Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.

BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. METHODS: In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. RESULTS: AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. CONCLUSION: AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02014727; PACTR201402000719423.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection.

OBJECTIVES: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. METHODS: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. RESULTS: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. CONCLUSION: PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.

[Consequences for the family of a very preterm birth two months after discharge. Results of the EPIPAGE qualitative study]. / Conséquences pour la famille d'une naissance très prématurée deux mois après le retour à la maison. Résultats de l'enquête qualitative d'EPIPAGE.

OBJECTIVES: To assess mothers' and fathers' psychological health 2 months after discharge of a very preterm infant. To describe the problems encountered with the child, the quality of the marital relationship, the organization of the family and to compare the answers made by mothers and fathers. POPULATION: Mothers having delivered before 33 weeks in two maternity units in Paris and in Rouen were contacted. Among the 38 mothers who were eligible, 21 accepted to participate. Their children were born between 26 weeks and 32 weeks and weighted from 630 to 2100 g. METHOD: A semi-structured interview was conducted at home by a psychologist with each member of the couple. It lasted approximately 1 h. Each interview was tape-recorded and fully transcribed. The analysis allowed to discover the main themes emerging from the interviews and to search for the role of factors. RESULTS: Two months after discharge, mothers expressed anxiety and feelings of depression. Fathers noted considerable fatigue and both parents expressed concerns about the child's health and development. Marital dissatisfaction and behavioural symptoms in siblings were also noted. Mothers' difficulties were not linked to the degree of prematurity or length of stay in neonatal unit but with the baby's present health state, his rehospitalizations and maternal characteristics such as isolation, lack of support and previous perinatal loss. The mother's psychological organisation modifies the role of objective factors. Fathers seemed more able to cope with and overcome the traumatic event caused by the very preterm birth. They insisted on their role of support for the mother and the mother-child relationship. CONCLUSION: The consequences of a very preterm birth are important and concern the whole family. After hospital discharge, the follow-up care of the very preterm baby should take the family social and psychological situation into account.