D

D. HPV6-seropositive sera from women enrolled in a study of incident HPV contamination. Twelve sera were HPV6 specific, while the remainder reacted with both HPV6 and HPV11 L1. By preadsorption studies, 6/11 of these sera were shown to be cross-reactive. Among the HPV6-specific sera there was no immunodominant epitope recognized by all sera. Six of the 12 sera acknowledged epitopes that contained residues from combinations of the BC, DE, and FG loops, one serum acknowledged an epitope that consisted partially of the C-terminal arm, and three sera acknowledged complex epitopes to which reactivity was eliminated by switching all five loops. Reactivity in two sera was not eliminated even with all six regions swapped. The patterns of epitope recognition did not change over time in women whose sera were examined 9 years after their first-seropositive visit. Human papillomavirus (HPV) contamination of the genital tract is one of the most common sexually transmitted diseases (6). From 50 to 75% of sexually active individuals will be infected by genital HPVs in their lifetime (14). HPV infects the epithelium and causes aberrant cellular proliferation. This can potentially lead to benign genital warts, as seen with the low-risk HPV type Ecteinascidin-Analog-1 6 (HPV6) and HPV11, or to cervical cancer, seen with high-risk HPV types 16 and 18. Given that cervical cancer is still a leading cause of malignancy deaths for women worldwide, eliminating genital HPV infections would have a significant public health impact. Although HPVs cannot be easily cultured because infectious computer virus production is linked to epithelial cell differentiation, virus-like particles (VLPs) can be purified from the expression of the major capsid protein (L1) in eukaryotic cells (18, 25, 28, 31, 41). The major capsid protein self-assembles into a T = 7 icosahedral VLP composed of Ecteinascidin-Analog-1 72 L1 pentamers (capsomers). VLPs are structurally and immunologically similar to infectious computer virus as gauged by electron microscopic imaging studies, and their ability to bind type-specific, conformation-dependent monoclonal antibodies (MAbs). Consequently, experimental vaccines have tested the efficacy of immunizing with VLPs in animal models of papillomaviruses (2, 29, 45) and in humans (19, 32). Ecteinascidin-Analog-1 Type-specific, conformation-dependent antibodies made in response to VLP vaccination do indeed protect animals against infectious viral challenge (27, 29, 45) and neutralize computer virus in in vitro assays (27). Protection against infection has been attributed to the humoral immune response since passive transfer of serum from immunized animals to untreated animals protects the recipient against infectious viral challenge (2). Immunizing with capsomers also protects against infectious viral challenge, since capsomers have been shown to contain the epitopes found on VLPs that are recognized by neutralizing monoclonal antibodies (MAbs) (42, 54). A clinical trial of an HPV16 VLP-based vaccine was shown to be 100% effective in protecting women from persistent HPV16 contamination and pathology (32). Another recent clinical trial of bivalent VLP vaccine also showed impressive efficacy in protecting SPP1 against infection and associated pathology from HPV16 and HPV18 (19). Despite the ongoing vaccine trials, little is known about the epitopes around the computer virus or VLPs that are acknowledged in response to natural infection or following vaccination. Initial epitope mapping used type-specific MAbs to define regions of L1 critical for MAb binding. Some studies suggest the presence of type-specific immunodominant epitopes. Residues 131 to 132 of HPV11 L1 confer type specificity (34) and are thought to be immunodominant as these residues had to be altered to further uncover additional HPV11 L1 regions critical for binding MAbs (35, 36). Comparable studies with HPV6 L1 also support the presence of an immunodominant epitope, as altering HPV6 L1 residues 49 and 54 obliterates binding of the majority of HPV6 L1 type-specific MAbs (37, 48). Yet it is not known Ecteinascidin-Analog-1 if residues Ecteinascidin-Analog-1 critical for binding MAbs are also the regions recognized by human antibodies, or whether the human antibody response also targets a single immunodominant epitope. One study concluded that human antibodies acknowledged a single immunodominant epitope because incubating a.