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Claude P Muller

Publications and source records attributed to Claude P Muller.

29 records · Page 2Linked to original sources
PubMed2003

Modelling measles re-emergence as a result of waning of immunity in vaccinated populations.

An age-structured mathematical model of measles transmission in a vaccinated population is used to simulate the shift from a population whose immunity is derived from natural infection to a population whose immunity is vaccine-induced. The model incorporates waning of immunity in a population of vaccinees that eventually will become susceptible to a milder form of vaccine-modified measles with a lower transmission potential than unvaccinated classical measles. Using current estimates of duration of vaccine-derived protection, measles would not be expected to re-emerge quickly in countries with sustained high routine vaccine coverage. However, re-emergence is possible to occur several decades after introduction of high levels of vaccination. Time until re-emergence depends primarily on the contagiousness of vaccine-modified measles cases in comparison to classical measles. Interestingly, in a population with a high proportion of vaccinees, vaccine-modified measles and classical measles would occur essentially in the same age groups. Although waning of humoral immunity in vaccinees is widely observed, re-emergence of measles in highly vaccinated populations depends on parameters for which better estimates are needed.

Adolescent↗
PubMed2003

Neutralising immunogenicity of a polyepitope antigen expressed in a transgenic food plant: a novel antigen to protect against measles.

Transgenic carrot plants were developed expressing a designer polyepitope combining tandem repeats of a protective loop-forming B cell epitope (H386-400) of the measles virus hemagglutinin protein with a human promiscuous, measles-unrelated T cell epitope (tt830-844). Despite the sensitivity of the loop conformation to its molecular environment, proper folding was confirmed by conformation-dependent monoclonal antibodies. The antibodies also reacted with the boiled antigen in Western blot. Immunisation of mice peritoneally with carrot plant extracts induced high titers of antibodies that crossreacted strongly with the virus. Furthermore, the sera neutralised field isolates of different geographic origins and genotypes in a modified plaque reduction neutralisation assay performed on CD150-transfected Vero cells. These results demonstrate that transgenic carrot plants can serve as an efficient expression system to produce highly immunogenic, randomly assembled polyepitope antigens. The combined features of the selected epitopes and the potential of the plant expression system may pave the way towards new vaccines against measles.

Amino Acid Sequence↗
PubMed2003

Limited diversity of measles field isolates after a national immunization day in Burkina Faso: progress from endemic to epidemic transmission?

Despite recent National Immunization Days in Burkina Faso, the rural province of Houët reported >400 measles cases in 2001 (82% not vaccinated). Phylogenetic analysis of 58 measles virus field isolates plus the first sequences from the Democratic Republic of the Congo and the Republic of Congo are reported. All viruses were genotype B3, which is common in the region. In Houët, there were two geographically confined genetic variants, suggesting two independent importation events. Strain diversity in Houët (1.5%) and the Congos was limited in comparison with Ibadan, Nigeria (4.6%), where measles is endemic. Strain variability, assessed by heteroduplex mobility assay, confirmed these findings. Despite large local pools of susceptible persons even after several rounds of vaccination, the limited strain diversity suggests that parts of rural Burkina Faso may be moving from an endemic to an epidemic transmission pattern of measles virus.

Adolescent↗
PubMed2003

The rationale of a peptide-conjugate vaccine against measles.

The live-attenuated measles vaccine is poorly immunogenic in infants because of immune suppressive maternal antibodies and immaturity of the infant's immune system. Selected peptides corresponding to sequential, subdominant B cell epitopes of measles virus (MV) glycoproteins have been shown to induce neutralizing and protective antibodies even in the presence of whole virus antibodies. Similar to polysaccharide-conjugate vaccines, which are highly effective in infants a peptide-conjugate vaccine against measles is proposed. Such a vaccine induces carrier-specific T cells, avoiding measles-specific Th2 cells associated with the risk of atypical measles. This article discusses the rationale of such a strategy and its future potential.

Animals↗
PubMed2003

Immunogenic measles antigens expressed in plants: role as an edible vaccine for adults.

Vaccine-induced immunity against measles is less robust than natural immunity. Waning of immunity in vaccines may eventually require a revaccination of adults. Measles antigens expressed in plants have been shown to be antigenic and immunogenic both after invasive and oral vaccination. Strategies for the vaccination of adults, the potential of an oral measles vaccine produced in edible plants and the design of suitable antigens are discussed.

Administration, Oral↗
PubMed2003

Experimental vaccines against measles in a world of changing epidemiology.

Vaccination with the current live attenuated measles vaccine is one of the most successful and cost-effective medical interventions. However, as a result of persisting maternal antibodies and immaturity of the infant immune system, this vaccine is poorly immunogenic in children <9 months old. Immunity against the live vaccine is less robust than natural immunity and protection less durable. There may also be some concern about (vaccine) virus spread during the final stage of an eventual measles eradication program. Opinions may differ with respect to the potential threat that some of these concerns may be to the World Health Organisation goal of measles elimination, but there is a consensus that the development of new measles vaccines cannot wait. Candidate vaccines are based on viral or bacterial vectors expressing recombinant viral proteins, naked DNA, immune stimulating complexes or synthetic peptides mimicking neutralising epitopes. While some of these candidate vaccines have proven their efficacy in monkey studies, aerosol formulated live attenuated measles vaccine are evaluated in clinical trials.

Animals↗
PubMed2003

Functional fine-mapping and molecular modeling of a conserved loop epitope of the measles virus hemagglutinin protein.

Neutralizing and protective monoclonal antibodies (mAbs) were used to fine-map the highly conserved hemagglutinin noose epitope (H379-410, HNE) of the measles virus. Short peptides mimicking this epitope were previously shown to induce virus-neutralizing antibodies [El Kasmi et al. (2000) J. Gen. Virol.81, 729-735]. The epitope contains three cysteine residues, two of which (Cys386 and Cys394) form a disulfide bridge critical for antibody binding. Substitution and truncation analogues revealed four residues critical for binding (Lys387, Gly388, Gln391 and Glu395) and suggested the binding motif X7C[KR]GX[AINQ]QX2CEX5 for three distinct protective mAbs. This motif was found in more than 90% of the wild-type viruses. An independent molecular model of the core epitope predicted an amphiphilic loop displaying a remarkably stable and rigid loop conformation. The three hydrophilic contact residues Lys387, Gln391 and Glu395 pointed on the virus towards the solvent-exposed side of the planar loop and the permissive hydrophobic residues Ile390, Ala392 and Leu393 towards the solvent-hidden side of the loop, precluding antibody binding. The high affinity (Kd = 7.60 nm) of the mAb BH216 for the peptide suggests a high structural resemblance of the peptide with the natural epitope and indicates that most interactions with the protein are also contributed by the peptide. Improved peptides designed on the basis of these findings induced sera that crossreacted with the native measles virus hemagglutinin protein, providing important information about a lead structure for the design of more stable antigens of a synthetic or recombinant subunit vaccine.

Amino Acid Motifs↗
PubMed2002

Neutralizing B cell response in measles.

Co-evolving mechanisms of immune clearance and of immune suppression are among the hallmarks of measles. B cells are major targets cells of measles virus (MV) infection. Virus interactions with B cells result both in immune suppression and a vigorous antibody response. Although antibodies fully protect against (re)infection, their importance during the disease and in the presence of a potent cellular response is less well understood. Specific serum IgM appears with onset of rash and confirms clinical diagnosis. After isotype switching, IgG1 develops and confers life-long protection. The most abundant antibodies are specific for the nucleoprotein, but neutralizing and protective antibodies are solely directed against the two surface glycoproteins, the hemagglutinin and the fusion protein. Major neutralizing epitopes have been mapped mainly on the hemagglutinin protein with monoclonal antibodies, producing an increasingly comprehensive map of functional domains.

Animals↗
PubMed2002

Identification of a second major site for CD46 binding in the hemagglutinin protein from a laboratory strain of measles virus (MV): potential consequences for wild-type MV infection.

Natural or wild-type (wt) measles virus (MV) infection in vivo which is restricted to humans and certain monkeys represents an enigma in terms of receptor usage. Although wt MV is known to use the protein SLAM (CD150) as a cell receptor, many human tissues, including respiratory epithelium in which the infection initiates, are SLAM negative. These tissues are CD46 positive, but wt MV strains, unlike vaccinal and laboratory MV strains, are not thought to use CD46 as a receptor. We have identified a novel CD46 binding site at residues S548 and F549, in the hemagglutinin (H) protein from a laboratory MV strain, which is also present in wt H proteins. Our results suggest that although wt MV interacts with SLAM with high affinity, it also possesses the capacity to interact with CD46 with low affinity.

Antigens, CD↗
PubMed2002

Prevalence of antibodies against canine distemper virus among red foxes in Luxembourg.

Canine distemper virus (CDV) has a wide host spectrum, and during the past years, distemper has been observed in species that were previously not considered to be susceptible. In this study, we investigated the prevalence of CDV-specific antibodies in red foxes (Vulpes vulpes) sampled between May and November 1997. About 9 to 13% of the Luxembourg red fox population is positive for antibodies against CDV. Thus a sizeable proportion of red foxes has been exposed to CDV in the wild. The significance of CDV in red foxes is discussed.

Animals↗