Human Neonatal Rotavirus Vaccine (RV3-BB)
WAidid suggests this week an article publisched last month on NEJM and entitled "Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth"
SUMMARY:Despite evidence of the success of rotavirus vaccines, more than 90 million infants still lack access to a rotavirus vaccine. Barriers to global implementation of the vaccine include cost, and suboptimal efficacy in safety concerns. An oral rotavirus vaccine, administered at birth, has the potential to address some of these challenges and could provide early protection and maximize the opportunity to complete a full vaccine schedule. The oral human neonatal rotavirus vaccine (RV3-BB) was developed from the human neonatal rotavirus strain RV3, which was identified in the stool of infants with asymptomatic infection. The authors reported the results of a phase 2b, randomized, double-blind, placebo-controlled trial, involving 1649 participants, conducted from January 2013 through July 2016, in primary health centers and hospitals in Central Java and Yogyakarta, Indonesia. Infants were eligible if they were healthy, full-term babies 0 to 5 days of age, who had a birth weight of 2.5 to 4.0 kg. Eligible infants were randomly assigned, in a 1:1:1 ratio, to one of three groups: a neonatal schedule vaccine group, an infant-schedule vaccine group, or a placebo group. Participants received four 1-ml oral doses of vaccine or placebo according to their trial-group assignment. Each of the two vaccine groups received three doses of RV3-BB and one dose of placebo. Vaccine response, as evidenced by serum immune response (serum rotavirus IgA and neutralizing antibody titers) or shedding of RV3-BB in the stool, was assessed in the first cohort recruited (282 participants). Of the 1649 newborns, who underwent randomization (intention-to-treat population), 1640 received at least one dose of vaccine or placebo (safety population) and 1588 (96%) were followed until they were 18 months of age. In the per-protocol population, severe rotavirus gastroenteritis was reported in 28 of the 504 participants (5.6%) in the placebo group, as compared with 21 of the 1009 participants (2.1%) in the combined vaccine group, resulting in a vaccine efficacy of 63% at 18 months of age (P<0.001). Similar results were observed in the intention-to-treat analysis (P<0.001). When three doses of RV3-BB were administered, according to the neonatal schedule, the vaccine efficacy against severe rotavirus gastroenteritis was 75% (P<0.001) at 18 months of age and 94% (P = 0.006) at 12 months of age. The vaccine efficacy against rotavirus gastroenteritis of any severity in the neonatal-schedule vaccine group at 18 months of age was 63% (P<0.001), while in the infant-schedule vaccine group was 51% (P = 0.03) at 18 months of age and 77% (P = 0.008) at 12 months of age. The vaccine efficacy against rotavirus gastroenteritis of any severity at 18 months of age, when RV3-BB was administered according to the infant schedule, was 45% (P = 0.01). The time from randomization to the first episode of severe rotavirus gastroenteritis was significantly longer among the participants who received RV3-BB than among those who received placebo. Cumulative vaccine response was detected in 78 of 83 participants (94%) in the neonatal-schedule vaccine group and in 83 of 84 participants (99%) in the infant-schedule vaccine group. The difference in the proportion of participants, who had a cumulative vaccine response between the neonatal-schedule vaccine group or the infant-schedule vaccine groups and their corresponding placebo groups, was 0.52 (P<0.001). The incidence of serious adverse events and unsolicited and solicited adverse events was similar across the trial groups. No episodes of intussusception were reported within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule vaccine group. The authors concluded that their data showed that the human neonatal vaccine RV3-BB provided protection against severe rotavirus gastroenteritis, but they highlighted that, despite the success of rotavirus vaccines, challenges to global implementation remain.
AUTHORS: Bines JE, At Thobari J, Satria CD, Handley A, Watts E, Cowley D, Nirwati H, Ackland J, Standish J, Justice F, Byars G, Lee KJ, Barnes GL, Bachtiar NS, Viska Icanervilia A, Boniface K, Bogdanovic-Sakran N, Pavlic D, Bishop RF, Kirkwood CD, Buttery JP, Soenarto Y.
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H-pylori cagA+ and milder duodenal histological changes
This week we suggest an article published in August 2017 on Frontiers in cellular and infection microbiology, Helicobacter pylori cagA+ is associated with milder duodenal histological changes in Chilean celiac patients. You can find the full article here.
SUMMARY:Celiac disease (CD) is an immune-mediated systemic disorder, triggered by ingested gluten and related prolamines in genetically susceptible individuals. CD has progressively increased in prevalence and is associated with significant morbidity, impacting quality of life and health care costs. Overall prevalence is nearly 1%; in Chile, the prevalence of anti-transglutaminase (tTG) antibodies detection, in individuals older than 15 years of age, is 0.8%.The intestinal microbiota is currently under intense evaluation as a potentially relevant pathogenic factor in CD. Helicobacter pylori (H. pylori), a Gram negative spiral bacterium capable of infecting human gastric mucosa, has also been isolated from the duodenum. There is evidence that H. pylori is associated with an increased regulatory T cell response in blood and gastric mucosa, with higher number of Foxp3+ T cells and higher expression of Foxp3 and TGF-b mRNA/protein and a protective role against atopy. Particularly, CagA, a pleomorphic virulence factor of H. pylori, involved in oncogenesis and epithelial barrier disfunction, has also been involved in T-reg pathway activation, and some studies have supposed a modulator role in CD.The authors reported the results of a multicenter, prospective study, performed in Santiago (Chile), in which, between January 2013 and July 2015, a total of 116 patients (1 to 50 years of age) were enrolled: 66 with CD and 50 non-CD. The diagnosis of CD was determined through the anti-tTG, upper gastrointestinal endoscopy and HLA typing. Patients were classified in three groups: active-CD, potential-CD and non-CD patients.A trend toward higher frequency of DQ2/DQ2 and DQ2/DQ8 haplotypes, the presence of abdominal distension and steatorrhea were observed in the active-CD group, compared to potential-CD individuals. Female gender was more frequent, and anti-tTG titers were higher in active-CD, compared to potential-CD patients.Overall H. pylori infection rates were similar between subjects with and without CD, and were independent of the severity of duodenal atrophy in the latter. However, in individuals infected by H. pylori, detection of cagA+ strains was significantly more common among individuals with potential-CD compared to active-CD and non-CD patients (p = 0.02). Among infected subjects, the presence of cagA+ strains was significantly associated with milder histological damage.Overall histological gastritis was more common in non-CD subjects infected with H. pylori, compared to non-infected patients (p = 0.003); however, there was only a trend toward increased gastritis in H. pylori positive individuals in the potential-CD (p = 0.069) and active-CD groups (p = 0.091). There was no association between histological gastritis and cagA+ strains. In patients with active-CD, infected with H. pylori cagA+, the number of Foxp3 positive cells was significantly higher, compared to all the other active-CD groups, as well as to potential-CD subjects infected by cagA+ H. pylori (p < 0.05).TGF-b1 protein concentration, in duodenal biopsies, showed a tendency to be higher in active-CD, compared to potential CD overall (p = 0.19). Individuals infected by cag+ H. pylori strains had lower TGF-b1 levels than non-infected individuals, that was statistically significant in the potential-CD group (p = 0.04).The authors concluded that the similar H. pylori infection rates, among individuals with and without CD, and the association between cagA+ strains and milder histological damage in celiac patients, infected by H. pylori, and in active-CD cases could suggest that infection by cagA+ H. pylori may be protective for CD progression, or conversely, that these strains are prone to colonize when intestinal damage is less severe.
AUTHORS: Lucero Y, Oyarzún A, O'Ryan M, Quera R, Espinosa N, Valenzuela R, Simian D, Alcalde E, Arce C, Farfán MJ, Vergara AF, Gajardo I, Mendez J, Carrasco J, Errázuriz G, Gonzalez M, Ossa JC, Maiza E, Perez-Bravo F, Castro M, Araya M.