Kinetics and isotype profile of antibody responses in rhesus macaques induced following vaccination with HPV 6, 11, 16 and 18 L1-virus-like particles formulated with or without Merck aluminum adjuvant

BACKGROUND: Human papillomaviruses (HPV) are the most common sexually transmitted viruses. Infection of the cervical epithelium by HPVs can lead to the development of cervical cancer. Recent advances in vaccine research have shown that immunization with papillomavirus-like particles (VLPs) containing the major structural viral protein, L1 from HPV 16 can provide protection from the establishment of a chronic HPV 16 infection and related cervical intraepithelial neoplasia (CIN) in baseline HPV 16 naive women. METHODS: To better understand the quantitative and qualitative effects of aluminum adjuvant on the immunogenic properties of an HPV 6, 11, 16 and 18L1 VLP vaccine, we used an HPV-specific, antibody isotyping assay and a competitive immunoassay that measures antibodies to neutralizing epitopes to profile sera from rhesus macaques immunized with the HPV L1 VLP vaccine formulated with or without aluminum adjuvant. RESULTS: Immunization with VLPs formulated with the aluminum adjuvant elicited a significantly stronger immune response with higher peak antibody titers both at four weeks post vaccination (12.7 to 41.9-fold higher) as well as in the persistent phase at week 52 (4.3 to 26.7-fold higher) than that of VLPs alone. Furthermore, the aluminum adjuvant formulated HPV VLP vaccine elicited a predominantly T helper type 2 response, with high levels of IgG1 and IgG4 and low levels of IgG2. The vaccine also elicited high levels of serum IgA, which may be important in providing mucosal immunity to impart protection in the anogenital tract. CONCLUSION: These results show that the HPV 6, 11, 16 and 18 L1-VLP vaccine formulated with Merck aluminum adjuvant elicits a robust and durable immune response and holds promise as a vaccine for preventing cervical cancer.     

Enhancing the accuracy of virtual screening: molecular dynamics with quantum-refined force fields

Summary A methodology aimed at improving the accuracy of current docking–scoring procedures is proposed, and validated through detailed tests of its performance in predicting the activity of HIV-1 protease inhibitors. This methodology is based on molecular dynamics simulations using a force field whose effective charges are refined by means of a novel procedure that relies on quantum-mechanical calculations and preserves the internal consistency of the parameterization scheme.     

Electrospray ion-trap multistage mass spectrometry for characterisation of co-monomer compositional distribution of bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) at the molecular level

We report an electrospray ionisation multistage mass spectrometry (ESI-MSn) method that utilises molecular mass information for determination of sequence distribution and chemical structure of mass-selected macromolecules of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) biopolyester, PHBH. On the basis of ESI-MSn studies of PHBH oligomers obtained by partial alkaline depolymerisation of natural PHBH containing 13-14 mol% of hydroxyhexanoate (HH) units, the microstructure of this bacterial copolyester was assessed up to the level of 28 repeat units. The subtle structural details of the PHBH were evaluated based on sequencing of individual macromolecular ions thus showing the utility of this technique for the analysis of biological copolyester macromolecules. It was confirmed that both HH and hydroxybutyrate (HB) units of the PHBH copolymer are randomly distributed.     

Capillary instabilities by fluctuation induced forces

The spontaneous break-up of thin films is commonly attributed to the destabilizing effect of van der Waals forces. Dispersion forces can be considered in terms of the confinement of the electromagnetic fluctuation spectrum. The principle of confinement is more general than the usual argument of interacting dipole fluctuations. It includes also disjoining pressures that are caused by thermal fluctuations. In this context, we review recent publications on the dewetting of thin polymer films, and argue that the presence of an acoustic disjoining pressure is necessary to adequately describe some of these experimental results.Received: 1 August 2003PACS: 47.20.Ma Interfacial instability - 68.15. + e Liquid thin films - 43.25.Qp Radiation pressure     

Insight into the mechanism of three component condensation leading to aminomethylenebisphosphonates

Three-component reaction of a primary amine, diethyl phosphite and triethyl orthoformate followed by acid hydrolysis of the adduct provides N-substituted aminomethylenebisphosphonic acids in good yields. Being extremely versatile, it is commonly utilized for preparation of compounds possessing potential antiosteoporotic, antibacterial, anticancer, antiparasitic or herbicidal activity. However, the mechanism of the reaction remains unknown. p-Nitroaniline has been found an interesting tool to shed light on this matter. Its use allowed to separate and identify four intermediates, both non-phosphorus and phosphorus containing, and subsequently suggest the mechanism of the whole process. The acquired knowledge was helpful in explanation the route and the final product structure obtained for more complex reaction proceeding with the use of 4-aminopyridine. Additional alkylation of the pyridine nitrogen atom, leading to unexpected N-(1-alkylpyridinium-4-amino)methylenebisphosphonic acids was unambiguously proved.     

Coordination modes of 2-mercapto-1,3-benzothiazolate in gallium and indium complexes

2-Mercapto-1,3-benzothiazole (mbztH) may act as a chelating or bridging ligand. In this study, reactions of mbztH with Me₃Ga and Me₃In were examined. The products were characterized by NMR spectroscopy, elemental analyses, melting point, and molecular weight determinations. Formation of mononuclear chelating complexes Me₂M(mbzt) (M = Ga, In) was observed in solutions. Crystallization of Me₂M(mbzt) yielded uncommon non-symmetrical dinuclear complexes Me₄M₂(mbzt)₂, in which one metal is bonded to two sulfurs and the other to two nitrogens.     

Large-scale simulations of a-Si:H: the origin of midgap states revisited

Large-scale classical and quantum simulations are used to generate a-Si:H structures. The bond-resolved density of the occupied electron states discloses the nature of microscopic defects responsible for levels in the gap. Highly strained bonds give rise to band tails and midgap states. The latter originate mainly from stretched bonds, in addition to dangling bonds, and can act as hole traps. This study provides strong evidence for photoinduced degradation (Staebler-Wronski effect) driven by strain, thus supporting recent work on a-Si, and sheds light on the role of hydrogen.     

Calixarene complexes with metal ions

Selected complexes of metal ions are presented showing their syntheses and possible applications, an attention was paid to their usefulness in chemosensors design and in the environmental protection.