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Biomedical subjects

M Slaoui

Publications and source records attributed to M Slaoui.

At least 19 recordsLinked to original sources
PubMed2004

The potential epidemiological impact of a genital herpes vaccine for women.

BACKGROUND: In two phase III vaccine trials immunisation of women previously uninfected by herpes simplex virus provided protection against genital herpes disease. In deciding policy, an evaluation of the epidemiological impact of the partial protection provided by the vaccine should be considered. METHODS: A sex and sexual activity stratified deterministic differential and partial differential equation model of the natural history of herpes simplex virus type 2 (HSV-2) and the impact of vaccination is developed and analysed. To explore the role of vaccination, the pattern of viral shedding and the transmission of infection during sexual acts within sexual partnerships are described. RESULTS: Using literature derived estimates of parameter values and assuming efficacy in only 40% of women the impact of the vaccine depends on assumptions made about its action. The vaccine has a limited impact if it only prevents disease but a more substantial impact if it reduces asymptomatic viral shedding, which it could do indirectly by preventing infection or directly by modifying the biology of the infection. Concern over the implications of a vaccine that prevents disease but has no impact on viral shedding was addressed in a worst case scenario. Here there is a modest increase in the incidence of infection in both men and women but an increase in disease prevalence in men alone, since the virus directly protects some women from disease. CONCLUSIONS: Results suggest that a herpes vaccine should be used universally and that a vaccine that only protects HSV-1-/2- women can paradoxically have a significant epidemiological impact, the scale of which depends upon changes in patterns of viral shedding.

Clinical Trials, Phase III as Topic↗
PubMed2001

Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of formalin-inactivated respiratory syncytial virus vaccine-induced disease.

The mechanisms by which administration of a formalin-inactivated respiratory syncytial virus vaccine resulted in enhanced disease among children after they later became naturally infected with the virus remains largely undefined. After immunization and live virus challenge, the cotton rat demonstrated the histopathologic marker of the enhanced disease, polymorphonuclear leukocyte infiltration of lung alveolar spaces. We now report that immunization with formalin-inactivated vaccine formulated with the adjuvant, 3-deacylated monophosphoryl lipid A, dramatically reduces or eliminates the polymorphonuclear leukocyte infiltration within the alveoli of cotton rats post-challenge. We suggest, that this or similar adjuvants may be beneficial components of candidate non-replicating respiratory syncytial virus vaccines, whose development has been hampered by safety concerns.

Adjuvants, Immunologic↗
PubMed2000

A hepatitis B vaccine formulated with a novel adjuvant system.

Although more than 95% of the vaccinated population responds to the currently licensed vaccines against hepatitis B, some groups were found to be low responders. Lipid A as adjuvant, through its ability to activate macrophages, might improve humoral as well as cellular immune response. Therefore we evaluated the profile of a hepatitis B vaccine with the new adjuvant system SBAS4. 150 young adults were enrolled and randomized into three groups: one received the SBAS4 hepatitis B vaccine, the second Engerix-B(TM) and the third a hepatitis B vaccine with an alternative formulation on alum. Vaccinations were at 0 and 6 months. The vaccine was well tolerated. At month 7 all vaccinees were protected but with significant differences in GMTs between groups: 13,271 mIU/ml for the SBAS4 group versus 1203 and 1823 mIU/ml. Hence the hepatitis B vaccine with the new adjuvant system is more immunogenic compared to the other vaccines containing the same antigen and could be suitable for a two dose schedule.

Adjuvants, Immunologic↗
PubMed1999

Cellular immune response of a varicella vaccine following simultaneous DTaP and VZV vaccination.

BACKGROUND: Chickenpox and zoster are an important cause of morbidity among children and adults. The ability of a new, thermostable vaccine to induce varicella-zoster-virus (VZV)-specific humoral and cell mediated immunity when given simultaneously with diphtheria-tetanus-acellular pertussis vaccine (DTaP) as a booster dose in the second year of life was investigated. METHODS: A new, temperature stable varicella vaccine (OKA-strain, SB-Biologicals, Rixensart, Belgium) was given simultaneously with a booster dose of DTaP vaccine. VZV-specific humoral and cell-mediated immunity was studied in the first 27 out of 232 vaccinated children at 16-28 months of age, from blood samples drawn just before and six weeks after vaccination. VZV-specific antibody response, T-cell proliferation, cytokine production and expression of activation markers (CD25, HLADR) on T-cells were analyzed. RESULTS: Vaccination resulted in a significant rise of VZV-specific serum IgG titers and in a strong VZV-specific T-cell response in all vaccinated infants. Analysis of the expression of activation marker revealed activation of both CD4+-T-helper- and CD8+-T-cells. CONCLUSIONS: The varicella vaccine given simultaneously with DTaP produced strong B- and T-cell responses alike. This is the first report to show that CMI to VZV is conferred to young children by vaccination with a temperature stable VZV vaccine.

Antibodies, Viral↗
PubMed1999

Potent induction of focused Th1-type cellular and humoral immune responses by RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine.

The RTS,S/SBAS2 vaccine confers sterile protection against Plasmodium falciparum sporozoite challenge. The mechanisms underlying this are of great interest, yet little is known about the immune effector mechanisms induced by this vaccine. The immune responses induced by RTS,S/SBAS2 were characterized in 10 malaria-naive volunteers. Several epitopes in the circumsporozoite protein (CSP) were identified as targets of cultured interferon (IFN)-gamma-secreting CD4+ T cells. RTS,S-specific IFN-gamma-secreting effector T cells were induced in 8 subjects; this ex vivo response mapped to a single peptide in Th2R. CSP-specific CD8+ cytotoxic T lymphocytes were not detected. RTS, S-specific IFN-gamma production was universal, whereas interleukin-4 and -5 production was rare. RTS,S-specific lymphoproliferative responses and antibodies to CSP were strongly induced in all volunteers. Responses waned with time but were boostable. Thus, RTS, S/SBAS2 is a potent inducer of Th1-type cellular and humoral immunity. These results highlight possible immune mechanisms of protection and have important implications for vaccine design in general.

Adult↗
PubMed1999

Pulmonary lesions in primary respiratory syncytial virus infection, reinfection, and vaccine-enhanced disease in the cotton rat (Sigmodon hispidus).

Infection of the cotton rat lung with a human strain of respiratory syncytial virus results in substantial virus replication and is associated with mild-to-moderate peribronchiolitis, perivasculitis, and bronchitis. Reinfection after 49 days did not result in detectable virus replication, but surprisingly, was associated with an earlier appearance and accentuation of the three types of lesions seen in cotton rats undergoing primary infection. Animals primed with formalin-inactivated virus and challenged after 49 days had pulmonary viral titers 1/10 to 1/100 of that seen in naive animals, but developed markedly accentuated lesions of the same type as in animals undergoing primary or secondary infection. In addition, the animals with the vaccine-enhanced disease developed alveolitis and interstitial pneumonitis, which seem to be specific markers for the vaccine enhancement. These latter markers may be useful in determining the safety of nonreplicating vaccines.

Animals↗
PubMed1998

Safety and immunogenicity of a hepatitis B vaccine formulated with a novel adjuvant system.

A formulation of recombinant hepatitis B surface antigen (HBsAg) combined with a novel adjuvant system, SBAS4--a combination of aluminium salt and monophosphoryl lipid A (MPL), was assessed in 27 healthy adult volunteers with a commercial vaccine (Engerix-B) as control. After three doses (0, 1, 6 months schedule), reactogenicity profiles were similar. Local reactions were essentially mild, the most frequent being soreness at the injection site. Seroprotection was achieved after two doses in all subjects given the candidate vaccine, all Engerix-B vaccines being seroprotected after the third dose. After the second and third doses, higher anti-HBs Geometric Mean Titres (GMTs) were observed in the group which received the formulation with the novel adjuvant system, and cellular immunity, measured as HBsAg-specific lymphoproliferation was stronger than with Engerix-B. These results indicate that the new formulation is safe, well-tolerated and immunogenic and may promote more rapid protection against hepatitis B infection.

Adjuvants, Immunologic↗
PubMed1998

Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine.

The malaria sporozoite vaccine candidate RTS,S, formulated with an oil-in-water emulsion plus the immunostimulants monophosphoryl lipid A and the saponin derivative QS21 (vaccine 3), recently showed superior efficacy over two other experimental formulations. Immunized volunteers were followed to determine the duration of protective immune responses. Antibody levels decreased to between one-third and one-half of peak values 6 months after the last dose of vaccine. T cell proliferation and interferon-gamma production in vitro were observed in response to RTS,S or hepatitis B surface antigen. Seven previously protected volunteers received sporozoite challenge, and 2 remained protected (1/1 for vaccine 1, 0/1 for vaccine 2, and 1/5 for vaccine 3). The prepatent period was 10.8 days for the control group and 13.2 days for the vaccinees (P < .01). Immune responses did not correlate with protection. Further optimization in vaccine composition and/or immunization schedule will be required to induce longer-lasting protective immunity.

Adolescent↗
PubMed1998

Development and efficacy assessment of combination vaccines, with emphasis on acellular pertussis.

The number of vaccines suitable for infant immunization is increasing, leading to a need to co-administer them in combination or combos. The recent demonstration of high efficacy against whooping cough using DTPa vaccines makes it desirable to administer combos such as DTPaHBIPVHib. For all vaccines included, surrogate markers for protection exist, except for pertussis. The field efficacy studies performed with DTPa vaccines did not allow the establishment of a correlate for protection. We propose to use detailed serology and cell-mediated immunity markers obtained from infant immunization studies, as well as a mouse intranasal challenge model, to monitor the immune responses induced by DTPa-combos.

Animals↗
PubMed1997

A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group.

BACKGROUND: The candidate vaccines against malaria are poorly immunogenic and thus have been ineffective in preventing infection. We developed a vaccine based on the circumsporozoite protein of Plasmodium falciparum that incorporates adjuvants selected to enhance the immune response. METHODS: The antigen consists of a hybrid in which the circumsporozoite protein fused to hepatitis B surface antigen (HBsAg) is expressed together with unfused HBsAg. We evaluated three formulations of this antigen in an unblinded trial in 46 subjects who had never been exposed to malaria. RESULTS: Two of the vaccine formulations were highly immunogenic. Four subjects had adverse systemic reactions that may have resulted from the intensity of the immune response after the second dose, which led us to reduce the third dose. Twenty-two vaccinated subjects and six unimmunized controls underwent a challenge consisting of bites from mosquitoes infected with P. falciparum. Malaria developed in all six control subjects, seven of eight subjects who received vaccine 1, and five of seven subjects who received vaccine 2. In contrast, only one of seven subjects who received vaccine 3 became infected (relative risk of infection, 0.14; 95 percent confidence interval, 0.02 to 0.88; P<0.005). CONCLUSIONS: A recombinant vaccine based on fusion of the circumsporozoite protein and HBsAg plus a potent adjuvant can protect against experimental challenge with P. falciparum sporozoites. After additional studies of protective immunity and the vaccination schedule, field trials are indicated for this new vaccine against P. falciparum malaria.

Adjuvants, Immunologic↗
PubMed1997

Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine.

UNLABELLED: The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP) in very young infants (< 18 months) can be overcome by conjugating PRP to a T-cell dependent carrier protein. We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5 months of age induced PRP-specific immunological memory, by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later. The unconjugated PRP elicited protective anti-PRP antibody levels (> or = 0.15 microgram/ml) in all but 3 of the 369 vaccinees, including 13 infants who failed to demonstrate a measurable immune response after the primary course. In a sub-cohort of 54 subjects all had anti-PRP levels > or = 0.5 microgram/ml within 7-14 days of the booster showing a rapid anamnestic type response. Both primary and booster responses were predominantly IgGl indicating a T-cell dependent response. The DTPa-HBV components elicited protective anti-diphtheria, anti-tetanus and anti-HBs antibody levels in > or = 98.5% of vaccinees, and immune responses to each of the acellular pertussis vaccine components in 92.3%-97.3% of subjects. CONCLUSION: The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response, but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP, indicating that protection against circulating wild-type Hib had been generated. Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course. Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine, when administered separately or as a single injection in the same syringe, in primary immunisation schedules at 3, 4 and 5 months of age.

Age Factors↗
PubMed1997

Adjuvants influence the quantitative and qualitative immune response in BALB/c mice immunized with respiratory syncytial virus FG subunit vaccine.

The ability of monophosphoryl lipid A (MPL), QS-21 and alum to alter the immunologic response to immunization with respiratory syncytial virus a chimeric FG construct (FG) subunit vaccine was examined in BALB/c mice. FG/MPL, FG/alum, and FG/MPL/QS-21 combinations increased non-neutralizing antibody response, while FG/QS-21 did not. FG subunit vaccine with MPL, QS-21, or both had cytokine responses more closely resembling primary infection than FG/alum, with decreased interleukin-4 mRNA levels and increased IgG2a isotype antibody. The lungs of the mice immunized with FG subunit vaccines showed a heightened inflammatory response to respiratory syncytial virus challenge as compared to live virus immunization. Adjuvants can be used to alter the humoral and cellular responses to RSV subunit immunization.

Adjuvants, Immunologic↗
PubMed1997

Efficacy of a recombinant glycoprotein D subunit vaccine on the development of primary and recurrent ocular infection with herpes simplex virus type 1 in mice.

The protective efficacy of a glycoprotein D subunit vaccine (gD2 SB AS4) was evaluated in a mouse model of human recurrent herpetic stromal keratitis (HSK). When administered before primary infection, gD2 SB AS4 protected mice against corneal pathology, mortality, and latency resulting from ocular viral challenge with herpes simplex virus type 1 (HSV-1) McKrae strain. In addition, gD2 SB AS4 significantly decreased postreactivation corneal disease. A control vaccine, gD2 alum, protected against acute ocular infection only. When administered after primary infection, gD2 SB AS4 vaccination decreased postreactivation ocular shedding but had no other significant effects. Vaccination with gD2 SB AS4 was associated with high anti-gD antibody responses and low delayed-type hypersensitivity responses. These results have identified a prophylactic vaccine, gD2 SB AS4, with activity against acute and recurrent HSK in mice and emphasize the need for vaccine evaluation in both primary and recurrent ocular herpetic disease models.

Animals↗
PubMed1997

Seroprevalence of herpes simplex virus types 1 and 2 and cytomegalovirus in adolescents.

We determined the prevalence of herpes simplex virus (HSV) and cytomegalovirus (CMV) antibodies in a cohort of adolescents 12 to 22 years of age in anticipation of the development of vaccines to control HSV and CMV infections. For the overall study population, we found that 62% were seropositive for HSV type 1 (HSV-1), 12% were seropositive for HSV type 2 (HSV-2), and 65% were seropositive for CMV. Race was not related to HSV-1 seropositivity, but African-American adolescents were more likely than Caucasian adolescents to be seropositive for HSV-2 and CMV. Girls also were more likely than boys to be seropositive for HSV-2 and CMV. For boys, history of a sexually transmitted disease was identified as a risk factor for HSV-2 seropositivity; for girls, a greater number of sexual partners increased the risk of being seropositive for HSV-2. Our data demonstrating a high prevalence of infection during adolescence suggest that immunization for HSV-1, HSV-2, and CMV may need to occur in childhood.

Adolescent↗
PubMed1997

Cell-mediated immunity after pertussis vaccination and after natural infection.

The aim of this study was the investigation of the specific cell-mediated (CMI) responses induced by DTaP and to compare these data to immunity after natural infection. The ability of peripheral blood T-lymphocytes to respond to the pertussis related antigens pertussis-toxin (PT), filamentous haemagglutinin (FHA), and Pertactin (PRN) was investigated in 40 children before vaccination and at different times after vaccination with DTaP (Infanrix) by measurement of antigen-specific proliferation, lymphocyte phenotype, cytokine production and expression of activation markers (CD25, HLADR). Similar investigations were performed in children 4-6 weeks after recovery from natural pertussis. DTaP created a specific T-cell-response to PT, FHA and PRN that increased continually, depending on the progress of the vaccination schedule. In contrast to waning antibody titres, CMI was stable even between the post-basic vaccination and the pre-booster period. The magnitude of CMI after DTaP equalled those after natural infection. Measurement of cytokine-pattern showed induction of IFN-tau-producing T-helper-1-cells with lower stimulation of IL 10-producing T-helper-2-cells for DTaP and natural infection. Our data indicate that DTaP-vaccination induces a potent immune response to PT, FHA, and PRN at least equivalent to CMI after natural infection. The finding of a preferential T-helper-1-induction after DTaP and natural infection suggests a role of IFN gamma-activated macrophages in the protective response against B. pertussis-induced disease.

Adhesins, Bacterial↗
PubMed1996

Pertussis-specific cell-mediated immunity in infants after vaccination with a tricomponent acellular pertussis vaccine.

The aim of this study was to investigate pertussis-specific cell-mediated immunity in infants vaccinated with a tricomponent acellular vaccine. Infants were investigated during a primary vaccination schedule from the third month of life to the sixth month as well as before and after a booster at 15 to 24 months. This is the first report of specific cell-mediated immune responses to pertussis-related antigens in infants below the age of 12 months. Our data show that the vaccine induces T-cell responses specific for the vaccine components, detoxified pertussis toxin, filamentous hemagglutinin, and pertactin, that increase progressively over the course of the vaccination schedule. In contrast to declining antibody titers, cell-mediated immune responses are stable over the postprimary to prebooster period. Vaccination results in a progressive increase in the number of T cells that express activation marker CD45RO preferentially on CD4-positive T cells after stimulation with pertussis antigens. Measurements of cytokine secretion profiles demonstrated a preferential induction of interleukin 2- and gamma interferon-producing T-helper 1 cells and only low production of interleukin 10. The observed persistence of the specific cell-mediated immunity may have a bearing on the protective mechanisms induced by pertussis vaccination. Cell-mediated immunity requires further study, particularly to improve our understanding of the persistence of protection afforded by vaccination up to the administration of booster doses.

Antibodies, Bacterial↗