Administration of this HPV-16 vaccine reduced the incidence of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia. Immunizing HPV-16-negative women may eventually reduce the incidence of cervical cancer.

Neutralization of human papillomavirus type 11 (HPV-11) has been demonstrated using serum and cervical secretions from primates vaccinated with virus-like particles (VLPs). Theoretically, neutralizing antibodies could protect women from HPV infection. The immunogenicity of a yeast-derived HPV-11 L1 VLP vaccine was tested in women. Serum specimens were evaluated for HPV-11 titer by competitive radioimmunoassay (cRIA) and for neutralization by use of the athymic mouse xenograft system. Analysis of serum from 104 subjects showed a dose response in HPV-11 cRIA titers and neutralization. Overall, 68 (82.9%) of 82 postimmunization serum specimens from VLP recipients were 100% neutralizing when used in the assay at a 1:50 dilution. Of 69 serum specimens, 63 (91.3%) with cRIA titers 1200 milliMerck units per milliliter were neutralizing. Immunization with HPV VLPs elicits a vigorous serum immune response in a high percentage of women. The HPV-11 cRIA titer appears to be a surrogate marker for neutralization.Human papillomaviruses (HPVs) infect genital, respiratory, and cutaneous epithelia, causing a range of disease states, including genital warts and malignant lesions of the uterine cervix. HPV types 6 and 11 are present in ∼95% of genital warts; HPV types 16, 18, and 31 and other "high-risk" types are present in ∼95% of cervical carcinomas [1,2]. Treatment for most clinically apparent lesions is limited to physical or chemical destruction, which are presumably ineffective treatments, as evidenced by the recurrence rate resulting from insufficient eradication of HPV-infected cells. Therefore, a prophylactic vaccine is needed that could prevent HPV infection.Vaccine development has been slowed by difficulties in propagating HPV in tissue culture and in infecting nonhuman species. Several HPV types have been propagated in the athymic mouse xenograft system [3]. Expression of the L1 gene in yeast results Informed consent was obtained from all patients. Human and animal experimentation guidelines of Indiana University were followed in the conduct of this research. Vaccination of animals with recombinant VLPs has been shown to prevent disease after challenge with the same virus type [6][7][8]. We showed earlier that serum from primates immunized with HPV-11 VLPs neutralized HPV-11 virions [9]. In addition, blood-free cervical secretions collected from the animals partially neutralized . On the basis of these data, the immunogenicity of an HPV-11 VLP (yeast derived) vaccine was evaluated in college-age women. Vaccine was administered in a double-blind, dose-escalating manner. Women who tested negative for HPV types 6 and 11 were vaccinated with HPV-11 VLP vaccine. Serum from each subject was evaluated for antibody titer to HPV-11 and for neutralization of HPV-11 virions. Materials and MethodsVaccination and collection of serum specimens. Women were screened for HPV types 6 and 11 (HPV-6/11) infection by polymerase chain reaction (PCR) analysis of swab samples of multiple anogenital sites. In addition, competitive RIA (cRIA) ...

The proteasome inhibitor bortezomib represents an important advance for the treatment of both previously untreated and treated patients with multiple myeloma (MM). However, nearly all patients eventually relapse or become refractory to bortezomib therapy, so there is a continued need for new therapies. Vorinostat is a potent oral inhibitor of Class I and II histone deacetylases (HDACs) and has demonstrated antiproliferative and proapoptotic activity alone and in combination with bortezomib in preclinical models of MM. Preliminary results from an open-label, multicenter Phase I trial of oral vorinostat in combination with bortezomib have shown that the combination is generally well tolerated and effective in heavily pretreated patients with advanced MM (Weber et al. Haematologica2008;93(S1):0640). Patients (aged ≥18 years with an ECOG performance status 0–2) were sequentially enrolled on escalating doses of vorinostat combination therapy using a standard 3+3 design for ≤8 cycles. Cycles were repeated every 21 days and consisted of vorinostat 200 mg bid or 400 mg daily (Days 1–14) in combination with bortezomib 0.7 or 0.9 mg/m2 i.v. on Days 4, 8, 11, and 15 or escalated to 0.9, 1.1, or 1.3 mg/m2 i.v. on Days 1, 4, 8, and 11. The addition of oral dexamethasone 20 mg on Days 1–4 and 9–12 was allowed for disease progression. We now report the safety and efficacy results for a cohort of patients with relapsed/refactory MM who were previously treated with bortezomib but not within 3 months prior to study enrollment. To date, 13 patients who received prior bortezomib therapy have been enrolled in the trial. Drug-related adverse events (AEs) occurred in 11/13 patients; 90% of these AEs were mild to moderate in severity and 5 patients had serious AEs (7 events). One patient experienced Grade 4 thrombocytopenia, and 8 patients experienced Grade 3 drug-related AEs. The most common drug-related toxicities of any grade were fatigue, nausea and diarrhea. Eleven patients have now discontinued treatment: 6 due to progressive disease and 5 due to AEs. For the 13 patients previously treated with bortezomib, the best response was partial response in 5 patients (duration 99 to 203 days), minimal response in 1 patient (duration 122 days) and stable disease in 7 patients (duration 25 to 320 days). These preliminary data indicate that in this important subset of patients with MM who have relapsed while on, or were refractory to, previous bortezomib therapy, this combination of bortezomib and vorinostat (+/− dexamethasone) administered in a 21-day cycle shows activity, with acceptable tolerability. Further to these promising early findings, data will be presented according to whether patients had relapsed or refractory MM after prior bortezomib. The effect of adding dexamethasone to the combination of vorinostat and bortezomib will also be presented. Supplementary studies in patients clearly resistant to bortezomib are warranted to determine the additional effect of vorinostat in this combination.

In vaccine trials, diary questionnaires or vaccination report cards (VRCs) are used extensively to collect complaints reported by subjects or guardians following vaccination. These have not been evaluated for accuracy or standardized to facilitate tolerability comparisons among vaccines. Objectives —(1) Develop standardized, age‐specific VRCs for collecting self‐reported adverse events (AEs) in trials; (2) Evaluate whether complaints elicited by nurse examinations or telephone interviews were missed by VRCs. Methods —Vaccine‐trial databases, focus groups, experts and experienced nurses were used to develop paediatric and adolescent/adult VRCs. VRCs were evaluated at four sites. The primary outcome was subjects with AEs missed on the VRC and reported in nurse examinations (for injection‐site reactions) or telephone interviews (for systemic complaints). Results —Of 855 subjects, 96.5% completed VRCs. For systemic complaints, 1.5% (12/812) reported both no complaint on VRCs and at least one complaint in telephone interviews. For injection‐site reactions, 5.1% (53/1030) of injection sites had both no reaction reported on VRCs and had reactions noted by nurse examination. No missed AEs were rated as severe. Conclusion —The data suggest VRCs provide a practical and reasonably complete method of eliciting complaints following vaccination. Copyright © 2000 John Wiley & Sons, Ltd.

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