http://repub.eur.nl/res/aut/2267/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39045/ 2012-09-01T00:00:00Z Each year, influenza viruses cause epidemics by evading pre-existing humoral immunity through mutations in the major glycoproteins: the haemagglutinin (HA) and the neuraminidase (NA). In 2004, the antigenic evolution of HA of human influenza A (H3N2) viruses was mapped (Smith et al., Science 305, 371-376, 2004) from its introduction in humans in 1968 until 2003. The current study focused on the genetic evolution of NA and compared it with HA using the dataset of Smith and colleagues, updated to the epidemic of the 2009/2010 season. Phylogenetic trees and genetic maps were constructed to visualize the genetic evolution of NA and HA. The results revealed multiple reassortment events over the years. Overall rates of evolutionary change were lower for NA than for HA1 at the nucleotide level. Selection pressures were estimated, revealing an abundance of negatively selected sites and sparse positively selected sites. The differences found between the evolution of NA and HA1 warrant further analysis of the evolution of NA at the phenotypic level, as has been done previously for HA. http://repub.eur.nl/res/pub/34460/ 2011-09-01T00:00:00Z The emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalent MF59-adjuvanted vaccine, as well as the persistence of vaccine-induced antibodies. Our prospective longitudinal study included 498 health care workers (mean age, 43 years; median age, 44 years). Most (89%) had never or only occasionally received a seasonal influenza virus vaccine, and 11% were vaccinated annually (on average, for >10 years). Antibody titers were determined by a hemagglutination inhibition (HI) assay at baseline, 3 weeks after the first vaccination, and 5 weeks and 7 months after the second vaccination. Four hundred thirty-five persons received two doses of the 2009 vaccine. After the first dose, 79.5% developed a HI titer of ≥40. This percentage increased to 83.3% after the second dose. Persistent antibodies were found in 71.9% of the group that had not received annual vaccinations and in 43.8% of the group that had received annual vaccinations. The latter group tended to have lower HI titers (P = 0.09). With increasing age, HI titers decreased significantly, by 2.4% per year. A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted. Copyright http://repub.eur.nl/res/pub/31508/ 2011-03-01T00:00:00Z Background: This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment. Patients and methods: We investigated the influence of methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) and methionine synthase reductase (MTRR 66A>G) single nucleotide polymorphisms (SNPs) on total body BMD (BMDTB) and lumbar spine BMD (BMDLS) in 83 patients. Homocysteine, folate and vitamin B12 were determined. BMD was measured repeatedly using dual-energy X-ray absorptiometry in patients ≥4years (n=68). Results: Carriers of the MTHFR 677 T-allele showed a lower baseline BMDTBthan non-carriers (-0.38 SDS vs. +0.55 SDS, p=0.01) and BMDTBremained lower during/after treatment. MTHFR 677C>T did not influence treatment-related loss of BMDTB(p=0.39). The MTRR 66 G-allele carriers showed a trend towards a lower BMDTBcompared with non-carriers. Combining these two SNPs, patients carrying ≥2 risk alleles had a significantly lower BMDTB(-1.40 SDS) than patients with one (-0.80 SDS) or no risk alleles (-0.31 SDS). Although carriers of the MTHFR 1298A>C had higher homocysteine levels, this SNP was not related to BMDTB. BMDLSof carriers was similar to non-carriers of the investigated SNPs. Conclusions: The MTHFR 677C>T SNP and the MTRR 66A>G SNP were identified as determinants of impaired BMDTBin childhood ALL patients. http://repub.eur.nl/res/pub/3808/ 2001-10-12T00:00:00Z Since the production of influenza vaccines is complicated by the continuous variation of these viruses, it would be desirable to develop vaccines that induce cross-protective immunity against influenza virus strains that circulate in subsequent winter epidemics. We have recently demonstrated that antibodies induced after vaccination with an immune stimulating complex (ISCOM)-based vaccine exhibited a certain degree of cross-reactivity with other influenza virus strains. In the present study, ISCOM-based vaccines were evaluated retrospectively by testing the protective immunity induced by ISCOM prepared with the membrane glycoproteins of A/Philippines/2/82 against the more recent strain A/Netherlands/18/94 in monkeys with or without a history of prior infection with an A/Philippines/2/82-like virus. It was found that the monkeys immunized with the A/Philippines/2/82 ISCOM were not protected from challenge infection with A/Netherlands/18/94. On the other hand, vaccination of monkeys which experienced a prior infection with an influenza A/Philippines/2/82-like virus, with a single dose of ISCOM vaccine induced long-lasting protective immunity against challenge infection with the homologous virus A/Netherlands/18/94 http://repub.eur.nl/res/pub/9476/ 2000-01-01T00:00:00Z Respiratory syncytial virus group A strain variations of 28 isolates from The Netherlands collected during three consecutive seasons were studied by analyzing G protein sequences. Several lineages circulated repeatedly and simultaneously during the respective seasons. No relationships were found between lineages on the one hand and clinical severity or age on the other. http://repub.eur.nl/res/pub/15032/ 1993-01-01T00:00:00Z In the autumn of 1992 two-thirds of the population of a nursing home in Amsterdam was vaccinated against influenza. However, in March 1993 an outbreak of an influenza like illness occurred with a morbidity rate of 49% and a mortality rate of 10%. There was sufficient serological evidence to show that the vaccine as such had induced adequate immunity. As the causative agent an influenza A/H3N2 virus was identified. The failing activity of the vaccine in this instance was apparently caused by the absence of sufficient antigen similarity between the A/H3N2 vaccine component and the epidemic virus ('vaccine mismatch').