Explore the vast range of titles available.

In this trial, obinutuzumab, a humanized type II anti-CD20 monoclonal antibody, plus standard therapy provided significantly better renal responses than standard therapy alone in patients with lupus nephritis.

•Pentavalent reassortant rotavirus vaccine was tested for efficacy in infants.•The vaccine (BRV-PV) showed excellent tolerability and a good safety profile.•Primary analysis efficacy was 36% against SRVGE and up to 60.5% against VSRVGE.•The efficacy through 2years of age was 39.5% (SRVGE) and 54.7% (VSRVGE).•The intent to treat analyses confirmed all the per protocol analyses. Rotavirus is the most common cause of moderate-to-severe infant diarrhoea in developing countries, resulting in enormous morbidity, mortality, and economic burden. A bovine-human reassortant pentavalent rotavirus vaccine (BRV-PV) targeting the globally most common strains was developed in India and tested in a randomized, double-blind, placebo-controlled end-point driven Phase III efficacy clinical trial implemented at six sites across India. Infants 6 to 8weeks of age were randomized (1:1) to receive three oral doses of BRV-PV or placebo at 6, 10, and 14weeks of age along with routine vaccines. Home visit surveillance was conducted to detect severe rotavirus gastroenteritis (SRVGE) and safety outcomes until the children reached two years of age. A total of 3749 infants received BRV-PV while 3751 received placebo. At the time of the primary end-point (when the minimum number of cases needed for analysis were accrued) the vaccine efficacy against SRVGE was 36% (95% CI 11.7, 53.6, p=0.0067) in the per protocol (PP) analysis, and 41.9% (95% CI 21.1, 57.3, p=0.0005) in the intent to treat (ITT) analysis. Vaccine efficacy over the entire follow-up period (until children reached two years of age) was 39.5% (95% CI 26.7, 50, p<0.0001) in the PP analysis and 38.8% (95% CI, 26.4, 49, p<0.0001) in the ITT analysis. Vaccine efficacy against the very severe rotavirus cases (VSRVGE, Vesikari score≥16) was 60.5% (95% CI 17.7, 81, p=0.0131) at the time of the primary analysis and 54.7% (95% CI 29.7, 70.8, p=0.0004) for the complete follow-period in the PP population. The incidence of solicited, unsolicited, and serious adverse events were similar in both the vaccine and placebo groups. Likewise, the number of intussusceptions and deaths were similar between both groups. Thus, BRV-PV is an effective, well tolerated and safe vaccine in Indian infants. (Trial registration: Clinical Trials.Gov [NCT 02133690] and Clinical Trial Registry of India [CTRI/2013/05/003667]).

Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers. Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated. Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations. ClinicalTrials.gov NCT01168401.

Fe supplementation is a common strategy to correct Fe-deficiency anaemia in children; however, it may modify the gut microbiota and increase the risk for enteropathogenic infection. In the present study, we studied the impact of Fe supplementation on the abundance of dominant bacterial groups in the gut, faecal SCFA concentration and gut inflammation in children living in rural South Africa. In a randomised, placebo-controlled intervention trial of 38 weeks, 6- to 11-year-old children with Fe deficiency received orally either tablets containing 50 mg Fe as FeSO4 (n 22) for 4 d/week or identical placebo (n 27). In addition, Fe-sufficient children (n 24) were included as a non-treated reference group. Faecal samples were analysed at baseline and at 2, 12 and 38 weeks to determine the effects of Fe supplementation on ten bacterial groups in the gut (quantitative PCR), faecal SCFA concentration (HPLC) and gut inflammation (faecal calprotectin concentration). At baseline, concentrations of bacterial groups in the gut, faecal SCFA and faecal calprotectin did not differ between Fe-deficient and Fe-sufficient children. Fe supplementation significantly improved Fe status in Fe-deficient children and did not significantly increase faecal calprotectin concentration. Moreover, no significant effect of Fe treatment or time × treatment interaction on the concentrations of bacterial groups in the gut or faecal SCFA was observed compared with the placebo treatment. Also, there were no significant differences observed in the concentrations of any of the bacterial target groups or faecal SCFA at 2, 12 or 38 weeks between the three groups of children when correcting for baseline values. The present study suggests that in African children with a low enteropathogen burden, Fe status and dietary Fe supplementation did not significantly affect the dominant bacterial groups in the gut, faecal SCFA concentration or gut inflammation.

•A randomized, double-blind, placebo-controlled trial was conducted in healthy Chinese infants.•Efficacy and safety of a pentavalent rotavirus vaccine (RV5) were assessed.•Efficacy against rotavirus gastroenteritis of any-severity caused by any serotype was 69.3%.•Efficacy against severe rotavirus gastroenteritis caused by any serotype was 78.9%.•RV5 was efficacious and generally well-tolerated in Chinese infants. A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). 4040 participants aged 6–12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.

Noroviruses are the leading cause of epidemic acute gastroenteritis and foodborne diarrheal disease in humans. Here, a randomized, double-blind, multi-cohort, placebo-controlled clinical trial was performed to determine the candidate vaccine's safety and immunogenicity. The experimental framework incorporated an initial Phase I age/dose-escalation stage followed by a Phase IIa dose-expansion component. A total of 580 participants (five groups: 6 weeks to 23 months, 2-5 years, 6-17 years, 18-59 years, and ≥60 years) were randomized into 13 groups to receive intramuscular injections of either a placebo (aluminium-containing or aluminium-free) or vaccine formulation (low-dose or high-dose) on days 0, 30 and 60. The safety outcomes included the incidence of all adverse events within 0-30 days post-vaccination and all serious adverse events within 6 months. Immunogenicity analyses focused on seroconversion rates against four norovirus genotypes (GI.1, GII.3, GII.4, GII.17) at 30 days post-third vaccination, including IgA, IgG and histoblood group antigen (HBGA)-blocking antibodies (BT50). The results of the Phase I and Phase IIa clinical trials indicated that the IgA seroconversion rates against the four norovirus genotypes at 30 days post-third vaccination were 49.45-86.81% in the low-dose group versus 66.12-85.25% in the high-dose group. IgG seroconversion ranged from 63.74% to 93.41% (low-dose) and 72.13% to 92.35% (high-dose), while HBGA-blocking antibody responses ranged from 64.84-86.26% (low-dose) and 78.14-89.62% (high-dose). Adverse reactions predominantly occurred within 0-7 days post-vaccination, with Grade 1-2 events predominating. The most frequent reactions included injection-site pain and fever. This trial is registered at www.chictr.org.cn (ChiCTR2400089762).

A phase III, randomized, double-blind study evaluated the efficacy, reactogenicity, safety and immunogenicity of a human rotavirus vaccine, RIX4414 in Japanese infants aged 6–14 weeks when administered as two doses (0, 1-month schedule). Efficacy against any and severe rotavirus gastroenteritis leading to medical intervention caused by circulating wild-type rotavirus from two weeks post-Dose 2 until two years of age was 79.3% (95% CI: 60.5–89.8%) and 91.6% (95% CI: 62.4–99.1%), respectively. Solicited, unsolicited symptoms and serious adverse events were reported at a similar frequency in both groups. Serum anti-rotavirus antibody seroconversion rate one-month post-Dose 2 was 85.3% (95% CI: 68.9–95%) in RIXX4414 group. RIX4414 was efficacious, well-tolerated and immunogenic in Japanese infants and introduction of vaccination could help in reducing the disease burden.

A pentavalent human–bovine reassortant oral rotavirus vaccine, RotaTeq ®, was evaluated among nearly 70,000 infants in the Rotavirus Efficacy and Safety Trial (REST), of which 30,523 were from Europe. All infants were followed for serious adverse events as well as hospitalizations and emergency department (ED) visits. All adverse events, health care utilization, and RVGE regardless of severity were evaluated in the clinical efficacy cohort ( N = 2686) in Finland. RotaTeq ® was 98.3% (95% CI, 90.2–100%) and 68.0% (95% CI 60.3–74.4%) efficacious against severe rotavirus gastroenteritis (RVGE) and all RVGE due to any serotype for two rotavirus seasons post-vaccination. The combined rate of hospitalizations and ED visits due to RVGE of any serotype was reduced by 94.5% (95% CI, 91.3–96.8%) for up to 2 years after vaccination. There were no statistically significant differences between RotaTeq ® and placebo for any of the safety outcomes. In Europe, RotaTeq ® was highly efficacious and well tolerated.

Background. Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at ≥90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age. Methods. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months. Results. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype. Conclusions. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.

Transmissible gastroenteritis coronavirus (TGEV) is a member of the genus Coronavirus , family Coronaviridae, order Nidovirales. TGEV is an enteropathogenic coronavirus that causes highly fatal acute diarrhoea in newborn pigs. An oral Lactobacillus casei ( L. casei ) vaccine against anti-transmissible gastroenteritis virus developed in our laboratory was used to study mucosal immune responses. In this L. casei vaccine, repetitive peptides expressed by L. casei (specifically the MDP and tuftsin fusion protein (MT)) were repeated 20 times and the D antigenic site of the TGEV spike (S) protein was repeated 6 times. Immunization with recombinant Lactobacillus is crucial for investigations of the effect of immunization, such as the first immunization time and dose. The first immunization is more important than the last immunization in the series. The recombinant Lactobacillus elicited specific systemic and mucosal immune responses. Recombinant L. casei had a strong potentiating effect on the cellular immunity induced by the oral L. casei vaccine. However, during TGEV infection, the systemic and local immune responses switched from Th1 to Th2-based immune responses. The systemic humoral immune response was stronger than the cellular immune response after TGEV infection. We found that the recombinant Lactobacillu s stimulated IL-17 expression in both the systemic and mucosal immune responses against TGEV infection. Furthermore, the Lactobacillus vaccine stimulated an anti-TGEV infection Th17 pathway. The histopathological examination showed tremendous potential for recombinant Lactobacillus to enable rapid and effective treatment for TGEV with an intestinal tropism in piglets. The TGEV immune protection was primarily dependent on mucosal immunity.