Immunomonitoring of human responses to the rVSV-ZEBOV Ebola vaccine

The rVSV-ZEBOV vaccine is currently the only Ebola vaccine with demonstrated clinical efficacy in a ring-vaccination clinical trial. It has been shown to be reactogenic but immunogenic and safe in several Phase I clinical studies. However, its mechanisms of protection are unknown and available immunogenicity data are mostly limited to classical serological analysis; it is now of paramount importance to apply cutting-edge technologies, including transcriptomic and metabolomic analyses, and to perform integrative analyses with standard serology and clinical data to comprehensively profile the rVSV-ZEBOV immune signature

The public perception of the value of vaccines - the case of Switzerland

Aim: In this original article, we seek to analyse the environment in which immunisation policies are adopted and, more specifically, the way the public perception of vaccines influences decision-making, by looking more closely at the case of Switzerland. Subjects and methods: Historical and present-day examples of attitudes towards immunisation and specific vaccines, both on the part of the public and of health-care workers, are reviewed. Results: Decision-making with regard to vaccine policy implementation has been and is still most often driven by fear: fear of disease (when perceived as rampant and/or dangerous), but also fear of vaccine-associated adverse events (when the disease is less or no longer "visible”). However, methodology for introducing evidence-based immunisation policies exists and can be used by public health authorities, while vaccination information systems (such as the Swiss InfoVac) have proven their usefulness in providing trustworthy, peer-based knowledge to health-care workers. Conclusion: Only information based on clear, evidence-based data gathered and analysed according to solid methodological criteria coupled with adequate information of health-care workers (and thus patients) can ensure in future the implementation of scientifically coherent, publicly acceptable, and equitable immunisation policie

Immunization with DNA vaccines in early life: Advantages and limitations as compared to conventional vaccines

Conclusion: DNA vaccines favorably compare to conventional vaccines in their unique capacity to induce, in murine models, adult-like antibody, Th1 and CTL responses at a time of yet significant immune immaturity. Immune responses to DNA vaccines are, however, significantly slower than the one induced by adjuvanted subunit or live vaccines. Although they persist for life in mice, preliminary data in non-human adult primates suggest that this could not be the case in higher mammals. The issue of potential tolerance induction will likely not emerge as a critical feature of human neonatal DNA immunization. However, DNA vaccines are unlikely to prove superior to conventional vaccines in their capacity to circumvent the inhibitory influence of maternal antibodies. Thus, the greater perspectives for neonatal DNA immunization could be found in models where the induction of Th1 and CTL responses are of utmost importance. These are essentially infections with intracellular agents responsible for severe/persistent infections upon early exposure and for which no current efficient and safe conventional vaccine exists. Evaluating neonatal DNA immunization strategies against RSV or herpes viruses, tuberculosis or Chlamydiae therefore emerge as sound prioritie

Highly efficient peptide binding and T cell activation by MHC class II molecules of CIITA-transfected cells

Expression of MHC class II, DM and li genes is controlled by the transactivator CIITA, a mediator of the activation of these genes by IFN-γ. Surprisingly, MHC class II molecules expressed on CIITA transfectants behave very differently from those expressed at the same level on lFN-γ-induced cells in terms of peptide binding and peptide-speclfic T cell activation. MHC class II-positive CIITA transfectants exhibit an unusually high capacity for binding exogenous peptides, with a higher percentage of DR molecules occupied by a given peptide and are much more efficient at peptide specific, HLA-DR-restricted activation of T lymphocytes. This unexpected phenotype reflects the antigen processing defect observed in CIITA transfectants. It suggests novel strategies for the use of CIITA-transformed cells in peptide-based immunizatio

The two novel MHC class II transactivators RFX5 and CIITA both control expression of HLA-DM genes

MHC-encoded HLA-DMA and-DMB molecules are atypical MHC chains that play an essential role in antigen presentation by MHC class II molecules. They resemble both MHC class I and II molecules but are not expressed at the cell surface. From the study of MHC class II regulatory mutants, it was found recently that two novel transactivators, CIITA and RFX5, are essential for the control of MHC class II gene expression. We report here that CIITA and RFX5, although operating at different levels of transcriptional control, are also both essential regulators of HLA-DMA and-DMB genes. This is true for both the constitutive and the inducible mode of DM gene expression. Indeed, both CIITA and RFX5 cDNA can correct the HLA-DMA and-DMB gene expression defect in the respective regulatory mutants. The involvement of these two transcription factors accounts for the coordinate expression of MHC class II and HLA-DM, two sets of molecules that perform quite different functions in the overall process of antigen presentatio

Nasopharyngeal Carriage of Streptococcus pneumoniae Shortly before Vaccination with a Pneumococcal Conjugate Vaccine Causes Serotype-Specific Hyporesponsiveness in Early Infancy

Background. The antibody response to pneumococcal conjugate vaccines (PCVs) in infants is variable. Factors responsible for this variability have not been fully elucidated. The objective of this study was to investigate whether pneumococcal carriage around the time of the first dose of 7-valent PCV (PCV7) affects serotype-specific immunologic response. Methods. Healthy 2-month old infants were randomized to receive 2 (at the ages of 4 and 6 months) or 3 (at the ages of 2, 4, and 6 months) PCV7 doses and a booster dose (at the age of 12 months). Nasopharyngeal or oropharyngeal specimens were obtained for culture shortly before the first PCV7 dose. Serotype-specific immunoglobulin (Ig) G levels were measured at ages 2, 7, and 13 months. Results. Of 545 children studied, 332 received a booster dose. The most common serotypes carried around the time of the first PCV7 dose were 6B (n = 37), 19F (n = 22), and 23F (n = 14). In carriers before the first dose, the IgG response to the carried serotype after 2 or 3 doses was significantly lower than in noncarriers. In contrast, response to the noncarried serotypes was not affected. Although all children responded to the booster dose, the response to the originally carried serotype was generally lower. Conclusions. Serotype-specific hyporesponsiveness to PCV7 after pneumococcal carriage in infants is demonstrated for the first time. This phenomenon was common, lasted for at least several months, and was only partially overcome by the 12-month booster. Trial registration. isrctn.org identifier: ISRCTN2844584

Influenza Immunization: Improving Compliance of Healthcare Workers

OBJECTIVE: In spite of yearly recalls, influenza immunization rates of healthcare workers (HCWs) remained low (10%) at the University Hospitals of Geneva. This study was conducted to identify HCWs' reasons for rejection of immunization, to design specific intervention methods based on these reasons, and to evaluate the impact of such interventions. METHODS: Three departments with high-risk patients (geriatrics, obstetrics, and pediatrics) were selected as main targets. Questionnaires were distributed in these units. Based on HCWs' perceptions, different intervention methods were designed and used either in these departments only (educational conferences, on-site availability of a vaccination nurse) or in the whole institution (posters, personal letters). Immunization rates were collected throughout the institution. RESULTS: 797 completed questionnaires from 1,092 HCWs (73%) were returned. Major reasons for immunization rejection were confidence that their bodies' self-defense mechanisms would ward off infection (32%), perception of low exposure risk (23%), and doubts concerning vaccine efficacy (19%). The use of intervention methods designed to address these factors increased influenza immunization rates in the three targeted departments from 13% (95% confidence interval [CI95], 11.4-15.6) in 1995 and 1996 to 37% (CI95, 34.5-40.3) in the following season (P<.001). In all other departments, immunization rates rose from 9% (CI95, 8.5-10.3) to 23%% (CI95, 21.6-24.1; P<.001). Nurses were, and remained, more reluctant to be immunized compared to other HCWs. CONCLUSIONS: Influenza immunization rates can be increased significantly by specific interventions based on local concerns of HCWs, among which educational conferences and the on-site availability of a vaccination nurse appeared importan

Response to Treatment and Disease Progression Linked to CD4+ T Cell Surface CC Chemokine Receptor 5 Density in Human Immunodeficiency Virus Type 1 Vertical Infection

The factors governing interindividual variability in disease progression among children vertically infected with human immunodeficiency virus type 1 (HIV-1) remain unclear. Because it has recently been shown in infected adults that the density of CC chemokine receptor 5 (CCR5) molecules at the surface of nonactivated (human leukocyte antigen [HLA]-DR-) CD4+ T cells correlates with disease progression, the same correlation was sought in children. HLA-DR-CD4+ T cell surface CCR5 density was constant over time and correlated with the bioclinical stage and with the CD4 cell slope observed before antiretroviral treatment. In addition, CCR5 density was negatively correlated with the intensity of the decrease in viremia during antiretroviral therapy and was positively correlated with CD4 cell slope since birth. These results are compatible with the hypothesis that CCR5 density is a key factor governing disease progression in pediatric HIV-1 infection and, thereby, an indicator of prognosis. Moreover, they suggest that therapies aimed at reducing CCR5 accessibility should slow down HIV disease evolution in childre

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 ∼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 transmissio