral capsid proteins L1 and L2 with the cell surface provide a rationale for the protection offered by these new approaches.These second generation vaccines are immunogenic and can provide broad protection but are either at early stage in clinical trial or not in trials. The current VLP prophylactic vaccines are likely to be the only option for the coming decade.