Novel combination therapy for the eradication of Helicobacter pylori infection in a mouse model.

OBJECTIVE: To investigate the combination therapy, consisting of hyperimmune bovine colostrum, N-acetyl cysteine, zinc and amoxicillin on the eradication of Helicobacter pylori in a mouse model. MATERIAL AND METHODS: C57BL/6 female mice (6 weeks of age) were inoculated with 0.1 ml of 1×10(9) H. pylori via a single oro-gastric gavage and were left infected for 4 weeks. Mice (n=9/group) were randomly allocated to receive by oral gavage (0.1 ml) HNZ (hyperimmune bovine colostrum+N-acetyl cysteine+zinc), HNZA (HNZ+amoxicillin; A), HNZA2 (2× amoxicillin; A2), HNZA5 (5× amoxicillin; A5), triple therapy (TT) or saline twice daily for 10 days. Bacterial load was assessed by culture. Gastric emptying was assessed by 13C-octanoic acid breath test. RESULTS: Mice receiving HNZ, HNZA, and HNZA2 have a 22%, 44% and 67% eradication rate, respectively. Eradication rate was 100% with HNZA5, TT and those animals receiving A5 alone. In H. pylori infected mice there was an increased gastric emptying time by 7.9, 3.7, 10.1 and 7.7 min for the TT, HNZ, HNZA2, and HNZA5, respectively, compared to saline. CONCLUSIONS: HNZ with the addition of a high dose of amoxicillin is effective at eradicating H. pylori in vivo as HNZA1 and HNZA2 did not give raise to eradication. The potency of the novel anti-H. pylori combination therapy may be due to the delayed gastric emptying.

Meningococcal serogroup B-specific responses after vaccination with bivalent rLP2086: 4 year follow-up of a randomised, single-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Bivalent rLP2086 is a recombinant factor H binding protein-based vaccine approved in the USA for prevention of meningococcal serogroup B disease in 10-25-year-olds. We aimed to assess the persistence of bactericidal antibodies up to 4 years after a three-dose schedule of bivalent rLP2086. METHODS: We did this randomised, single-blind, placebo-controlled, phase 2 trial at 25 sites in Australia, Poland, and Spain. In stage 1 of the study (February, 2009-May, 2010), healthy adolescents (aged 11-18 years) were randomly assigned, via an interactive voice and web-response system with computer-generated sequential random numbers, to receive either ascending doses of vaccine (60 µg, 120 µg, and 200 µg) or placebo at months 0, 2, and 6. Dispensing staff were not masked to group allocation, but allocation was concealed from principal investigators, participants and their guardians, and laboratory personnel. In stage 2 of the study (reported here), we enrolled healthy adolescents who had received three doses of 120 µg bivalent rLP2086 (the optimum dose level identified in stage 1) or saline. Immunogenicity was determined in serum bactericidal antibody assay using human complement (hSBA) by use of four meningococcal serogroup B test strains expressing vaccine-heterologous factor H binding protein variants: PMB80 (A22), PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44). Immunogenicity in stage 2 was assessed at months 6, 12, 24, and 48 post-vaccination. We did analysis by intention to treat. This trial is registered as ClinicalTrials.gov number NCT00808028. FINDINGS: Between March 17, 2010, and Feb 8, 2011, 170 participants who received 120 µg of bivalent rLP2086 and 80 participants who received placebo in stage 1 of the study were entered into stage 2; 210 participants completed stage 2 up to 48 months. 1 month after the third vaccination, 93% (n=139/149) to 100% (n=48/48) of vaccine recipients achieved protective hSBA titres equal to or greater than the lower limit of quantification to each test strain, compared with 0% (n=0/25) to 35% (n=8/23) of control recipients. Despite initial declines in seroprotective hSBA titres for all four test strains, for three test strains (A22, A56, and B24), more than 50% of bivalent rLP2086 recipients continued to achieve titres equal to or greater than the lower limit of quantification at months 6 (57% [n=93/163] to 89% [n=42/47]), 12 (54% [n=84/155] to 69% [n=33/48]), 24 (53% [n=26/49] to 54% [n=82/152]), and 48 (51% [n=24/47] to 59% [n=79/134]); corresponding values in the control group were 14% (n=11/80) to 22% (n=5/23) at month 6, 13% (n=10/78) to 29% (n=22/76) at month 12, 16% (n=12/74) to 36% (n=8/22) at month 24, and 24% (n=16/68) to 35% (n=8/23) at month 48. For test strain B44, hSBA titres equal to or greater than the lower limit of quantification were shown in 37% (n=18/49) of vaccine recipients at 6 months, in 29% (n=14/48) at 12 months, in 22% (n=11/49) at 24 months, and in 20% (n=10/49) at 48 months, compared with 0% (n=0/25) of control recipients at month 6, 4% (n=1/25) at months 12 and 24, and 12% (n=3/25) at month 48. Adverse events were reported in seven (4%) of 170 participants in the bivalent rLP2086 group and two (3%) of 80 participants in the control group; no event was deemed related to vaccine. INTERPRETATION: After three doses of bivalent rLP2086, protective hSBA titres above the correlate of protection (≥1/4) were elicited up to 4 years in more than 50% of participants for three of four meningococcal serogroup B test strains representative of disease-causing meningococci expressing vaccine-heterologous antigens. Further studies will be needed to assess possible herd immunity effects with meningococcal serogroup B vaccines and the need for a booster dose to sustain individual protection against invasive meningococcal disease. FUNDING: Pfizer.

Recurrence of extensive injection site reactions following DTPa or dTpa vaccine in children 4-6 years old.

OBJECTIVES: The aim of this study was to compare the immunogenicity and reactogenicity of a lower dose diphtheria, tetanus and pertussis vaccine (dTpa) with the recommended vaccine (DTPa) given as a fifth dose to 4-6-year old children who previously experienced an extensive injection site reaction (ISR). MATERIAL AND METHODS: Children aged 4-6 years who had experienced an extensive ISR following a 4th dose of DTPa were recruited and randomly assigned to receive either the recommended DTPa or the lower dose dTpa vaccine. Parents recorded local reactions and systemic events for 15 days following vaccination. Immunogenicity was assessed pre and post vaccination by ELISA for diphtheria (D), tetanus (T), pertussis toxin (PT), filamentous haemagglutinin (FHA), and pertactin (PRN). RESULTS: A total of 53 participants were vaccinated. There was a 72% recurrence rate of ISR, with a trend (p=0.055) towards fewer ISR in the dTpa (61.5%) compared with the DTPa group (85.2%). There was no difference in reports of pain or irritability between groups. All participants had seroprotective levels of antibody to D and T and seroresponse to each of the 3 pertussis antigens following vaccination with higher GMCs in DTPa vs dTpa group. There was no increase in antibody avidity observed post vaccination, regardless of vaccine given. CONCLUSION: Recurrence of ISR with the 5th dose of diphtheria, tetanus and pertussis vaccination in children who have previously experienced an extensive ISR is high. Vaccination with a dTpa vaccine may reduce the risk of fifth dose ISR.