Food products containing angiotensin converting enzyme (ACE) inhibitory peptides reportedly play a role in treatment of mild hypertension. The aim of this placebo-controlled crossover study was to assess the bioavailability of Ile-Pro-Pro and 7 other ACE-inhibiting peptides present in a lactotripeptide (LTP)-enriched yogurt beverage and whether meal intake affects Ile-Pro-Pro bioavailability. Six male and female subjects randomly consumed an LTP-enriched yogurt beverage or a placebo in the fasted state and an LTP-enriched yogurt beverage in the fed or fasted state. The area under the curve (AUC) of Ile-Pro-Pro after the LTP treatment in the fasted state was 2.1-fold of that after the placebo treatment (P < 0.001). The maximum peptide plasma concentration (C(max)) value was greater after consumption of the LTP-enriched beverage (897 +/- 157 pmol/L) than after the placebo treatment (555 +/- 0.09 pmol/L; P < 0.001) with a greater time after ingestion when reaching C(max) (T(max)) in the placebo treatment. Plasma concentrations of the peptides Leu-Trp, Phe-Tyr, Ile-Tyr, and Leu-Pro-Pro increased compared with baseline (P < 0.05) in the LTP-enriched and placebo treatment when consumed in the fasted state. However, DeltaC(max) values differed significantly between the placebo and LTP-enriched treatment only for Leu-Pro-Pro. Meal intake affected Ile-Pro-Pro concentrations. When the beverage was consumed after a meal, the AUC of Ile-Pro-Pro was 1.3-fold (P < 0.05) of the AUC derived from premeal intake. This was due to an increase in the plasma elimination half-life (P < 0.05); C(max) and T(max) were not affected by meal intake. In summary, this is the first demonstration, to our knowledge, that the tripeptide Ile-Pro-Pro selectively escapes from intestinal degradation and reaches the circulation undegraded.
The highest incidence of invasive meningococcal disease is in young children, with a second peak in adolescents/young adults. All five major disease-causing serogroups (A, B, C, W-135 and Y) have been described in Asia. Immunogenicity and safety of the investigational meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT, GlaxoSmithKline Biologicals) was evaluated in healthy, meningococcal conjugate vaccine-naïve adolescents in the Philippines, India and Taiwan. 1025 adolescents were randomized (3:1) to receive one dose of ACWY-TT or tetravalent ACWY polysaccharide vaccine (Mencevax™, Men-PS). Serum bactericidal activity using rabbit complement (rSBA) was measured. Local and systemic adverse reactions were recorded for 4 days. Safety data were pooled with results from a second, similarly designed study in adults for evaluation of grade 3 systemic events. The pre-specified immunogenicity criterion for non-inferiority to Men-PS was met. One month post-vaccination, ≥85.4%-97.1% had a vaccine response (post-titre ≥1:8 in initially seronegative and ≥4-fold increase in seropositive), versus 78.0%-96.6% after Men-PS, against each vaccine serogroup. Exploratory comparisons showed statistically significantly higher post-vaccination rSBA geometric mean titres against all serogroups following ACWY-TT versus Men-PS. Exploratory analysis showed no statistically significant differences between groups in grade 3 general symptoms; however, the statistical criterion for non-inferiority between pooled treatment groups in terms of the ratio of incidences of grade 3 general symptoms was not demonstrated. No SAEs were related to vaccination. ACWY-TT was immunogenic in Asian adolescents with a reactogenicity profile that was clinically acceptable and similar to that of licensed Men-PS. The results of this study indicate that ACWY-TT could be used as a third conjugate vaccine in the protection of adolescents against meningococcal disease.
ACWY-TT was immunogenic in children between 2 to 10 years of age with a clinically acceptable safety profile that resembled licensed Men-PS. These data support a positive benefit/risk ratio for the ACWY-TT vaccine.
Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ≥ 1:32 in initially seronegative; ≥ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ≥ 98.0% of subjects had rSBA titers ≥ 1:128. Grade 3 solicited AEs were reported in ≤ 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults.
This study is registered at clinicaltrials.gov NCT00453986
Effective vaccines offering broad protection to toddlers, who are at high risk for invasive meningococcal disease, are needed. Here, the immunogenicity, safety and antibody persistence of the tetravalent meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in toddlers. Healthy participants aged 12 to 23 mo (n = 304) were randomized (3:1) to receive one dose of MenACWY-TT or a monovalent meningococcal serogroup C conjugate vaccine (MenC-CRM197). Serum bactericidal activity was evaluated with assays using rabbit (rSBA) and human (hSBA) complement up to three years post-vaccination. MenACWY-TT was demonstrated to be non-inferior to MenC-CRM197 in terms of immunogenicity to serogroup C, and the pre-specified immunogenicity criteria for serogroups A, W-135 and Y were met. Exploratory analyses suggested that rSBA geometric mean titers (GMTs), hSBA GMTs and proportions of toddlers with rSBA titers ≥ 1:128 and hSBA titers ≥ 1:4 and ≥ 1:8 were higher for all serogroups at one month post-vaccination with MenACWY-TT compared with MenC-CRM197. At three years post-vaccination, at least 90.8% and 73.6% of MenACWY-TT recipients retained rSBA titers ≥ 1:8 for all serogroups and hSBA titers ≥ 1:4 for serogroups C, W-135 and Y, respectively, but the percentages of toddlers with hSBA titers ≥ 1:4 for serogroup A decreased to 21.8%. In both groups, grade 3 adverse events were infrequently reported and no serious adverse events were considered causally related to vaccination. These results suggest that one single dose of MenACWY-TT induces a robust and persistent immune response and has an acceptable safety profile in toddlers. This study has been registered at www.clinicaltrials.gov NCT00427908.
MenACWY-TT was immunogenic when administered as a single dose at 12 months of age, or as 2 doses at 9 and 12 months, and had a clinically acceptable safety profile. Good antibody persistence was observed through 12 months postvaccination after both treatment schedules for serogroups C, W-135, Y.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.