Immunogenicity and tolerability of an MF59-adjuvanted, egg-derived, A/H1N1 pandemic influenza vaccine in children 6-35 months of age

Background: Vaccines against pandemic A/H1N1 influenza should provide protective immunity in children, because they are at greater risk of disease than adults. This study was conducted to identify the optimal dose of an MF59 (R)-adjuvanted, egg-derived, A/H1N1 influenza vaccine for young children. Methods: Children 6-11 months (N = 144) and 12-35 months (N = 186) of age received vaccine formulations containing either 3.75 mu g antigen with half the standard dose of MF59 or 7.5 mu g antigen with a standard dose of MF59, or a nonadjuvanted formulation containing 15 mu g antigen (children 12-35 months only). Participants were given 2 primary vaccine doses 3 weeks apart, followed by 1 booster dose of MF59-adjuvanted seasonal influenza vaccine 1 year later. Immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. Results: All vaccine formulations were highly immunogenic and met all 3 European licensure criteria after 2 doses. MF59-adjuvanted vaccines met all licensure criteria after 1 dose in both age cohorts, while nonadjuvanted vaccine did not meet all criteria after 1 dose in children 12-35 months. A single booster dose was highly immunogenic, and stable antibody persistence was observed in response to all vaccines. All vaccines were well tolerated. Conclusions: In this study, a single dose of 3.75 mu g antigen with half the standard dose of MF59 was shown to be optimal, providing adequate levels of immediate and long-term antibodies in pediatric subjects 6-35 months of age. These data demonstrated that MF59 adjuvant allowed for reduced antigen content and promoted significant long-term antibody persistence in children, with a satisfactory safety profile

Impact and cost-effectiveness of different vaccination strategies to reduce the burden of pneumococcal disease among elderly in the Netherlands

BACKGROUND: Streptococcus pneumoniae causes morbidity and mortality among all ages in The Netherlands. To reduce this burden, infants in The Netherlands receive the 10-valent pneumococcal conjugated vaccine (PCV10), but older persons are not targeted. We assessed the impact and cost-effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) or 13-valent PCV (PCV13) among all those aged 60, 65 or 70 and/or in combination with replacing PCV10 with PCV13 in the infant vaccination programme.METHODS: A static cost-effectiveness model was parameterized including projected trends for invasive pneumococcal disease (IPD) and hospitalised community acquired pneumonia (CAP). The different strategies were evaluated using vaccine list prices and a 10-year time horizon. Incremental cost-effectiveness ratios (ICER) were calculated with the current strategy (infant vaccination program with PCV10) as reference.RESULTS: Compared to the reference, the largest impact on pneumococcal disease burden was projected with a combined use of PCV13 among infants and PPV23 at 60, 65 and 70 years, preventing 1,635 cases of IPD and 914 cases of CAP. The most cost-effective strategy was vaccinating with PPV23 at 70 years only with similar low ICERs at age 60 and 65. The impact of the use of PCV13 among infants depends strongly on the projected herd-immunity effect on serotype 19A. Vaccinating elderly with either PCV13 or PPV23 was dominated by PPV23 in all investigated scenarios, mainly due to the lower price of PPV23.CONCLUSION: Under the current assumptions, the best value for money is the use of PPV23 for elderly, with a single dose or at five year increment between age 60 to age 70.</p

Reemergence of pertussis in the highly vaccinated population of the Netherlands: observations on surveillance data.

We analyzed pertussis reporting, death, hospitalization, and serodiagnostic data from 1976 to 1998 to help explain the cause of the 1996 pertussis outbreak in the Netherlands. The unexpected outbreak was detected by an increase in pertussis reporting and by other surveillance methods. In 1996, according to reporting and serologic data, the increase in pertussis incidence among (mostly unvaccinated) children less than 1 year of age was similar to the increase in hospital admissions. Among older (mostly vaccinated) persons, the increase in hospital admissions was relatively small. The increase in pertussis incidence was higher among vaccinated than among unvaccinated persons of all ages. This resulted in lower estimates of vaccine effectiveness. The proportion of pertussis infections resulting in recognizable symptoms may have increased among vaccinated persons because of a mismatch of the vaccine strain and circulating Bordetella pertussis strains. The small immunogenicity profile of the Dutch vaccine may have resulted in greater vulnerability to antigenic changes in B. pertussis

Pertussis in The Netherlands: an outbreak despite high levels of immunization with whole-cell vaccine.

In 1996, a sudden increase in pertussis incidence was reported in the Netherlands (2.1 per 100,000 in 1995, 18 per 100,000 in 1996). Although not all potential surveillance artifacts could be excluded, it is highly probable that the data reflect a true outbreak. However, the cause of this increase has not yet been determined. Further research is directed to the severity of disease and a possible mismatch between the vaccine and the circulating Bordetella strains

Особенности художественного отображения агрессии, направленной против Азербайджана

[EN]: The micromammals remains from the Late Pleistocene site of the cave of El Castillo studied here in detail, came from the Aurignacian levels 18b and 18c (dated in 40.000-45.000 BP), level 19, and the Musterian levels 20b, 20c, 20d, 20e (dated in 41.000-49.000 BP), 21a and 21b. The micromammal association is the following: Erinaceus europaeus, Crocidura russula, Sorex coronatus, Sorex minutus, Neomys fodiens, Talpa europaea, Galemys pyrenaicus, cf. Miniopterus schreibersii, Chiroptera indet., Pliomys lenki, Microtus arvalis – Microtus agrestis, Microtus lusitanicus, Microtus oeconomus, Chionomys nivalis, Arvicola terrestris, Apodemus sylvaticus – Apodemus flavicollis and Lepus sp. Most of these species are in the present fauna of Cantabria, except Pliomys lenki that got extinct in the last third of the Upper Pleistocene, and Microtus oeconomus that disappeared from the Iberian Peninsula during the Holocene, in historical times, and is nowadays present in northern Euroasiatic regions. There is a great continuity of most of the taxa in all the levels. The faunal association seems to indicate a mainly open environment, in general with wet meadows (and few dry meadows), with good vegetation cover in the soil, with perhaps also some tree-covered areas, and some watercourses. The thermophiles indicators are very scarce, which could indicate that the climate could be a lesser temperate than other Upper Pleistocene periods and the present-day climate in the area.[ES]: El material de micromamíferos del yacimiento del Pleistoceno Superior de la cueva de El Castillo, objeto de estudio detallado en este trabajo, proviene de los niveles auriñacienses 18b y 18c (datados en 40.000-45.000 BP), nivel 19, y niveles musterienses 20b, 20c, 20d, 20e (datados en 41.000-49.000 BP), 21a y 21b. La asociación de micromamíferos es la siguiente: Erinaceus europaeus, Crocidura russula, Sorex coronatus, Sorex minutus, Neomys fodiens, Talpa europaea, Galemys pyrenaicus, cf. Miniopterus schreibersii, Chiroptera indet., Pliomys lenki, Microtus arvalis – Microtus agrestis, Microtus lusitanicus, Microtus oeconomus, Chionomys nivalis, Arvicola terrestris, Apodemus sylvaticus – Apodemus flavicollis y Lepus sp. La mayoría de estas especies están presentes en la fauna actual de Cantabria, excepto Pliomys lenki que se extinguió en el último tercio del Pleistoceno Superior, y Microtus oeconomus, que persistió en la península ibérica durante el Holoceno bien avanzado hasta su desaparición en tiempos históricos, y que actualmente está en regiones euroasiáticas más septentrionales. Hay una gran continuidad de la gran mayoría de los taxones en todos los niveles. La fauna en su conjunto parece indicar un medio predominantemente abierto, por lo general de praderas húmedas (y en mucha menor medida praderas secas) con una buena cobertura vegetal a nivel del suelo, en el que habría también algunas zonas arboladas o boscosas, y algún curso de agua. Los indicadores termófilos son escasos y poco abundantes, lo que podría indicar que el clima podría ser algo menos templado que en otros periodos del Pleistoceno Superior y quizás también que actualmente en la zona.Peer Reviewe

Rapid Immunization Against H5N1: A Randomized Trial Evaluating Homologous and Cross-Reactive Immune Responses to AS03A-Adjuvanted Vaccination in Adults

Background. Accelerated immunization schedules may help gain early control of influenza pandemics. We investigated different schedules of an AS03A-adjuvanted H5N1 vaccine

A standardized framework for the validation and verification of clinical molecular genetic tests

The validation and verification of laboratory methods and procedures before their use in clinical testing is essential for providing a safe and useful service to clinicians and patients. This paper outlines the principles of validation and verification in the context of clinical human molecular genetic testing. We describe implementation processes, types of tests and their key validation components, and suggest some relevant statistical approaches that can be used by individual laboratories to ensure that tests are conducted to defined standards

Immunogenicity Profile of a 3.75-μg Hemagglutinin Pandemic rH5N1 Split Virion AS03A-Adjuvanted Vaccine in Elderly Persons: A Randomized Trial

Background. Elderly persons often experience a reduced immune response to influenza vaccination. We evaluated the usual dose of AS03A-adjuvanted H5N1 pandemic vaccine (3.75 μg hemagglutinin of A/Vietnam/1194/2004-like strain) compared with a double dose in an elderly population