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Biomedical subjects

A Osterhaus

Publications and source records attributed to A Osterhaus.

At least 19 recordsLinked to original sources
PubMed2005

A new European perspective of influenza pandemic planning with a particular focus on the role of mammalian cell culture vaccines.

Sixteen EU scientists and doctors were interviewed about pandemic planning using psychometric methods applied to a scientific problem for the first time. Criticism was aimed at countries which have no plan whatsoever, the majority of nations. Many such countries have not invested in scientific infrastructure and public health. Amongst the 15 or so published pandemic plans a lack of detail was identified. Of particular need was investment into avian virus vaccine stocks (H1-15), prepared licenses of vaccine and pre purchase and agreed distribution, investment into stocks of antivirals, antibiotics and masks. Most but not all members of the group predicted a global outbreak within 5 years, most probably starting in SE Asia. However it was recognised that a pandemic could start anywhere in the world which had juxtaposition of young people, chickens, ducks and pigs. Mammalian cell culture production using wild type virus with the production factory at category III levels of security was exemplified. Antivirals would be essential to ameliorate the first wave of infection although significant quantities of cell grown vaccine could be produced if, as in 1918, 1957 and 1968 there is a long period between the first virus isolation and person to person spread. The wider scientific community is more energised than previously for very serious preparations to be in place way before the outbreak begins as this is a major public health problem, completely dwarfing concerns about bioterrorism.

Animals↗
PubMed2003

Efficacy of ivermectin and moxidectin against Otostrongylus circumlitus and Parafilaroides gymnurus in harbour seals (Phoca vitulina).

Verminous bronchopneumonia caused by infection with Otostrongylus circumlitus and Parafilaroides gymnurus is an important cause of death during the rehabilitation of harbour seals (Phoca vitulina). During the winter of 2000/01, 35 juvenile harbour seals with severe clinical signs of verminous bronchopneumonia were treated with either 0.2 mg/kg ivermectin orally or 0.2 mg/kg moxidectin subcutaneously, and monitored for 30 days. The efficacy of the anthelmintics was determined by the pattern of larval excretion (Baermannisation) and the progress of the clinical signs. Both anthelmintics had reduced larval excretion by at least 99 per cent after 10 days, but the seals' rapid breathing rate and and dyspnoea returned to normal more quickly in the animals treated with moxidectin. The pharmacokinetics of the anthelmintics were determined by solid-phase extraction, and high-performance liquid chromatography with fluorescence detection. Moxidectin had a mean (sd) residence time of 9.04 (2.12) days compared with 4.83 (1.14) days for ivermectin.

Animals↗
PubMed2001

Catastrophes after crossing species barriers.

Probably the most tragic examples of virus infections that have caused the deaths of many millions of people in the past century were the influenza and AIDS pandemics. These events occurred as a direct result of the introduction of animal viruses into the human population. Similarly, mass mortalities among aquatic and terrestrial mammals were caused by the introduction of viruses into species in which they had not previously been present. It seems paradoxical that at a time when we have managed to control or even eradicate major human virus infections like polio and smallpox we are increasingly confronted with new or newly emerging virus infections of humans and animals. A complex mix of social, technological and ecological changes, and the ability of certain viruses to adapt rapidly to a changing environment, seems to be at the basis of this phenomenon. Extensive diagnostic and surveillance networks, as well as novel vaccine- and antiviral development strategies should provide us with the safeguards to limit its impact.

Animal Diseases↗
PubMed2001

Zanamivir: a rational approach to influenza B.

Influenza B viruses have co-circulated with the HIN1 and H3N2 subtypes of influenza A since 1977. Influenza A viruses are found in various animals, whereas influenza B viruses are probably restricted to humans. The lack of an animal reservoir means that the virus has no potential for genetic reassortment across species. In addition, influenza B viruses are more serologically homogeneous than influenza A viruses. Thus, the chance of influenza B causing a pandemic is much lower than that of influenza A. However, influenza B viruses are still a frequent cause of local disease outbreaks and epidemics as a result of antigenic drift. Any prophylactic or therapeutic measure must, therefore, be effective against both influenza A and B viruses. Zanamivir is the first widely approved neuraminidase inhibitor for the treatment of influenza. It is delivered directly to the primary site of viral replication, the respiratory tract, and is well tolerated and effective in the treatment of both influenza A and B. Data in prophylaxis are also encouraging. Zanamivir is the only drug proven to be clinically effective against both influenza A and B virus infections.

Animals↗
PubMed2000

Transgenic mice expressing human HLA and CD8 molecules generate HLA-restricted measles virus cytotoxic T lymphocytes of the same specificity as humans with natural measles virus infection.

Control of primary measles virus (MV) infection in humans and continued maintenance of immune memory that protects against reinfection are mediated primarily through the anti-MV T cell response, as judged by observations of children with defects in antibody formation but competency in making T cells. Further, the failure of T cell responses in those infected with MV most often leads to overwhelming infection. To better define and manipulate the elements involved in human T cell responses to MV, we analyzed the generation of HLA-restricted cytotoxic T lymphocytes (CTL) in a small animal model. Transgenic mice expressing the human class I MHC antigen HLA-B27 in conjunction with human CD8 molecules produced vigorous HLA-restricted CTL responses to MV antigens, paralleling those in MV infection of humans. In addition, such humanized mice generated human CD8 coreceptor-dependent HLA-B27-restricted CTL with the same specificity for recognition of MV fusion (F) peptide RRYPDAVYL as reported for humans during natural MV infection. Neither murine beta(2)-microglobulin nor murine CD8 substituted adequately as coreceptors for the HLA-B27 heavy chain. By contrast, HLA-A2.1-restricted responses to measles could be generated in the absence of expression of human beta(2)-microglobulin or CD8(+) molecules in HLA-A2.1/K(b) transgenic mice. Thus a small animal model is now available for studying strategies for optimizing human CD8(+) T cell responses and for testing vaccines. This model offers the potential, when combined with the newly reported CD46 transgenic mouse model in which MV replicates in cells of the immune system, for uncoding the molecular mechanism of MV-induced immunosuppression.

Animals↗
PubMed2000

[Circulation of virus and interspecies contamination in wild animals].

Paradoxically, just when we have succeeded in eradicating and/or bringing under control the major viral infections (smallpox, poliomyelitis, measles) numerous viral infections are emerging in man and in animals. Changes in our social environment, technological and ecological equilibrium have facilitated this phenomenon. Furthermore, certain of these viruses have demonstrated an almost unlimited capacity to adapt genetically to environmental change. HIV has already infected 40 million individuals, but monkeypox, Ebola, simian herpes can cause epidemics with serious if not fatal outcomes. Haemorrhagic fever epidemics have resulted from human contact with Flavivirus infected rodents and insects. Paramyxoviruses and morbiliviruses can cause fatal outcomes in man and animals. And the three influenza epidemics having occurred in the 20th century all came from the type A avian reservoir. The often complex combinations of predisposing factors having facilitated the emergence of several epidemics merit further consideration.

Animals↗
PubMed1999

Integration of vitamin A supplementation with the expanded program on immunization does not affect seroconversion to oral poliovirus vaccine in infants.

Childhood immunization programs may provide infrastructure for delivering vitamin A supplements to infants in developing countries. The effect of giving vitamin A, an immune enhancer, on antibody responses to trivalent oral poliovirus vaccine (TOPV) is unknown. A randomized, double-blind, placebo-controlled clinical trial was conducted to determine the effect of giving vitamin A simultaneously with TOPV on antibody responses to poliovirus. Infants (n = 467) received oral vitamin A, 15 mg retinol equivalent (RE), 7.5 mg RE or placebo with TOPV at 6, 10 and 14 wk of age. Antibody responses to poliovirus types 1, 2 and 3 were measured by a microvirus neutralization assay at enrollment and at 9 mo of age. Seroconversion rates to poliovirus types 1, 2 and 3 ranged from 98 to 100% in the three treatment groups, and there were no differences in mean antibody titers to poliovirus types 1, 2 and 3 among treatment groups. This study demonstrates that oral vitamin A does not affect antibody responses to poliovirus vaccine when integrated with the Expanded Program on Immunization.

Adult↗
PubMed1999

In vivo activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee.

A 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks after infusion. HBsAg and antibodies against HBsAg (anti-HBs) were quantified by radioimmunoassay and enzyme immunoassay. Free anti-HBs was never detected. Thirty min after the start of the infusion the HBsAg level was minimal with maximum loading of the chimpanzee HBsAg with human immunoglobulin. HBsAg complexes could be dissociated by acid treatment. The HBsAg level was completely restored on day 7. Similar results were obtained for the preS1-containing particles that may represent the infectious viral particles in the chimpanzee serum. A mouse monoclonal anti-HBs (HBs.OT40) was found to compete with 9H9 in artificial immune complexes with the pre-treatment HBsAg from the chimpanzee. Used as a conjugate, HBs.OT40 yielded a maximum decrease in the signal in the 30 min sample compared to non-competing anti-HBs conjugates. This indicates binding of HBsAg with 9H9 in the circulation of the chimpanzee. Immune-complexed 4-7B could not be detected by its corresponding 4-7B peptide conjugate, probably due to its low concentration in the complexes. It is concluded that human monoclonal anti-HBs can effectively reduce the level of HBsAg in serum from this chronic carrier. Monoclonals 9H9 and 4-7B may complement each other due to their different mechanisms of inactivation, probably with higher efficiency than that monitored by our HBsAg screening assays.

Animals↗
PubMed1997

A subtype-specific peptide-based enzyme immunoassay for detection of antibodies to the G protein of human respiratory syncytial virus is more sensitive than routine serological tests.

Peptides deduced from the central conserved region (residues 158 to 189) of protein G of human respiratory syncytial virus (HRSV) subtypes A and B were used as antigens in subtype-specific enzyme-linked immunosorbent assays (G-peptide ELISAs). These G-peptide ELISAs were compared with seven other serological assays to detect HRSV infection: ELISAs based on complete protein G, on fusion protein F, and on nucleoprotein N; a complement fixation assay; a virus neutralization test; and ELISAs for the detection of immunoglobulin A (IgA) or IgM antibodies specific for HRSV. In paired serum samples from patients with HRSV infection, more infections were diagnosed by the G-peptide ELISA (67%) than by all other serological tests combined (48%). Furthermore, for 16 of 18 patients (89%), the G-peptide ELISAs were able to differentiate between antibodies against HRSV subtypes A and B. This study shows that peptides corresponding to the central conserved region of the attachment protein G of HRSV can successfully be used as antigens in immunoassays. The G-peptide ELISA appeared to be more sensitive than conventional tests for the detection of HRSV antibody titer rises.

Amino Acid Sequence↗
PubMed1996

Contaminant-induced immunotoxicity in harbour seals: wildlife at risk?

Persistent, lipophilic polyhalogenated aromatic hydrocarbons (PHAHs) accumulate readily in the aquatic food chain and are found in high concentrations in seals and other marine mammals. Recent mass mortalities among several marine mammal populations have been attributed to infection by morbilliviruses, but a contributing role for immunotoxic PHAHs, including the polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) was not ruled out. We addressed this issue by carrying out a semi-field study in which captive harbour seals were fed herring from either the relatively uncontaminated Atlantic Ocean or the contaminated Baltic Sea for 2 years. We present here an overview of results obtained during this study. An impairment of natural killer (NK) cell activity, in vitro T-lymphocyte function, antigen-specific in vitro lymphocyte proliferative responses, and in vivo delayed-type hypersensitivity and antibody responses to ovalbumin was observed in the seals fed the contaminated Baltic herring. Additional feeding studies in PVG rats using the same herring batches suggested that an effect at the level of the thymus may be responsible for changes in cellular immunity, that virus-specific immune responses may be impaired, and that perinatal exposure to environmental contaminants represents a greater immunotoxic threat than exposure as a juvenile or adult. Together with the pattern of TCDD toxic equivalents of different PHAHs in the herring, these data indicate that present levels of PCBs in the aquatic food chain are immunotoxic to mammals. A review of contaminant levels in free-ranging harbour seals inhabiting polluted areas of Europe and North America suggests that many populations may be at risk to immunotoxicity. This could result in diminished host resistance and an increased incidence and severity of infectious disease.

Animals↗
PubMed1996

Development and evaluation of alternative testing methods for the in vivo NIH potency test used for the quality control of inactivated rabies vaccines.

The potency control of rabies vaccines is routinely performed in a vaccination-challenge test (NIH test), which induces substantial distress and suffering in laboratory mice. Although, according to the recommendations by the WHO, partial replacement of this in vivo potency test by in vitro antigenicity testing is permitted, no internationally accepted alternative testing method is yet available. In the present study, we focussed on the use of monoclonal antibody-based ELISA systems for the quantitative detection of rabies glycoprotein in vaccines for human and veterinary use. Results in the newly developed competitive binding ELISA for glycoprotein quantification showed good correlation with NIH potencies. Also, the applicability for vaccines based on different virus strains was demonstrated. Quantification methods were remodelled to convenient ELISA kits for interlaboratory evaluation of the sensitivity and reproducibility in an internal collaborative study. The relevance of the data generated with these assays is currently assessed by parallel studies evaluating vaccine-induced B and T cell-mediated immunity. We speculate that the assays developed will provide, at least in part, a suitable replacement for the NIH potency test.

Animal Testing Alternatives↗
PubMed1995

Epidemiology and laboratory diagnosis of hantavirus (HTV) infections.

Hantavirus (HTV) is recently discovered "hemorrhagic fever virus" belonging to the Bunyaviridae family, which is spread throughout the world by wild rodents and/or laboratory rats. During an epidemic in the Belgian-French Ardennes in 1993, more than 200 acute cases were recorded of the milder European form of HTV-illness, otherwise known as Nephropathia epidemica (NE). This variant may be recognized by the sudden onset of fever, acute renal failure, thrombocytopenia and sometimes by ophthalmologic complications. The symptomatology is rather aspecific and diagnosis can only be confirmed by serologic tests, of which the best option nowadays seems to be: screening by IgG EIA, followed by IgM confirmation with a mu-capture EIA test. Some of the tests described allow an evaluation of the causative serotype or even the moment of infection. Next to the "classic" serologic assays for detection of specific viral antibodies, we describe briefly our own experience with newer tests such as "high density particle agglutination" and "line immuno assay". Polymerase chain reaction for viral RNA genome typing and immunohistochemical colouring of the viral antigen in tissues seem to offer promising alternatives for the immediate future.

Belgium↗
PubMed1994

Enzyme immunoassay (ELISA) for the evaluation of antibodies directed to the CD4 receptor-binding site of the HIV gp120 molecule.

The interaction between the HIV envelope glycoprotein gp120 and the CD4 molecule is probably the most important primary event determining HIV infection. Reactivity with the native viral envelope has been difficult to measure due to the lack of gp120 ligand purified directly from primary virus cultures. We have developed an ELISA, utilizing Galanthus nivalis agglutinin (GNA) which selectively binds native HIV envelope gp120 in culture medium. The GNA-based ELISA eliminates the need for isotope-labelled reagents, live cells and recombinant non-natively glycosylated envelope proteins and offers an easy way of using gp120 directly from crude HIV culture medium. The reactivities of sera from several categories of HIV infected individuals were assayed for inhibition of the HIV-1 gp120-CD4 binding. 19/32 (59.3%) sera from asymptomatic individuals and 7/10 (70%) sera from ARC/AIDS patients blocked the CD4-gp120 binding. 20 serum samples from uninfected individuals showed a gp120-CD4 interaction blocking capacity of 0-15%. Two monoclonal antibodies, T4.2 directed to CD4 and 1171 directed to the CD4 binding site of gp120 were used as positive controls. Both Mabs inhibited CD4-gp120 binding by 66-90%.

Adolescent↗
PubMed1994

Major histocompatibility complex class I-associated vaccine protection from simian immunodeficiency virus-infected peripheral blood cells.

To evaluate the effectiveness of vaccine protection from infected cells from another individual of the same species, vaccinated rhesus macaques (Macaca mulatta) were challenged with peripheral blood mononuclear cells from another animal diagnosed with acquired immune deficiency syndrome (AIDS). Half of the simian immunodeficiency virus (SIV)-vaccinated animals challenged were protected, whereas unprotected vaccinates progressed as rapidly to AIDS. Protection was unrelated to either total antibody titers to human cells, used in the production of the vaccine, to HLA antibodies or to virus neutralizing activity. However, analysis of the serotype of each animal revealed that all animals protected against cell-associated virus challenge were those which were SIV vaccinated and which shared a particular major histocompatibility complex (MHC) class I allele (Mamu-A26) with the donor of the infected cells. Cytotoxic T lymphocytes (CTL) specific for SIV envelope protein were detected in three of four protected animals vs. one of four unprotected animals, suggesting a possible role of MHC class I-restricted CTL in protection from infected blood cells. These findings have possible implications for the design of vaccines for intracellular pathogens such as human immunodeficiency virus (HIV).

Amino Acid Sequence↗