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G F Rimmelzwaan

Publications and source records attributed to G F Rimmelzwaan.

At least 19 recordsLinked to original sources
PubMed2006

[The 2005-2006 influenza season in the Netherlands and the vaccine composition for the 2006-2007 season].

The first sign of influenza activity in the Netherlands during the 2005-2006 influenza season was the isolation of influenza viruses in the last week of 2005. From Week 1 of 2006 onwards, an increase in clinical influenza activity was also observed that did not return to baseline levels until Week 15. Two waves of influenza activity were observed with peak incidences of 13.8 and 9.8 influenza-like illnesses per 10,000 inhabitants on Weeks 7 and 12, respectively. The first wave of influenza was caused primarily by influenza B viruses, whereas the second wave was caused predominantly by influenza A/H3N2 viruses. The influenza B viruses appeared to belong to two different phylogenetic lineages and were antigenically distinguishable from the vaccine strain. The isolated influenza A/H3N2 viruses were closely related to the vaccine strain for this subtype and only minor antigenic differences with the vaccine strain were observed for a limited number of isolates. Only a small number of influenza A/H1N1 viruses were isolated, which all closely resembled the H1N1 vaccine strain. For the 2006-2007 influenza season, the World Health Organization has recommended the following vaccine composition: A/Wisconsin/67/05 (H3N2), A/New Caledonia/20/99 (H1N1) and B/Malaysia/2506/05.

Disease Outbreaks↗
PubMed2006

Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice.

In order to assess the level of protection against a lethal influenza virus infection provided by a primary infection with a virus strain of another subtype, C57BL/6 mice were infected with the sublethal influenza virus X-31 (H3N2) and subsequently challenged with the lethal strain A/PR/8/34 (H1N1). The outcome of the challenge infection was compared with that in mice that did not experience an infection with influenza virus X-31 prior to the challenge infection. The X-31 experienced mice cleared the infection with influenza virus A/PR/8/34 in an accelerated fashion, displayed less clinical signs and a reduction of lesions in the lungs resulting in improved survival rates of these mice compared to the naive mice. The improved outcome of the challenge infection with influenza virus A/PR/8/34 in the X-31 experienced mice correlated with priming for anamnestic virus-specific CD8(+) cytotoxic T lymphocyte (CTL) responses as was demonstrated by the detection of CTL specific for the H-2D(b) restricted NP(366-374) epitope that was shared by the influenza viruses X-31 and A/PR/8/34. Thus previous exposure to influenza A viruses affords partial protection against infection in the absence of virus-neutralizing antibodies specific for the hemagglutinin and the neuraminidase. The implications of these observations are discussed in the light of the current pandemic threat and development of vaccines that aim at the induction of virus-specific CTL.

Animals↗
PubMed2006

Fitness costs limit escape from cytotoxic T lymphocytes by influenza A viruses.

The use of cytotoxic T lymphocyte (CTL)-inducing vaccines could afford both homo- and heterosubtypic immunity. However, amino acid variation in CTL epitopes associated with escape from CTL-mediated immunity might undermine the use of these vaccines. To assess the impact of amino acid substitutions in highly conserved epitopes on viral fitness and recognition by specific CTL, we performed a mutational analysis of various CTL epitopes. Our findings indicated that fitness costs limited variation in functionally constrained epitopes, especially at anchor residues.

Amino Acid Sequence↗
PubMed2005

[The influenza season 2004/'05 in the Netherlands with the largest epidemic of the last 5 years caused by the virus variant A/California and the composition of the vaccine for the season 2005/'06].

In the Netherlands, the influenza epidemic of the 2004/'05 season started late. The background value of 3 cases of an influenza-like illness per 10,000 inhabitants per week was exceeded from week 1 until week 14 of 2005. The magnitude of the epidemic was the largest of the last 5 years, namely 104 per 10,000 inhabitants. As usual, the epidemic was caused mainly by influenza-A viruses of subtype H3N2 and to a lesser degree by A/H1N1 and B viruses. The H3N2-virus isolates belonged to the newly emerged variant A/California/7/04, which deviated slightly from the vaccine strain used for the 2004/'05 season. The influenza-B and H1N1 viruses matched the corresponding vaccine viruses well. For the 2005/'06 season, the World Health Organization has recommended the following vaccine composition: A/California/7/04 (H3N2), A/New Caledonia/20/99 (HiNI), and B/Shanghai/361/02.

Global Health↗
PubMed2005

Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants.

Amino acid substitutions have been identified in the influenza A virus nucleoprotein that are associated with escape from recognition by virus-specific cytotoxic T lymphocytes (CTLs). One of these is the arginine-to-glycine substitution at position 384 (R384G). This substitution alone, however, is detrimental to viral fitness, which is overcome in part by the functionally compensating co-mutation E375G. Here, the effect on viral fitness of four other co-mutations associated with R384G was investigated by using plasmid-driven rescue of mutant viruses. Whilst none of these alternative co-mutations alone compensated functionally for the detrimental effect of the R384G substitution, the M239V substitution improved viral fitness of viruses containing 375G and 384R. The nucleoprotein displays unexpected flexibility to overcome functional constraints imposed by CTL epitope sequences, allowing influenza viruses to escape from specific CTLs.

Amino Acid Substitution↗
PubMed2005

Functional profile of human influenza virus-specific cytotoxic T lymphocyte activity is influenced by interleukin-2 concentration and epitope specificity.

The ability of influenza A virus-specific cytotoxic T lymphocytes (CTL) to degranulate and produce cytokines upon antigenic restimulation was studied in four HLA-A*0101 and HLA-A*0201 positive subjects. Peripheral blood mononuclear cells of these subjects were stimulated with influenza A virus in the presence of high or low interleukin (IL)-2 concentrations. CD8(+) T cell populations specific for the HLA-A*0101 restricted epitope NP(44-52) and the HLA-A*0201 restricted epitope M1(58-66) were identified by positive staining with tetramers of peptide major histocompatibility complexes (MHC) (NP-Tm and M1-Tm, respectively). Within these populations, the proportion of cells mobilizing CD107a, or expressing interferon (IFN)-gamma and tumour necrosis factor-(TNF)-alpha upon short-term peptide restimulation was determined by flow cytometry. Independent of IL-2 concentrations, large subject-dependent differences in the mobilization of CD107a and expression of IFN-gamma and TNF-alpha by both NP- and M1-specific T cells were observed. In two of the four subjects, the functional profile of NP-Tm(+) and M1-Tm(+) cells differed considerably. Overall, no difference in the proportion of NP-Tm(+) or M1-Tm(+) cells expressing CD107a was observed. The proportion of M1-Tm(+) cells that produced IFN-gamma (P < 0.05) was larger than for NP-Tm(+) cells, independent of IL-2 concentration. When cultured under IL-2(hi) concentrations higher TNF-alpha expression was also observed in M1-Tm(+) cells (P < 0.05). The IL-2 concentration during expansion of virus-specific cells had a profound effect on the functionality of both M1-Tm(+) and NP-Tm(+) cells.

Adult↗
PubMed2005

Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes.

Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in CTL epitopes. Also for influenza A viruses a number of amino acid substitutions in the nucleoprotein (NP) have been associated with escape from CTL. However, other previously identified influenza A virus CTL epitopes are highly conserved, including the immunodominant HLA-A*0201-restricted epitope from the matrix protein, M1(58-66). We hypothesized that functional constraints were responsible for the conserved nature of influenza A virus CTL epitopes, limiting escape from CTL. To assess the impact of amino acid substitutions in conserved epitopes on viral fitness and recognition by specific CTL, we performed a mutational analysis of CTL epitopes. Both alanine replacements and more conservative substitutions were introduced at various positions of different influenza A virus CTL epitopes. Alanine replacements for each of the nine amino acids of the M1(58-66) epitope were tolerated to various extents, except for the anchor residue at the second position. Substitution of anchor residues in other influenza A virus CTL epitopes also affected viral fitness. Viable mutant viruses were used in CTL recognition experiments. The results are discussed in the light of the possibility of influenza viruses to escape from specific CTL. It was speculated that functional constraints limit variation in certain epitopes, especially at anchor residues, explaining the conserved nature of these epitopes.

Amino Acid Substitution↗
PubMed2004

[The 2003/2004 influenza season in the Netherlands with a limited epidemic of the virus variant A/Fujian, and the vaccine composition for the 2004/2005 season].

In contrast to the three previous influenza seasons, the influenza epidemic of the 2003/2004 season started early in week 49 of 2003. The epidemic was predominantly caused by influenza-A viruses of the H3N2 subtype. All isolated influenza-A viruses were antigenically related to influenza virus A/Fujian/411/02, which was already detected in the influenza season 2002/2003 and that deviated from the vaccine-reference strain A/Moscow/10/99 to a certain extent. The magnitude of the epidemic was limited despite the fact that it was caused by influenza-A H3N2-virus-drift variants. Immunity caused by natural infection with influenza viruses during previous seasons or vaccination has possibly provided sufficient cross protection against these new H3N2-drift variant. No influenza-A viruses of the H1N1 or H1N2 subtypes were detected in the influenza season 2003/2004. Only a small number of influenza-B viruses were isolated, which all belonged to the B/Yamagata/16/88 lineage, which was temporarily replaced by the B/Victoria2/87 lineage in the previous influenza season. On the basis of epidemiological and serological data the World Health Organization has recommended the following vaccine composition for the 2004/2005 influenza season: A/Fujian/411/02 (H3N2), A/New Caledonia/20/99 (H1N1) and B/Shanghai/361/02.

Global Health↗
PubMed2004

Human airway epithelial cells present antigen to influenza virus-specific CD8+ CTL inefficiently after incubation with viral protein together with ISCOMATRIX.

In the present paper, an in vitro model was established in which the interaction between influenza virus-specific CD8+ T cells and human airway epithelial cells can be studied. To this end, the human lung epithelial cell line A549 was transduced with the HLA-A*0201 gene. This MHC class I allele is involved in the presentation of the immunodominant M158-66 cytotoxic T lymphocyte (CTL) epitope of the influenza A virus matrix protein. The A549-HLA-A2 cells and a CD8+ T cell clone specific for the M158-66 epitope were used to evaluate ISCOMATRIX (IMX), which is considered a potential mucosal adjuvant for influenza vaccines, for its capacity to activate virus-specific CTL after incubation with epithelial cells. It was found that virus infected epithelial cells activated virus-specific CTL efficiently. However, incubation of epithelial cells with ISCOMATRIX and recombinant M1 protein activated CD8+ T cells inefficiently, unlike the incubation of C1R cells expressing a HLA-A2 trans gene or HLA-A2+ B-lymphoblastoid cells with these reagents. It was concluded that this lack of antigen presentation by epithelial cells indicate that these cells are not subject to killing by virus-specific CTL upon instillation with ISCOMATRIX-based vaccines, which may be a favorable property of mucosal vaccines.

Adjuvants, Immunologic↗
PubMed2004

Impaired response rates, but satisfying protection rates to influenza vaccination in dialysis patients.

Dialysis patients show impaired responses to several vaccines. Limited recent data are available on influenza vaccination in these patients. In the 1998-1999 influenza season, 44 dialysis patients received a standard trivalent vaccination followed by a booster two months later. The serum antibody responses in these patients were compared with those found in healthy subjects. A fourfold rise in serum hemagglutination inhibition titre was achieved in 23-58% of all patients. Protective titres were reached in 53-93% of the patients. Since protective antibody titers can be induced, it is recommended to vaccinate dialysis patients annually against influenza.

Aged↗
PubMed2004

[Neuraminidase inhibitors oseltamivir and zanamivir: new means of defence against influenza].

Recently two new neuraminidase inhibitors zanamivir and oseltamivir have been marketed. They appear to considerably reduce morbidity and mortality from influenza. Their adverse effects are infrequent and mild and the chance of development of pathogenically significant resistant mutants appears to be small. During the first six months of a pandemic, neuraminidase inhibitors are the only defence against the virus. It is therefore important to stockpile in each country sufficient quantities of these drugs. During the usual influenza epidemics the main value of neuraminidase inhibitors lies in their use for therapy, prophylaxis and post-exposure prophylaxis in long-term care institutions for the elderly (for prophylaxis only oseltamivir is licensed). Although data on the effectiveness against complications of influenza and on the effect on people with an increased risk of (fatal) complications as a result of an influenza virus infection are limited, the available information on the effects of the neuraminidinase inhibitors indicates that these drugs will also protect against complications and that high-risk groups will benefit from the rapid deployment of these products. The cost-effectiveness of treatment and post-exposure prophylaxis with neuraminidinase inhibitors is probably not favourable for healthy children and adults but seems to be favourable for the high-risk groups (vaccinated or not) in winter.

Acetamides↗
PubMed2004

Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes.

CD8+ cytotoxic T lymphocytes (CTLs) contribute to the control of viral infections by recognizing peptides of viral proteins presented by MHC class I molecules on infected cells. Some viruses have developed strategies to evade recognition by CTL. One of these strategies involves antigenic variation in CTL epitopes as described for viruses chronically infecting their host like EBV, HIV, HBV and HCV. Here we show three examples of variation in CTL epitopes in the influenza virus nucleoprotein (NP) associated with escape from CTL immunity. The first two involve a mutation at position 384 of the NP, which is the anchor residue of a HLA-B*2705-restricted epitope NP383-391 (SRYWAIRTR) and the HLA-B*08-restricted epitope NP380-388 (ELRSRYWAI). It was shown that these mutations have arisen in the 1993/1994 season and that these mutant variants completely replaced the virus strains containing the wild-type epitopes. Furthermore, T cell recognition was completely abrogated by the R384G mutation. A third example of variation in an influenza virus CTL epitope was found in a newly identified HLA-B*3501-restricted CTL epitope. This immunodominant epitope exhibited extensive amino acid sequence variation and the variants emerged in a chronological order. Again CTL specific for older variants failed to recognize more recent strains of influenza A virus, indicating an escape from CTL immunity. Thus, in addition to the introduction of mutations in the surface glycoproteins like the hemagglutinin, allowing escape from antibody-mediated immunity, there is now evidence that influenza viruses can escape in a similar way from CTL-mediated immunity.

Amino Acid Sequence↗
PubMed2004

A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro.

Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in or adjacent to CTL epitopes. Recently, an amino acid substitution (R384G) in an HLA-B*2705-restricted CTL epitope in the influenza A virus nucleoprotein (nucleoprotein containing residues 383 to 391 [NP(383-391)]; SRYWAIRTR, where R is the residue that was mutated) was associated with escape from CTL-mediated immunity. The effect of this mutation on the in vitro influenza A virus-specific CTL response was studied. To this end, two influenza A viruses, one with and one without the NP(383-391) epitope, were constructed by reverse genetics and designated influenza viruses A/NL/94-384R and A/NL/94-384G, respectively. The absence of the HLA-B*2705-restricted CTL epitope in influenza virus A/NL/94-384G was confirmed by using (51)Cr release assays with a T-cell clone specific for the NP(383-391) epitope. In addition, peripheral blood mononuclear cells (PBMC) stimulated with influenza virus A/NL/94-384G failed to recognize HLA-B*2705-positive target cells pulsed with the original NP(383-391) peptide. The proportion of virus-specific CD8+ gamma interferon (IFN-gamma)-positive T cells in in vitro-stimulated PBMC was determined by intracellular IFN-gamma staining after restimulation with virus-infected autologous B-lymphoblastoid cell lines and C1R cell lines expressing only HLA-B*2705. The proportion of virus-specific CD8+ T cells was lower in PBMC stimulated in vitro with influenza virus A/NL/94-384G obtained from several HLA-B*2705-positive donors than in PBMC stimulated with influenza virus A/NL/94-384R. This finding indicated that amino acid variations in CTL epitopes can affect the virus-specific CTL response and that the NP(383-391) epitope is the most important HLA-B*2705-restricted epitope in the nucleoprotein of influenza A viruses.

Animals↗
PubMed2004

Functional compensation of a detrimental amino acid substitution in a cytotoxic-T-lymphocyte epitope of influenza a viruses by comutations.

Influenza A viruses accumulate amino acid substitutions in cytotoxic-T-lymphocyte (CTL) epitopes, allowing these viruses to escape from CTL immunity. The arginine-to-glycine substitution at position 384 of the viral nucleoprotein is associated with escape from CTLs. Introduction of the R384G substitution in the nucleoprotein gene segment of influenza virus A/Hong Kong/2/68 by site-directed mutagenesis was detrimental to viral fitness. Introduction of one of the comutations associated with R384G, E375G, partially restored viral fitness and nucleoprotein functionality. We hypothesized that influenza A viruses need to overcome functional constraints to accumulate mutations in CTL epitopes and escape from CTLs.

Amino Acid Substitution↗
PubMed2004

Influenza vaccination in asthmatic children: effects on quality of life and symptoms.

This study aimed to detect the effect of influenza vaccination on quality of life, symptomatology and spirometry in asthmatic children. A randomised double-blind placebo-controlled trial in 696 (296 in 1999-2000 and 400 in 2000-2001) asthmatic children aged 6-18 yrs, which were vaccinated with either vaccine or placebo, was performed. Children participated for only one influenza season. They recorded symptoms in a diary and reported when symptom scores reached a predefined severity level. If this occurred research nurses visited them twice, first to take a pharyngeal swab and spirometry, and a week later to assess quality of life over the past illness week. Compared with placebo, vaccination improved health-related quality of life in the weeks of illness related to influenza-positive swabs. However, no effect was found for respiratory symptoms recorded in the diaries during those weeks. Similarly, no differences were found for quality of life in all weeks of illness or for respiratory symptoms throughout the seasons. Influenza vaccination was found to have a moderately beneficial effect on quality of life in influenza-positive weeks of illness in children with asthma.

Adolescent↗
PubMed2003

[The 2002/2003 influenza season in the Netherlands and the vaccine composition for the 2003/2004 season].

As in the 2000/2001 and 2001/2002 seasons, the influenza epidemic in the 2002/2003 season started late (week 7 of 2003) and was only moderate in size. Influenza A (H3N2) and B viruses were detected in equal numbers among patients of general practitioners and these two viruses were therefore equally responsible for the epidemic. However, H3N2 viruses dominated isolates taken from hospitals. In haemagglutination-inhibition (HI) assays most of the H3N2 viruses proved highly reactive with antiserum to the vaccine-reference strain A/Moscow/10/99. This was also true for a number of isolates, including those obtained from nursing home residents, closely related to the reference strain A/Finland/170/03. However, an estimated 4% of the H3N2 isolates belonged to the variant A/Fujian/411/02 from China, which constituted the majority of the H3N2 viruses isolated in Europe in the later phase of the season. This variant reacted poorly with antiserum to A/Moscow/10/99. In H1 tests all influenza A(H1N1)-virus isolates and all B-virus isolates were closelyrelated to the corresponding vaccine-reference strains. Taking this data into consideration, the World Health Organization has advised the same vaccine composition for the 2003/2004 season as for the 2002/2003 season, namely: A/Moscow/10/99 (H3N2), A/New Caledonia/20/99 (H1N1) and B/Hong Kong/330/01. There is the possibility of a mismatch occurring between the H3N2-vaccine strain and the circulating H3N2 viruses in the coming influenza season. In March and April 2003 there was an outbreak of influenza-A (H7N7) fowl plague in the Netherlands. A special monitoring survey revealed that 91 people who had handled infected poultry became infected with the H7N7 virus. One of these later died as a result of this. None of the avian and human H7N7-virus isolates examined contained human or porcine influenza-A virus genes.

Global Health↗
PubMed2003

Nosocomial influenza infection among post-influenza-vaccinated patients with severe pulmonary diseases.

OBJECTIVES: To report an outbreak of nosocomial influenza in thirteen out of twenty-two admitted patients suffering from severe lung emphysema. METHODS: Acute-phase and convalescent serum samples of nine patients were collected. An antihaemagglutinin assay was performed to detect a rise in antibodies against influenza A virus. Further information about vaccination history of the patients and healthcare workers was included. RESULTS: The majority of these twenty-two patients was vaccinated with a trivalent vaccine six months earlier. The immunological response showed that the influenza A (H3N2) strain which caused these infections is similar to the vaccine strain A/Sydney/5/97. CONCLUSIONS: The staff of our institute which was not systematically vaccinated may have been the source of infection. The time elapsed between the vaccination and the infection is the probable explanation of this event.

Aged↗