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Biomedical subjects

M Cadoz

Publications and source records attributed to M Cadoz.

At least 19 recordsLinked to original sources
PubMed2001

A canarypox vector-expressing cytomegalovirus (CMV) phosphoprotein 65 induces long-lasting cytotoxic T cell responses in human CMV-seronegative subjects.

The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.

Adolescent↗
PubMed2001

Formulations of single or multiple H. pylori antigens with DC Chol adjuvant induce protection by the systemic route in mice. Optimal prophylactic combinations are different from therapeutic ones.

The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol. This compound acts both as a formulating agent and as an adjuvant and induces a balanced Th1/Th2 response shown to be more effective for protection in our previous studies. Urease-DC Chol induced a significant protection in prophylaxis but not in therapeutic immunization. The protection level was between 1.5 and 2 log reduction of bacterial density measured by quantitative culture compared to unimmunized-infected mice. In parallel, the protective efficacy of other H. pylori antigens formulated in a similar way and administered with DC Chol was tested. These antigens were tested alone or in combination in prophylactic and therapeutic regimens. Some combinations of antigens induced a better prophylactic or therapeutic activity than urease alone (0.5-1.5 log further reduction in prophylaxis and therapy respectively, P<0.05). The combinations that induced the best protection were different in prophylaxis and therapy. In conclusion, DC Chol provides a convenient and efficient method to formulate different antigens even when they are present in non-compatible buffers initially. Moreover, the results obtained in protection against H. pylori with such formulations should lead the way to future clinical trials.

Adjuvants, Immunologic↗
PubMed2001

Assessment of Helicobacter pylori gene expression within mouse and human gastric mucosae by real-time reverse transcriptase PCR.

Despite increasing knowledge on the biology of Helicobacter pylori, little is known about the expression pattern of its genome during infection. While mouse models of infection have been widely used for the screening of protective antigens, the reliability of the mouse model for gene expression analysis has not been assessed. In an attempt to address this question, we have developed a quantitative reverse transcriptase PCR (RT-PCR) that allowed the detection of minute amounts of mRNA within the gastric mucosa. The expression of four genes, 16S rRNA, ureA (encoding urease A subunit), katA (catalase), and alpA (an adhesin), was monitored during the course of a 6-month infection of mice and in biopsy samples from of 15 infected humans. We found that the selected genes were all expressed within both mouse and human infected mucosae. Moreover, the relative abundance of transcripts was the same (16S rRNA > ureA > katA > alpA), in the two models. Finally, results obtained with the mouse model suggest a negative effect of bacterial burden on the number of transcripts of each gene expressed per CFU (P < 0.05 for 16S rRNA, alpA, and katA). Overall, this study demonstrates that real-time RT-PCR is a powerful tool for the detection and quantification of H. pylori gene expression within the gastric mucosa and strongly indicates that mice experimentally infected with H. pylori provide a valuable model for the analysis of bacterial gene expression during infection.

Animals↗
PubMed1999

A canarypox vector expressing cytomegalovirus (CMV) glycoprotein B primes for antibody responses to a live attenuated CMV vaccine (Towne).

To develop a vaccine against cytomegalovirus (CMV), a canarypox virus (ALVAC) expressing CMV glycoprotein (gB) was evaluated alone or in combination with a live, attenuated CMV vaccine (Towne). Three doses of 106.5 TCID50 of ALVAC-CMV(gB) induced very low neutralizing or ELISA antibodies in most seronegative adults. However, to determine whether ALVAC-CMV(gB) could prime for antibody responses, 20 seronegative adults randomly received either 106.8 TCID50 of ALVAC-CMV(gB) or 106.8 TCID50 of ALVAC-RG, expressing the rabies glycoprotein, administered at 0 and 1 month, with all subjects receiving a dose of 103.5 pfu of the Towne vaccine at 90 days. For subjects primed with ALVAC-CMV(gB), neutralizing titers and ELISA antibodies to CMV(gB) developed sooner, were much higher, and persisted longer than for subjects primed with ALVAC-RG. All vaccines were well tolerated. These results demonstrate that ALVAC-CMV(gB) primes the immune system and suggest a combined-vaccine strategy to induce potentially protective levels of neutralizing antibodies.

Adult↗
PubMed1997

A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal.

A randomized, double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted. A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months. Severe adverse events were monitored weekly during two visits after vaccination. Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days, in children under 15 years of age, was made by weekly home visits. Examining physicians, blind to vaccination status, took samples for culture and serologic testing. Pertussis was defined as 21 or more days of cough confirmed by culture, serology, or contact with a culture-confirmed person. Beginning 28 days after the third vaccine dose, the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group (RRac/wc) was 1.54 (95% CI, 1.23-1.93). In children younger than 18 months of age, RRac/wc was 1.16 (95% CI, 0.77-1.73) and 1.76 (95% CI, 1.33-2.33) in children older than 18 months, which suggests a shorter duration of protection with the acellular vaccine (P = 0.090). Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine: 31% (95% CI, 7-49) versus 55% against the protocol case definition, and 85% (95% CI, 66-93) versus 96% for the more severe WHO case definition. Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP, this difference was less prominent before 18 months of age, the customary age for a fourth dose. The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster-dose.

Adult↗
PubMed1996

Comparative safety and immunogenicity of an acellular versus whole-cell pertussis component of diphtheria-tetanus-pertussis vaccines in Senegalese infants.

A diphtheria and tetanus toxoid two-component acellular pertussis vaccine (DTaP), consisting of 25 micrograms glutaraldehyde-detoxified pertussis toxin (PT) and 25 micrograms native filamentous hemagglutinin (FHA), was compared with diphtheria and tetanus toxoid whole-cell pertussis vaccine (DTwP) in a randomized, double-blind manner in 286 Senegalese infants inoculated at two, four, and six months of age. In infants receiving DTaP a significantly lower rate of local reactions, crying and fever was observed than in infants receiving DTwP. One month after the third dose, the geometric mean titres for FHA antibodies were higher in the DTaP group, whereas increases in PT antibody titres were higher in the DTwP group. More than 90% of the infants had a fourfold or more increase in antibodies to both PT and FHA with either vaccine. Diphtheria, tetanus, and polio antibody responses were also measured and found to be comparable between the two groups. The results of this pilot study support the implementation of a field trial to compare the protective efficacy of these vaccines against pertussis in the same setting.

Antibodies, Bacterial↗
PubMed1995

The safety and use of canarypox vectored vaccines.

ALVAC recombinants have been administered to humans and animals by parenteral and oral routes without giving signs of replication, systemic dissemination or severe reaction. In principle, it should be impossible for canarypox recombinants to disseminate in the environment as they would not be synthesised in mammalian cells as complete virus. Canarypox vectors have been safe for humans, in whom there has been no evidence of replication, but more work needs to be done to prove absence of replication. Recombinants are immunogenic by the intramuscular and subcutaneous routes. They are also immunogenic when given orally, but the dose required is still under study. Canarypox recombinants effectively prime the immune system for induction of antibodies and CD8 cell-mediated cytotoxicity by protein antigens. Antibody responses are not influenced by prior inoculation of canarypox, of subunit vaccine corresponding to the gene insert, or of vaccinia. Canarypox virus is attenuated for canaries, in which species it is already widely used. In principle, it is non-infectious for humans or other mammals. It may be infectious for other birds.

AIDS Vaccines↗
PubMed1992

Immunisation with canarypox virus expressing rabies glycoprotein.

Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine. This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed.

Adult↗
PubMed1991

Prevention of travellers' diarrhoea by oral B-subunit/whole-cell cholera vaccine.

B-subunit/whole-cell cholera vaccine (BS-WC) has been shown to give Bangladeshi mothers and children only 3 months' protection against severe diarrhoea due to enterotoxigenic Escherichia coli (ETEC). Since a long-lasting effect is not necessary for protection against travellers' diarrhoea, a prospective double-blind study was conducted among tourists who went to Morocco from Finland. 307 tourists received two oral doses of BS-WC, whereas 308 controls received a placebo before departure. A research team went out with tourists and a laboratory for enteric pathogens was set up on location. A faecal specimen was taken from 100 randomly selected subjects before departure, from all travellers with diarrhoea, and routinely after return. Enteropathogenic bacteria were not isolated from any of the pre-departure specimens but were present during or after the holiday in 47% of tourists with travellers' diarrhoea, and in 14% of those without diarrhoea. BS-WC induced a 52% protection (p = 0.013) against diarrhoea caused by ETEC. The protection was better for mixed infections (65%, p = 0.016). The protective efficacy against a combination of ETEC and any other pathogen was 71% (p = 0.02), and that against ETEC plus Salmonella enterica even better at 82% (p = 0.01). Partial protection against travellers' diarrhoea is thus obtainable by active immunisation with BS-WC.

Administration, Oral↗
PubMed1991

The clinical and immunologic response of Chilean infants to Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine coadministered in the same syringe with diphtheria-tetanus toxoids-pertussis vaccine at two, four and six months of age.

The safety and immunogenicity of a vaccine against Haemophilus influenzae type b consisting of purified polyribosylribitolphosphate conjugated to tetanus toxoid (PRP-T) was evaluated in 278 Chilean infants who were randomly assigned to one of three treatment groups: Group A, PRP-T mixed with diphtheria-tetanus toxoids-pertussis (DTP) vaccine in a single syringe and given as a single inoculation in one arm and placebo in the other arm; Group B, PRP-T given in one arm and DTP in the other arm; Group C, DTP given in one arm and placebo in the other. Infants were immunized at 2, 4 and 6 months of age and examined daily for 4 days after each immunization; serum PRP antibodies were measured at baseline and 2 months after each dose. The only adverse systemic reaction attributable to PRP-T beyond that caused by DTP alone was a 7 to 20% increase in febrile responses in the first 24 hours after the first and second doses of vaccine; the fevers were largely low grade and not accompanied by increased irritability, diminished activity or loss of appetite, compared with the group who received DTP without PRP-T. After the first dose 72% of infants who received PRP-T combined with DTP and 67% who received it in a separate arm attained antibody concentrations greater than or equal to 0.15 micrograms/ml. After two doses of PRP-T, 93 and 95%, respectively, had concentrations greater than or equal to 0.15 microgram/ml and after three doses 100% of infants who received PRP-T had such titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1989

[Tolerance and immunogenicity of the capsular polyoside vaccine against Haemophilus influenzae type b. A study of 325 children 15 to 71 months of age].

The antigenic properties of the capsule polyoside (PRP) from Haemophilus influenzae type b (Hib) are adequate to form the basis for immunization designed to prevent the severe infections caused by this organism. The tolerance and immunogenicity of a vaccine containing either 12.5 or 25 micrograms PRP were studied in 325 healthy children aged 15 to 71 months after informed consent had been obtained from the parents. Each child was given one subcutaneous injection of 0.5 ml vaccine. Antibodies against Hib were assayed before and one month after the injection. Clinical tolerance was outstanding both locally (moderate and transient pain in 13% of cases) and systematically, with only eight (2.6%) febrile reactions in excess of 38.5 degrees C within 24 hours after the injection. A very significant rise in antibody titers was seen in all age groups, but a mean titer of 1 microgram/ml was achieved only in children aged 24 months or more. No significant difference was found between the two dosages. Individual analysis showed that following immunization antibody titers reached 0.15 micrograms/ml or more in 65% of infants aged 15 to 17 months, 71% of infants aged 18 to 23 months, 80% of infants aged 24 to 30 months and 95% of children older than 30 months. Despite the inadequate immune response evidenced in the younger age groups, our results confirm that Hib infections are preventable from the age of 2 years. Our results are consistent with those recorded with a similar vaccine in Finland.

Antibody Formation↗
PubMed1988

Acellular pertussis vaccines: evaluation of reversion in a nude mouse model.

An animal model has been developed to assess the safety of acellular pertussis vaccines in terms of reversion to toxicity. Adsorbed pertussis toxoid preparations, alone or combined in a DTP formulation, were administered to nude mice intraperitoneally. In parallel, groups of positive and negative control mice received pertussis toxin and buffer, respectively. The circulating white blood cells of the animals were monitored for 28 days. Mice immunized with glutaraldehyde toxoid preparations did not develop a lymphocytosis during the observation period, whereas mice immunized with an experimental formalin pertussis toxoid vaccine exhibited a high lymphocytosis six days after vaccine administration, demonstrating, in this model, a reversion of the toxoid. The nude mouse model thus appears to reveal the in-vivo reversion of pertussis toxoids and could be included in the quality control panel for the assessment of the safety of acellular pertussis vaccine.

Animals↗
PubMed1987

Protective activity of Vi capsular polysaccharide vaccine against typhoid fever.

The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide (CPS) was assessed in a randomised double-blind controlled trial. Vaccination of 11,384 children was followed by 21 months' surveillance. 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine and 19 cases in those vaccinated with Vi CPS. Protective efficacy was 60% calculated from the day of vaccination and 64% from 6 weeks after vaccination. Surveillance also included 11,691 unvaccinated children; 173 cases occurred in this group. Protective efficacy in relation to the unvaccinated group was 77.4% and 81.0% after 21 months, calculated immediately and 6 weeks after vaccination, respectively. Vaccination was associated with minimum local side-effects, and an increase in anti-Vi antibodies occurred, as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly raised at 6 and 12 months post vaccination. Vi CPS is thus a safe and effective means of typhoid vaccination.

Adolescent↗
PubMed1987

Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report.

We conducted a pilot study followed by a large clinical trial in Nepal of the use of the capsular polysaccharide of Salmonella typhi (Vi) as a vaccine to prevent typhoid fever. In the pilot study, involving 274 Nepalese, there were no significant side effects of the Vi vaccine; about 75 percent responded with a rise in serum antibodies of fourfold or more. In the clinical trial, residents of five villages were given intramuscular injections of either Vi or, as a control, pneumococcus vaccine dispensed in coded, randomly arranged, single-dose syringes. There were 6907 participants, of whom 6438 were members of the target population (5 to 44 years of age); each was visited every two days. Those with temperatures of 37.8 degrees C or higher for three consecutive days were examined and asked to give blood for culture. Typhoid was diagnosed as either blood culture-positive or clinically suspected on the basis of bradycardia, splenomegaly, and fever, with a negative blood culture. Seventeen months after vaccination, the codes were broken for the 71 patients meeting the criteria for either culture-positive or clinically suspected typhoid. The attack rate of typhoid was 16.2 per 1000 among the controls and 4.1 per 1000 among those immunized with Vi (P less than 0.00001). The efficacy of Vi was 72 percent in the culture-positive cases, 80 percent in the clinically suspected cases, and 75 percent in the two groups combined. These data provide evidence that Vi antibodies confer protection against typhoid. Surveillance continues to determine the duration of Vi-induced immunity.

Adolescent↗