Neutropenia as an adverse event following vaccination : results from randomized clinical trials in healthy adults and systematic review

Background : In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology : We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings : Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions : It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events

Booster Vaccination With GVGH Shigella sonnei 1790GAHB GMMA Vaccine Compared to Single Vaccination in Unvaccinated Healthy European Adults: Results From a Phase 1 Clinical Trial

The investigational Shigella sonnei vaccine (1790GAHB) based on GMMA (generalized modules for membrane antigens) is immunogenic, with an acceptable safety profile in adults. However, pre-vaccination anti-S. sonnei lipopolysaccharide (LPS) antibody levels seemed to impact vaccine-related immune responses. This phase 1, open-label, non-randomized extension study (ClinicalTrials.gov: NCT03089879) evaluated immunogenicity of a 1790GAHB booster dose in seven adults with undetectable antibodies prior to priming with three 1790GAHB vaccinations 2–3 years earlier (boosted group), compared to one dose in 28 vaccine-naïve individuals (vaccine-naïve group). Anti-S. sonnei LPS serum IgG geometric mean concentrations and seroresponse (increase of ≥25 EU or ≥50% from baseline antibody ≤ 50 EU and ≥50 EU, respectively) rates were calculated at vaccination (day [D]1), D8, D15, D29, D85. Safety was assessed. Geometric mean concentrations at D8 were 168 EU (boosted group) and 32 EU (vaccine-naïve group). Response peaked at D15 (883 EU) and D29 (100 EU) for the boosted and vaccine-naïve groups. Seroresponse rates at D8 were 86% (boosted group) and 24% (vaccine-naïve group) and increased at subsequent time points. Across both groups, pain (local) and fatigue (systemic) were the most frequent solicited adverse events (AEs). Unsolicited AEs were reported by 57% of boosted and 25% of vaccine-naïve participants. No deaths, serious AEs, or AEs of special interest (except one mild neutropenia case, possibly vaccination-related) were reported. One 1790GAHB dose induced a significant booster response in previously-primed adults, regardless of priming dose, and strong immune response in vaccine-naïve individuals. Vaccination was well tolerated

Literature Review and Case Histories of Histoplasma capsulatum var. duboisii Infections in HIV-infected Patients

African histoplasmosis during HIV infection is rare

Vaccins pandémiques et prépandémiques dirigés contre le virus grippal H5N1

Depuis 1997, plusieurs centaines de cas d’infection par le virus grippal aviaire H5N1 ont été rapportées chez l’homme avec un taux de létalité d’environ 60 %, faisant redouter une pandémie grippale dans une population sans immunité préalable. Actuellement, la transmission interhumaine reste limitée à des personnes en contact étroit avec les volailles. En prévision de cette menace pandémique, un plan mondial a été mis en place dans lequel la vaccination représente un élément majeur. Cependant, la mise au point d’un vaccin pose de nombreux problèmes comme la manipulation des souches et l’évaluation de l’immunogénicité. En outre, les délais de production après l’identification du virus pandémique sont incompressibles et la pandémie risquerait de se développer avant qu’un vaccin soit disponible. Des approches ont donc été développées pour produire des vaccins pré-pandémiques capables d’induire une immunité croisée, partiellement efficace sur la souche pandémique. En 2009, plusieurs vaccins pré-pandémiques et pandémiques ont obtenu leur autorisation de mise sur le marché et des stratégies d’utilisation sont développées dans l’hypothèse de l’émergence d’une pandémie

Surexpression de la protéine A par le phage phi SLT dans des souches de Staphylococcus aureus productrices de leucocidine de Panton Valentine

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF