Papillomaviruses, members of the Papoviridae family, are species-specific, non-enveloped icosahedral DNA viruses which cause squamous epithelial and fibroepithelial tumors in their hosts. Over 70 distinct types have been isolated from human tissue samples alone, with the most serious consequences of infection being the development of cervival cancer. Recently it has been shown that recombinant expression of the major capsid protein, L1, results in the production of non-infectious virus-like particles (VLPs) which mimic the structure of virions and elicit antibody responses similar to those induced by the virus itself. This provides an opportunity to develop prophylactic vaccines to limit or prevent infection. Because these vaccines are intended to induce protective humoral responses, it is important to understand the immune responses elicited by virus and VLPs. Early studies identified several linear epitopes in L1, some cross-reactive among serotypes, others type-specific. More recent data have shown that the protective epitopes are type-specific and dependent upon an assembled particle for proper conformation. It further appears that highly-divergent amino acid sequences, located at similar positions within the L1 proteins of the different serotypes, are responsible for the induction of these conformationally dependent, protective responses. This article reviews work which leads to this understanding of the humoral responses to papillomavirus and VLPs.
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