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C Blondeau

Publications and source records attributed to C Blondeau.

At least 19 recordsLinked to original sources

IgG subclass distribution in serum and various mucosal fluids of HIV type 1-infected subjects.

We measured total IgG1, IgG2, IgG3, and IgG4 concentrations by ELISA in serum (S), total saliva (TS), cervicovaginal secretions (CVS), seminal secretions (SPE), and rectal secretions (RS) from either CDC II/III HIV-1-infected subjects or healthy volunteers. Human serum albumin was measured in parallel to calculate the relative coefficient of excretion (RCE). Levels of IgG1 and IgG3 directed against gp120 MN also were measured by ELISA in all samples, and the specific activity (SA) calculated. HIV-1-specific IgG2 and IgG4 were not compared, as total IgG2 and total IgG4 levels in HIV-1-infected subjects were found to be lower than in the healthy controls. Despite substantial interindividual variability, total IgG1 and IgG3 concentrations in all fluids were greater in the HIV-1-infected subjects than in the healthy controls. Calculations of RCE indicated predominantly a transudative origin for IgG subclasses in the different mucosal fluids, except for CVS, in which IgG1, IgG2, and IgG4 was produced locally. The transduction behavior of IgG3 in secretions appears to be different from that of other IgG subclasses. HIV-1-infected subjects were considered positive for IgG1 and IgG3 antibodies against gp120 MN if their antibody levels exceeded the maximum titer measured in the control group. Positive levels of anti-gp120 MN IgG1 were detected for 100% of HIV-1-infected individuals in S, CVS, and SPE, 97% in TS, and 75% in RS. Fewer subjects had positive levels of IgG3 to gp120 MN in their secretions (maximum 67% in CVS). Despite the low concentrations of total IgG3, mean SA values for IgG3 to gp120 MN were greater in secretions than in serum. No significant difference in the SA values for IgG1 to gp120 MN was observed between the different fluids. Only CVS had a local production of HIV-specific IgG1 Our results highlight the importance of an HIV-specific IgG1 and IgG3 immune response in mucosal fluids from HIV-1-infected subjects.

Adult↗

Identification of linear viscoelastic constitutive models.

Accelerations induce in the brain mechanical stresses that may explain the loss of consciousness feared by fighter pilots. In this study, the brain is modelled as a multi-domain structure and a finite element method is used to identify the constitutive law parameters of each domain and then to analyse the stress level in the brain. The loading and observed strain rates induced by hypergravity seem to indicate a quasi-static behaviour of the brain structure. A general procedure has been developed to characterise the behaviour of a structure including several domains. Each of them is assumed to be isotropic and homogeneous with a linear viscoelastic behaviour. These constitutive laws were identified using only the displacements of several nodes on the envelope discarding the displacements between domains at the interaction surfaces. These interfaces may be buried inside the structure and not connected with the external surface. Two validation examples are proposed to show the reliability and effectiveness of the method.

Acceleration↗

[Photosensitive epilepsy and television epilepsy].

Photosensitivity is defined by the appearance of occipital or more diffuse electroencephalographic spikes and waves induced by intermittent light stimulation (ILS), particular patterns, TV-watching, and video games. Photosensitivity is a genetic characteristic. Only the diffuse spikes and waves induced by ILS are correlated with epilepsy. Pure photogenic epilepsy is characterized by seizures which are only visually induced, usually by watching TV. Video games sometimes add a trigger effect due to slowly moving patterns or intense brightness. Several epileptic syndromes are associated with a photosensitivity with or without visually-induced seizures, mainly generalized idiopathic epilepsy.

Adolescent↗

An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study.

Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical technique is uniformly accepted and used in vaccine evaluation studies to determine the acceptable level of agreement between a laboratory result and the assigned value for a given serum sample. This multicenter study describes the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-control sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) developed for this study. After provisional or trial antibody concentrations were assigned to the quality-control serum samples for this study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error between assigned values and laboratory-determined concentrations proved to be the most informative of the four methods. We present guidelines that a laboratory may follow to analyze a series of quality-control sera to determine if it can reproduce the assigned antibody concentrations within an acceptable level of tolerance. While this study focused on a pneumococcal IgG ELISA, the methods that we describe are easily generalizable to other immunological assays.

Antibodies, Bacterial↗

Comparison of the distribution of IgG and IgA antibodies in serum and various mucosal fluids of HIV type 1-infected subjects.

We compared IgG and IgA distribution in serum, three different salivary samples, two different rectal secretion samples, cervicovaginal secretions, and seminal secretions from asymptomatic CDC stage II/III HIV-1-infected subjects (n = 44) and from HIV-1-seronegative volunteers (n = 52). In-house ELISAs were used to measure total IgG and total IgA levels, as well as HIV-specific anti-gp120 MN and anti-p24 LAI IgG and IgA. Human serum albumin was titrated in parallel to calculate the relative coefficient of excretion (RCE). In spite of substantial interindividual variability, total IgG concentrations in all fluids were found to be significantly greater in the HIV-1-infected group than in the seronegative subjects. Calculation of RCE values revealed three different types of mucosal secretion: secretions with no local Ig production, such as sperm; secretions with local production of IgA and transudative origin of IgG, such as salivary and rectal samples; and secretions with local production of both IgG and IgA, such as in cervicovaginal secretions. For all mucosal specimens from HIV-1-infected subjects, the response to HIV-1 was predominantly IgG, with highest titers observed in cervicovaginal secretions (although these were lower than serum levels). In contrast, the specific IgA response appeared weaker in the mucosa than in serum.

Adult↗

Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L'Agence Nationale de Recherches sur Le Sida.

A live recombinant canarypox vector expressing HIV-1 gpl20 MN tm/gag/protease LAI (ALVAC-HIV, vCP205) alone or boosted by a p24E-V3 MN synthetic peptide (CLTB-36) was tested in healthy volunteers at low risk for HIV infection for their safety and immunogenicity. Both antigens were well tolerated. ALVAC-HIV (vCP205) induced low levels of neutralizing antibodies against HIV-1 MN in 33% of the volunteers. None of them had detectable neutralizing antibodies against a nonsyncytium-inducing HIV-1 clade B primary isolate (Bx08). After the fourth injection of vCP205, CTL activity was detected in 33% of the volunteers and was directed against Env, Gag, and Pol. This activity was mediated by both CD4+ and CD8+ lymphocytes. On the other hand, the CLTB-36 peptide was poorly immunogenic and induced no neutralizing antibodies or CTLs. Although the ALVAC-HIV (vCP205) and CLTB-36 prime-boost regimen was not optimal, further studies with ALVAC-HIV (vCP205) are warranted because of its clear induction of a cellular immune response and utility as a priming agent for other subunit antigens such as envelope glycoproteins, pseudoparticles, or new peptides.

AIDS Vaccines↗

New acellular pertussis-containing paediatric combined vaccines.

Combined pediatric vaccines have the advantages of conferring protection against multiple common infectious diseases with a reduced number of injections. Their use should lead to better compliance to recommended vaccination schedules. Diphtheria (D), tetanus (T) and whole-cell pertussis vaccine (P) have been successfully combined, with or without inactivated poliovirus vaccine (IPV) in the same syringe for many years. Recently developed acellular pertussis (aP) Haemophilus influenzae type B (Hib), inactivated poliomyelitis virus and hepatitis B vaccines are ideal candidates for inclusion in current combined vaccines. Nevertheless, the development of new combinations has to face preclinical and clinical issues: the appropriate formulation of the new antigen(s) and other vaccine components needs to be determined to ensure compatibility and guard against potential additive or unexpected adverse reactions; potential immunological interference between antigens and the negative impact of other vaccine components on immunogenicity may occur, and these have to be examined also. Whole-cell pertussis vaccines are highly protective against whooping cough, but the severe adverse reactions that these vaccines sometimes produce have led to hesitation over their use, including the decision of some countries to stop pertussis immunization. To increase the acceptability of pertussis vaccination, Pasteur Mérieux Connaught has developed a combined D, T and a two-component acellular pertussis vaccine (DTaP), composed of purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA), which has been shown to be effective in an efficacy trial conducted in Senegal. Acellular DTaP vaccines are immunogenic and have a better safety profile than DTP vaccines, when given either for the primary series, for the booster vaccination or for both. In order to meet worldwide demands, the combined DTaP-IPV or DTP-IPV has been developed for countries where IPV is recommended. Following the encouragement of the WHO, an H. influenzae type B tetanus-conjugated (Act-HIB) vaccine, has been combined in a full liquid formulation with the whole-cell DTP. This vaccine showed a good safety and immunogenicity profile in infants and in toddlers. A combined DTaP-IPV-PRP-T vaccine (where the Act-HIB vaccine is reconstituted by the full-liquid DTaP-IPV) also has been successfully developed both for the primary series and for booster vaccination; although, a reduced immunogenicity against PRP observed after the primary series, this did not affect vaccine priming. Hepatitis B immunization campaigns targeting high-risk groups have failed to control the disease in areas of low endemicity. In 1992, the WHO recommended that hepatitis B vaccination should be integrated into the EPI in all countries by 1997-1999. For that purpose, hepatitis B vaccine is currently evaluated in pediatric combined vaccines. Developing new combination vaccines is a difficult but essential process for maintaining high immunization rates worldwide against infectious diseases, provided that the costs are acceptable. New combined vaccines including pneumococcal and meningococcal component are under wide-scale development.

Hepatitis B Vaccines↗

Development and standardization of methods to evaluate the antibody response to an HIV-1 candidate vaccine in secretions and sera of seronegative vaccine recipients.

Enzyme-linked immunosorbent assays (ELISA) were developed to test, in serum and mucosal samples, total IgG, total IgA, serum albumin, and anti-gp120 MN and anti-p24 LAI IgG and IgA levels. These ELISAs were optimized according to reagents and experimental conditions. Inter- and intra-assay coefficients of variation ranged from 3.3% to 18.6%. The ELISA results were linear and precise, and for anti-HIV-1 IgG and IgA, the analytical recovery was close to 100%. For IgG and IgA titration against gp120 MN and p24 LAI, standards were made using pooled sera or gammaglobulins with assigned titres in ELISA units per ml (EU/ml). These standards were used to obtain a linear regression curve that could then be used to obtain the titres of experimental samples. The cut-offs for positivity were determined for sera and mucosal fluid using healthy controls. Validation conditions were defined for ELISAs, and samples that did not satisfy these conditions were retested. Measurement of total IgG and IgA allowed normalization and comparison of the results of specific immunoglobulin levels between different samples. Serum albumin was tested as a marker of transudation from serum to mucosal fluid, allowing calculation of the relative coefficient of excretion, which is one element required to determine the origin of the immunoglobulin detected in mucosal samples. These ELISAs were developed with samples from HIV-1-infected and healthy subjects. We now have the tools to study and understand mucosal immunity in seronegative subjects vaccinated with an HIV-1 candidate vaccine.

AIDS Vaccines↗

Persistence of antibodies to the Salmonella typhi Vi capsular polysaccharide vaccine in South African school children ten years after immunization.

Between 10 and 11 years after children were vaccinated with Vi capsular polysaccharide of Salmonella typhi or meningococcal A + C control vaccine in a double blind randomized trial, we traced 83 subjects, aged 16-20 years. A blood sample was taken for determination of Vi antibody titres in both groups by radioimmunoassay. TO and TH titres were also done to assess if the participants had had recent exposure to typhoid fever. Fifty-eight percent of subjects in both groups had protective levels of Vi antibody against Salmonella typhi (a titre greater than 1 microgram ml-1). There was no significant difference in the levels of Vi antibodies in the cases versus the controls (p = 0.5). Two of the children who had received meningococcal A + C vaccine had recently had typhoid fever. Our data show that adolescents in typhoid endemic areas have high levels of Vi antibodies regardless of previous vaccination status, suggesting that Vi antibodies are acquired in adolescence by a large percentage of the population in this area. Moreover, Vi vaccination has led to ongoing antibody production in greater than 50% of Vi vaccinated children in an endemic area for a period of 10 years. Ongoing antigenic exposure may have contributed to these antibody levels.

Adolescent↗

Comparison of the immunogenicity and safety of two 17D yellow fever vaccines.

As part of the clinical validation process of a new working seed of a licensed yellow fever vaccine (new working seed PV26, Stamaril; Pasteur Mérieux Connaught, Lyon, France), the immunogenicity and safety of two batches of this vaccine (PM-YF) were compared with those of another commercially available vaccine (Arilvax; Evans Medical-Wellcome, Liverpool, United Kingdom) in 211 healthy adults. While the geometric mean titer values at days 10-14 and day 28 after vaccination were higher in the PM-YF group, the vaccines provided equivalent seroprotection (titers > or = 1/10) one month after a single vaccine dose (100% PM-YF versus 99% W-YF; P = 0.001, by one-sided equivalence test). Both vaccines were safe. There were no serious local or systemic reactions reported, nor any clinically significant hepatic function abnormalities associated with the use of either vaccine. These two 17D yellow fever vaccines from different European vaccine manufacturers were highly immunogenic and safe, and provided equivalent seroprotection.

Adolescent↗

Antibody persistence following preexposure regimens of cell-culture rabies vaccines: 10-year follow-up and proposal for a new booster policy.

Subjects (n = 312) received either the human diploid cell rabies vaccine (HDCV) or the purified Vero cell rabies vaccine (PVRV) according to either two-injection (days 0 and 28) or three-injection (days 0, 7, and 28) primary regimens. They received a booster injection at 1 year. Rabies antibody levels were measured after the primary series and the booster and then each year for the next 10 years. The results confirm the superior long-term immunogenicity of the three-injection over the two-injection protocol. HDCV and PVRV in three doses were equally immunogenic. A booster injection at 1 year provides long-term seroconversion (titer > or = 0.5 IU/mL). Antibody titers 2 weeks after the 1-year booster allowed prediction of long-term immunity. Good responders, with titers > or = 30 IU/mL, were protected for at least 10 years. An algorithm for differentiation between good responders and poor responders with respect to vaccine booster strategies is proposed.

Adolescent↗

Clinical acceptability and immunogenicity of a pentavalent parenteral combination vaccine containing diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b conjugate antigens in two-, four- and six-month-old Chilean infants.

BACKGROUND: In recent years additional parenteral vaccines have been recommended for routine immunization of infants in the US and elsewhere. The ability to administer multiple vaccines as a single injection without unacceptably increasing reactogenicity or decreasing immunogenicity of any component would offer many practical advantages. METHODS: A randomized, open, controlled trial was conducted to assess the tolerance profile and immunogenicity, as well as to identify potential antigenic interferences, resulting from administration of a parenteral combination vaccine for infants. The vaccine contains diphtheria and tetanus toxoids, acellular pertussis antigens (DTaP), enhanced inactivated poliovirus (eIPV) and Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T). Infants (n=711) were randomly assigned to receive 1 of 5 regimens as the primary series at 2, 4 and 6 months of age, by group: (1) DTaP plus oral polio vaccine (OPV); (2) DTaP plus eIPV (separate injections); (3) DTaP-eIPV combined as a single injection; (4) DTaP-eIPV combined, plus a separate injection of PRP-T; or (5) DTaP-eIPV combined and reconstituting PRP-T, as a single injection. At 3, 5 and 7 months Groups 1, 2 and 3 received PRP-T. At 12 months all infants received a booster dose of DTaP reconstituting PRP-T as a single injection, plus a separate injection of measles, mumps and rubella vaccine. Groups 2, 3, 4 and 5 received OPV at 7 months, and all infants received OPV at 13 months. Serum immune responses were measured to the primary series at 2 and 7 months and to the booster dose at 12 and 13 months. RESULTS: Reaction rates were similar among groups. In the primary series combining eIPV with DTaP decreased geometric mean titers (GMTs) to diphtheria, tetanus and pertussis. In addition concomitant PRP-T (either simultaneous or combined) with DTaP-eIPV lowered anti-PRP and further decreased tetanus GMTs. Nonetheless in 100% of infants protective titers were achieved against diphtheria and tetanus (>0.01 IU/ml each) and against the poliovirus types 1, 2 and 3 after eIPV (Groups 2 to 5); 99% of infants (Groups 4 and 5) had protective titers against PRP (> or = 0.15 microg/ml). After boosting with DTaP/PRP-T decreased GMTs to diphtheria and PRP antigens were observed in the groups that received DTaP and eIPV combined. Nonetheless protective titers to diphtheria, tetanus and PRP occurred consistently. In contrast concomitant PRP-T with DTaP-eIPV enhanced the pertussis GMTs. CONCLUSIONS: We conclude that combined DTaP, eIPV and PRP-T in a single injection is well-tolerated and elicits an acceptable immune response to each component.

Adhesins, Bacterial↗

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age.

METHODS: In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections. RESULTS: There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.

Antibodies, Bacterial↗

Challenge of chimpanzees immunized with a recombinant canarypox-HIV-1 virus.

To evaluate the potential protective efficacy of a live recombinant human immunodeficiency virus type 1 (HIV-1) canarypox vaccine candidate, two chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant canarypox virus that expresses the HIV-1[IIIB(LAI)] gp120/TM, gag, and protease gene products. One month after the last booster inoculation, the animals were challenged by intravenous injection of cell-associated virus in the form of peripheral blood mononuclear cells from an HIV-1[IIIB(LAI)]-infected chimpanzee. One chimpanzee with a neutralizing antibody titer to HIV-1[IIIB(LAI)] of 128 at the time of challenge was protected, whereas both the second animal, with a neutralizing antibody titer of 32, and a naive control animal became infected. At 5 months after challenge, the protected chimpanzee and a third animal, previously immunized with various HIV-1[MN] antigens, were given a booster inoculation. The two animals were challenged intravenously 5 weeks later with twenty 50% tissue culture infectious doses of cell-free HIV-1[DH12], a heterologous subtype B isolate. Neither chimpanzee had neutralizing antibodies to HIV-1[DH12], and neither one was protected from infection with this isolate. The immune responses elicited by vaccination against HIV-1[IIIB(LAI)] or HIV-1[MN] did not, therefore, protect the animals from challenge with the heterologous cell-free HIV-1[DH12].

AIDS Vaccines↗

Normal and pathological changes in alpha rhythms.

Normal alpha rhythm begins to appear at three months. It was possible to observe successively, the rhythmicity, visual reactivity, occipital topography, and at the end of the first year, the first bursts of 7-8 Hz waves. Evolution of alpha was not linear with the age. Alpha frequency acceleration was important before the age of 11 years. In adults it decreased from 20 to 55, then there was a tendency to increase with aging. Amplitude was highest at 11-12 years, then its tendency was to decrease until 40, and to increase later. In pathology, for instance, alpha could be observed too early in newborn and infants with malformations, in children, in some psychiatric diseases, in adults and old people, alpha was replaced by theta waves in dementia: it seemed to be a very reliable sign, at the beginning of the disease.

Adolescent↗

Analysis of the antibody response in humans with a new inactivated hepatitis A vaccine.

Sera from subjects vaccinated with the Pasteur Merieux (PM) inactivated hepatitis A vaccine (AVAXIM) have been analysed in order: (1) to assess comparability of the results provided by a modified radio-immunoassay (mRIA) in the different laboratories involved in testings of sera during clinical trials and by enzyme-linked immunoabsorbent assay (ELISA) used during development of other inactivated hepatitis A vaccines; (2) to describe the IgM responses elicited by this vaccine compared with one control vaccine [HAVRIX, 720 ELISA antigens units; Smithkline Beecham (SB), Rixensart, Belgium]; (3) to provide comparative data between the PM vaccine and the SB vaccine on neutralizing activities of vaccine-induced antibodies. Vaccine-induced antibody titres evaluated by a mRIA in different laboratories correlated well and validated the comparability of the results obtained in various vaccine trials conducted by PM. Geometric mean titres (GMTs) expressed as milli-international units (mlU/ml) were higher with ELISA especially after the first dose, but seroconversion rates were similar and a good correlation was found between the two assays. IgM vaccine-induced antibodies were detectable in nearly all vaccinated subjects from week 2 after vaccination, with a peak titre between weeks 2 and 4 after the first dose. Comparison of GMTs by the Student Fisher t-test was statistically significant (P < 0.05) only at week 2 with higher titres in PM vaccinees. Neutralizing antibodies were detected after vaccination with the PM inactivated hepatitis A vaccine. The titres gradually increased between the second week after the first dose and the booster dose (week 24). A strong booster effect of the second dose on neutralizing titres was observed. Seroneutralizing titres induced at week 2 in subjects vaccinated with the PM inactivated hepatitis A vaccine were statistically significantly higher (P < 0.05) from those induced by the SB vaccine.

Adolescent↗