Biomedical subjects

C A Siegrist

Publications and source records attributed to C A Siegrist.

At least 19 recordsLinked to original sources

PubMed2006

Influence of genetic and environmental factors on the immunogenicity of Hib vaccine in Gambian twins.

The differences in incidence rates of Haemophilus influenzae type b disease and the variation in Hib conjugate vaccine efficacy achieved among different ethnic groups suggest genetic influences on the immune response to Hib vaccine. The serum anti-PRP antibody concentration of 43 monozygotic (MZ) and 147 dizygotic (DZ) twin pairs in the Gambia was measured using a standardised Hib ELISA. Intrapair correlations for MZ and DZ twin pairs were compared and heritability in antibody responses to Hib conjugate vaccine was estimated to be 51% (95% CI: 32-66%), indicating a significant genetic contribution in the response. We conclude that genetic factors may be involved in the variation in immune response to Hib vaccine observed in different populations and may contribute to cases of vaccine failure.

Antibodies, Bacterial↗

PubMed2006

[Vaccinology update 2005: a new category of recommendations for optimal vaccine protection].

A new category of vaccination recommendation was introduced to increase the equity of the access to the information that relatively rare but severe diseases may be prevented by immunization. This decision was supported by the observation of a 2-level vaccination practice in Switzerland, reflected by the fact that children from paediatrician parents are better immunized than other children. The introduction of "additional recommended vaccinations" to the baseline immunizations should correct this inequity. In 2006, parents may choose to protect their children against meningitis and invasive diseases caused by pneumococcus or group C meningococcus. The challenge is now to inform parents about this new possibility of an optimal prevention, in addition to baseline immunizations.

Child↗

PubMed2005

[Recurrent lower respiratory tract infection in children: when and how should they be investigated?].

Children with recurrent lower respiratory tract infections are often a challenge for their physicians. This article reviews the differential diagnosis of recurrent cough, bronchopneumonia and/or pneumonia in children and emphasizes on the necessity of preventing long-term complications of these infections. It also suggests a step-wise immunological work-up, which includes investigating a possible immune maturation delay or deficiency which could explain these symptoms. This work-up focuses on measuring antibody responses to pneumococci, followed by immunization when necessary, to rule out B cell dysfunction. Finally, this article also describes an upcoming study in Switzerland which will evaluate in 2005 the clinical and immunological outcome of these young patients.

Antibodies, Bacterial↗

PubMed2005

[Vaccinology update 2004].

In 2004, the most important changes have been the necessity of adapting our vaccine strategies to the persistent risk of measles in Switzerland (infant immunization, catch-up until 40 years of age) and a better identification of those at high risk of infectious disease complications. This includes a first definition of those at high risk of complications from chickenpox, to which adolescents and young adults without a positive history of chicken-pox will be added in 2005. Certain "old vaccines" have been replaced by novel formulations. And new clinical studies have again contributed to provide the data needed to meet the expectations of some worried patients. What did not change in 2004 ? The Internet address allowing physicians to send any question related to vaccination: www.infovac.ch

Adolescent↗

PubMed2005

[Consequences of an unsufficient range of immunity in "pediatric" infectious diseases--example with measles].

From January to February 2005, the healthcare authorities of the Canton of Geneva were alerted to 15 cases of measles, in contrast to one single case in 2004. The adult status (17-44 years) of the affected persons years was unusual. Four were health care workers at the same hospital who were infected after contact with a 44-year-old patient in a single night during his stay in the emergency room. The presumption that measles are only a paediatric disease had made the diagnosis difficult. None of all these adults was immune according to the actual recommendations. Despite a federal vaccine policy, repetition of recommendations, good results of available vaccines and reimbursement of the cost by health insurance companies, voluntary vaccination prevalence is too small in Switzerland to prevent the outbreak of epidemics. In contrast to the goals of the World Health Organization (WHO) and the Swiss Federal Office of Public Health, the country is unfortunately far from displaying a sufficiently high herd immunity to prevent health care-associated and economic damage by sporadic epidemics.

Communicable Disease Control↗

PubMed2001

Nosocomial outbreak of multiple bloodborne viral infections.

In resource-limited countries, nosocomial transmission of bloodborne pathogens is a major public health concern. After a major outbreak of human immunodeficiency virus (HIV) infection in approximately 400 children in 1998 in Libya, we tested HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) markers in 148 children and collected epidemiological data in a subgroup of 37 children and 46 parents. HIV infection was detected in all children but one, with HCV or HBV coinfection in 47% and 33%, respectively. Vertical transmission was ruled out by analysis of parents' serology. The children visited the same hospital 1-6 times; at each visit, invasive procedures with potential blood transmission of virus were performed. HIV and HCV genotypic analyses identified a HIV monophyletic group, whereas 4 clusters of HCV sequences were identified. To our knowledge, this is the largest documented outbreak of nosocomial HIV transmission.

Adult↗

PubMed2001

Induction of adult-like antibody, Th1, and CTL responses to measles hemagglutinin by early life murine immunization with an attenuated vaccinia-derived NYVAC(K1L) viral vector.

Although initially developed in adult animals, novel viral vectors expressing recombinant measles antigens must eventually prove their success in the early life setting, where the efficacy of the currently used live-attenuated measles virus vaccine is limited. The immunological requirements for vaccine candidates include the generation of protective antibody responses as well as the induction of Th1 and cytotoxic T lymphocytes (CTL) responses, which is challenging in the neonatal setting. Here, we report that young BALB/c mice immunized with a single dose of a vaccinia-based NYVAC(K1L) vector generate adult-like antihemagglutinin (HA) antibody responses as well as adult-like Th1 and CTL responses. Despite this strong immunogenicity in early life, antibody responses (but not T-cell responses) to a single dose of NYVAC(K1L)-HA remained susceptible to inhibition by preexisting measles antibodies, calling for use of prime-boost strategies. NYVAC(K1L)-HA is the first attenuated live viral vector demonstrated as capable of inducing adult-like antibody, Th1, and CTL responses against measles in an early life murine immunization model, a capacity previously only reported for measles DNA vaccines.

Animals↗

PubMed2001

Neonatal and early life vaccinology.

Preclinical and human vaccine studies indicate that, although neonatal immunisation does not generally lead to rapid and strong antibody responses, it may result in an efficient immunological priming, which can serve as an excellent basis for future responses. The apparent impairment of CD4 and CD8 T-cell function in early life seems to result from suboptimal antigen-presenting cells-T cell interactions, which can be overcome by use of specific adjuvants or delivery systems. Although persistence of maternal antibodies may limit infant antibody responses, induction of T-cell responses largely remain unaffected by these passively transferred antibodies. Thus, neonatal priming and early boosting with vaccine formulations optimised for sufficient early life immunogenicity and maximal safety profiles, could allow better control of the huge infectious disease burden in early life.

Animals↗

PubMed2001

Delayed and deficient establishment of the long-term bone marrow plasma cell pool during early life.

Early life antibody responses are characterized by a rapid decline, such that antigen-specific IgG antibodies decline to baseline levels within months following infant immunization. This generic observation remains unexplained. Here, we have analyzed the induction and organ-localization of antigen-specific IgG antibody-secreting cells (ASC) following immunization of 1-week-old or adult BALB/c mice with tetanus toxoid (TT), a T-dependent antigen. Early life priming induced only slightly lower numbers of TT-specific IgG ASC in the spleen, and these reached adult levels following repeat immunization. In contrast, early life immunization generated much fewer bone marrow plasma cells than in adults, even after boosting. A similar limitation of the natural development of the bone marrow pool of ASC was observed. Transfer experiments with adult or early life spleen ASC indicated limited homing of TT-specific adult ASC to the bone marrow of 4-week-old mice as compared to adult recipients, whereas homing patterns were similar when early life or adult ASC were transferred into adult recipients. These observations suggest that a limited bone marrow B cell homing capacity and, as a result, relatively deficient bone marrow ASC responses, are critical factors which may explain the limited persistence of IgG antibodies to T-dependent antigens in early life.

Adoptive Transfer↗

PubMed2001

[The child with recurrent infections: which screening for immunoe deficiency?].

A child with recurrent infections represents a challenge to the pediatrician who must identify, among a large number of repeatedly infected but nevertheless healthy children whose parents need to be reassured, the rare cases of potentially severe immune deficiency. This can be most successfully achieved through the measurement of IgA, IgG, and antibody titers to vaccine (tetanus, diphtheria, Haemophilus influenzae B) and exposure (pneumococcus) antigens. The presence of normal antibody responses makes it possible to rule out underlying immune deficiency in a sensitive and specific manner. Conversely, abnormally weak antibody responses identify the children who have to be referred without delay for further investigation of a potential immune defect. This article indicates for which pediatric patients an immunodeficiency screening should be considered, and how to analyze its results.

Algorithms↗

PubMed2001

Adjuvant effects of CpG oligodeoxynucleotides on responses against T-independent type 2 antigens.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) are potent in vitro B-cell activators and they have been successfully used to increase in vivo antibody responses to T-dependent peptide and protein antigens. In contrast, the use of CpG-ODN to enhance in vivo antibody responses to various T-independent type 2 (TI-2) antigens has recently generated contradictory results. In this study, we compared the CpG-ODN stimulatory effect on antibody responses of adult and young BALB/c mice to trinitrophenylaminoethyl-carboxymethyl (TNP) -Ficoll and to polysaccharides (PS) from several distinct serotypes of Streptococcus pneumoniae (SPn). CpG-ODN co-administration significantly enhanced antigen-specific immunoglobulin M (IgM), IgG, IgG1 and IgG2a titres to TNP-Ficoll. The depletion of CD4+ cells by monoclonal antibodies (GK1.5) identified their essential role in CpG-ODN-mediated enhancement of antibody responses. In contrast to TNP-Ficoll, CpG-ODN failed to enhance IgM and IgG responses to any of the 18 SPnPS serotypes tested. Providing T-cell epitopes by the conjugation of SPnPS to the carrier protein tetanus toxoid again allowed CpG-ODN to mediate enhancement of IgG, IgG2a and IgG3 responses to most SPnPS serotypes. Thus, antigen-presenting cell/T-cell interaction appears to largely mediate the in vivo influence of CpG-ODN on antibody responses to TI-2 antigens. In early life, additional factors limit CpG-ODN modulation of antibody responses to TI-2 antigens.

Adjuvants, Immunologic↗

PubMed2001

Epidemiology of herpes simplex virus in children by detection of specific antibodies in saliva.

OBJECTIVES: To facilitate the study of the prevalence of herpes simplex virus (HSV) infection and its determinants in children, we developed a noninvasive saliva test. METHODS: A capture enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to HSV in saliva was developed, validated against a commercial serum ELISA in 110 children and 187 adults and used in a cross-sectional population-based study including 2,048 children ages 1 to 17 years, recruited in day-care centers and schools of Geneva, Switzerland. Demographic and socioeconomic determinants of HSV prevalence were studied. RESULTS: The sensitivity and specificity of the saliva assay were 94.1 and 95.5%, respectively, compared with the commercial serum ELISA. Participation in the cross-sectional study was 86.6%. The overall prevalence of anti-HSV IgG was 23.91%. It increased with age up to 7 years, reaching a plateau at 35% without evidence for day-care or school transmission. The main determinants of prevalence were region of national origin and parents' professional category. CONCLUSIONS: This new saliva-based assay proved its feasibility in the first population-based study of HSV prevalence in children that uses saliva, confirmed its validity by identifying determinants of prevalence consistent with previous reports and yielded new information, such as the lack of influence of day-care attendance, in the population studied.

Adolescent↗

PubMed2001

Priming of immune responses to hepatitis B surface antigen in young mice immunized in the presence of maternally derived antibodies.

Early vaccination is necessary to protect infants from various infectious diseases. However, this is often unsuccessful largely due to the immaturity of the neonatal immune system. Furthermore, maternally derived antibodies can interfere with active immunization. We have previously shown in young mice that immune responses against several different antigens can be improved by the addition of oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN). In this study we have evaluated immunization of newborn (1-7-day-old) BALB/c mice against hepatitis B surface antigen (HBsAg), with alum and/or CpG ODN, in the presence of high levels of maternal antibody against HBsAg (anti-HBs). Seroconversion rates and anti-HBs titers were compared to those induced by a HBsAg-expressing plasmid, since other studies had suggested DNA vaccines to be superior to protein vaccines in young mice with maternal antibody. HBsAg/alum/CpG ODN was superior to DNA vaccine in inducing HBsAg-specific CTL responses in young mice in the presence of maternally transferred anti-HBs antibodies. However, B cell responses to both HBsAg/alum/CpG ODN and DNA vaccines remained weak in the presence of maternally transferred anti-HBs antibodies.

Adjuvants, Immunologic↗

PubMed2001

The search for novel adjuvants for early life vaccinations: can "danger" motifs show us the way?

Potent but safe adjuvants are required to circumvent the many limitations of the newborn immune system to induce rapidly effective and long lasting immunity to subunit vaccines. By the use of pattern recognition receptors, antigen-presenting cells (APC) can very efficiently be activated by "danger" motifs expressed by various pathogens. APC activated by "danger" motifs, such as immunostimulatory sequences of bacterial DNA, can not only transmit the activation signal from the innate immunity to the adaptive compartment, but also shape the antigen-specific immune responses. Molecules or compounds expressing "danger" motifs could, therefore, be considered for use as adjuvants for subunit vaccines. In this review, the authors discuss the promises and potential drawbacks that such novel adjuvants could hold for their use in experimental and clinical early life vaccinations.

Adjuvants, Immunologic↗

PubMed2000

Recovery of immune reactivity after T-cell-depleted bone marrow transplantation depends on thymic activity.

To evaluate the importance of the thymus for the reconstitution of immunity in recipients of a T-cell-depleted bone marrow, we measured the appearance of CD4(+)CD45RA(+)RO(-) naive T cells (thymic rebound), restoration of the diversity of the T-cell-receptor (TCR) repertoire and the response to vaccinations with tetanus toxoid (TT). Repopulation by CD4(+)CD45RA(+)RO(-) thymic emigrants varied among patients, starting at approximately 6 months after transplantation. Young patients reconstituted swiftly, whereas in older patients, the recovery of normal numbers of naive CD4(+) T cells could take several years. Restoration of TCR diversity was correlated with the number of naive CD4(+)CD45RA(+)RO(-) T cells. Moreover, the extent of the thymic rebound correlated with the patient's capacity to respond to vaccinations. Patients without a significant thymic rebound at the moment of vaccination (CD4(+)CD45RA(+)RO(-) T cells less than 30 microL) did not respond, or responded only marginally even after 3 boosts with TT. We conclude that during the first year after transplantation, the absence of an immune response is due mainly to the loss of an adequate T-cell repertoire. Restoration of the repertoire can come only from a thymic rebound that can be monitored by measuring the increase of CD4(+)CD45RA(+)RO(-) naive T cells. This will allow postponing revaccinations to a moment when the patient will be able to respond more effectively. This may be particularly useful in the elderly patient who, owing to low thymic activity, might not yet be able to respond 1 year after transplant when revaccinations are usually scheduled.

Adolescent↗

PubMed2000

Limitations of in vivo IL-12 supplementation strategies to induce Th1 early life responses to model viral and bacterial vaccine antigens.

The limited induction of Th1 and cytotoxic immune responses is regarded as the main reason for the increased susceptibility to intracellular microorganisms in early life. Recently, in vitro IL-12 supplementation was shown to enhance the limited IFN-gamma release of measles-specific infant T cells. Using a series of IL-12 delivery systems, we show here that in vivo IL-12 supplementation may enhance early life murine Th1 responses to two model vaccine antigens, measles virus hemagglutinin and tetanus toxin peptide. However, this required multiple repeat injections of recombinant rIL-12, which were poorly tolerated in young mice. Local IL-12 delivery by an IL-12 expressing canarypox vector proved safe but failed to modulate vaccine responses. An IL-12 DNA plasmid or a CD40L DNA plasmid efficiently enhanced neonatal Th1 responses to measles hemagglutinin DNA vaccine. However, both plasmids only enhanced Th1 responses to DNA and not to peptide, protein, or live viral vaccines. Thus, inducing adult-like Th1 responses may be achieved in vivo by inducing (CD40L) or substituting for (IL-12 supplementation) optimal activation of neonatal APC. However, these immunomodulatory effects appear limited to certain antigen-presentation approaches and may not be broadly applicable to vaccines.

Adjuvants, Immunologic↗

PubMed2000

Expression of MHC class II molecules contributes to lipopolysaccharide responsiveness.

Activation of phagocytes by lipopolysaccharide (LPS) causes synthesis and secretion of various mediators of inflammation. CD14, a glycosylphosphatidylinositol-anchored monocytic antigen serving as receptor for LPS, and members of the family of Toll-like receptors mediate cellular activation in response to LPS. Here we investigated whether expression of MHC class II molecules modified the response to LPS. Comparing LPS responsiveness of human and murine cells differing for expression of MHC class II molecules, we found that lack or a low level of expression of MHC class II molecules resulted in diminished secretion of pro-inflammatory cytokines following stimulation with LPS. Thus, expression of MHC class II molecules modifies LPS responsiveness, a finding suggesting that these molecules contribute to the pathogenesis not only of exotoxin-triggered toxic shock but also of endotoxin-triggered septic shock. Additionally to their role in antigen-specific immunity MHC class II molecules may influence the inflammatory response triggered by microbial constituents.

Animals↗

PubMed2000

CD4(+) T-cell-mediated antiviral protection of the upper respiratory tract in BALB/c mice following parenteral immunization with a recombinant respiratory syncytial virus G protein fragment.

We analyzed the protective mechanisms induced against respiratory syncytial virus subgroup A (RSV-A) infection in the lower and upper respiratory tracts (LRT and URT) of BALB/c mice after intraperitoneal immunization with a recombinant fusion protein incorporating residues 130 to 230 of RSV-A G protein (BBG2Na). Mother-to-offspring antibody (Ab) transfer and adoptive transfer of BBG2Na-primed B cells into SCID mice demonstrated that Abs are important for LRT protection but have no effect on URT infection. In contrast, RSV-A clearance in the URT was achieved in a dose-dependent fashion after adoptive transfer of BBG2Na-primed T cells, while it was abolished in BBG2Na-immunized mice upon in vivo depletion of CD4(+), but not CD8(+), T cells. Furthermore, the conserved RSV-A G protein cysteines and residues 193 and 194, overlapping the recently identified T helper cell epitope on the G protein (P. W. Tebbey et al., J. Exp. Med. 188:1967-1972, 1998), were found to be essential for URT but not LRT protection. Taken together, these results demonstrate for the first time that CD4(+) T cells induced upon parenteral immunization with an RSV G protein fragment play a critical role in URT protection of normal mice against RSV infection.

Adoptive Transfer↗