Dataset Information

Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial.

ABSTRACT: BACKGROUND:Group A streptococcus (GAS) is a serious human pathogen that affects people of different ages and socio-economic levels. Although vaccination is potentially one of the most effective methods to control GAS infection and its sequelae, few prototype vaccines have been investigated in humans. In this study, we report the safety and immunogenicity of a novel acetylated peptide-protein conjugate vaccine candidate MJ8VAX (J8-DT), when delivered intramuscularly to healthy adults. METHODS:A randomized, double-blinded, controlled Phase I clinical trial was conducted in 10 healthy adult participants. Participants were randomized 4:1 to receive the vaccine candidate (N = 8) or placebo (N = 2). A single dose of the vaccine candidate (MJ8VAX), contained 50 ?g of peptide conjugate (J8-DT) adsorbed onto aluminium hydroxide and re-suspended in PBS in a total volume of 0.5 mL. Safety of the vaccine candidate was assessed by monitoring local and systemic adverse reactions following intramuscular administration. The immunogenicity of the vaccine was assessed by measuring the levels of peptide (anti-J8) and toxoid carrier (anti-DT)-specific antibodies in serum samples. RESULTS:No serious adverse events were reported over 12 months of study. A total of 13 adverse events (AEs) were recorded, two of which were assessed to be associated with the vaccine. Both were mild in severity. No local reactogenicity was recorded in any of the participants. MJ8VAX was shown to be immunogenic, with increase in vaccine-specific antibodies in the participants who received the vaccine. The maximum level of vaccine-specific antibodies was detected at 28 days post immunization. The level of these antibodies decreased with time during follow-up. Participants who received the vaccine also had a corresponding increase in anti-DT serum antibodies. CONCLUSIONS:Intramuscular administration of MJ8VAX was demonstrated to be safe and immunogenic. The presence of DT in the vaccine formulation resulted in a boost in the level of anti-DT antibodies. TRIAL REGISTRATION:ACTRN12613000030774.

SUBMITTER: Sekuloski S

PROVIDER: S-EPMC6028081 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial.

Sekuloski Silvana S Batzloff Michael R MR Griffin Paul P Parsonage William W Elliott Suzanne S Hartas Jon J O'Rourke Peter P Marquart Louise L Pandey Manisha M Rubin Fran A FA Carapetis Jonathan J McCarthy James J Good Michael F MF

PloS one 20180702 7

<h4>Background</h4>Group A streptococcus (GAS) is a serious human pathogen that affects people of different ages and socio-economic levels. Although vaccination is potentially one of the most effective methods to control GAS infection and its sequelae, few prototype vaccines have been investigated in humans. In this study, we report the safety and immunogenicity of a novel acetylated peptide-protein conjugate vaccine candidate MJ8VAX (J8-DT), when delivered intramuscularly to healthy adults.<h4> ...[more]

PMID: 29965967

Similar Datasets

Project description:BackgroundAlthough the killed whole-cell and live attenuated plague vaccine have been licensed, they are rarely used today because of toxicities, limited evidence of efficacy against plague, poor immune persistence required booster immunization every year, and limited commercial availability. This study was a randomized phase 2a clinical trial aimed to evaluating the immunogenicity and safety of a novel subunit plague vaccine.Methods240 healthy adults aged 18-55 y were enrolled and randomly assigned at a ratio of 1:1 to receive 2 doses of 15 or 30 mcg vaccine at a 28-day interval between doses. Blood samples were collected at day 0, 28 and 56. Adverse events were collected during the first 28 d after each vaccination. Serious Adverse Event was observed throughout the study period.Results239 participants received the first dose at day 0 and 238 received the second dose at day 28. Antibodies to envelope antigen faction 1 (F1) and recombinant virulence antigen (rV) were increased at day 28, and boosted significantly at day 56. For anti-F1 antibodies, geometric mean titer (GMT) and geometric mean fold increase (GMFI) were significantly higher in 30 mcg group than in the 15 mcg group(each P1< 0.05 at day 28 and each P1< 0.001 at day 56), with similar seroconversion rate of antibodies between 15 and 30 mcg group at both of the 2 time points. For anti-rV antibodies, seroconversion rate at day 28 in 30 mcg group was higher than that in 15 mcg group. However, GMT and GMFI of anti-rV antibodies were increased to approximately the same levels in the 2 groups. Similar booster immune response was also noticed in both groups at day 56. The injections were well tolerated, with mainly mild or moderate local and systemic adverse reactions (lower than grad 3). The proportion of pain at injection site was higher in 30 mcg group. None of SAEs were reported during 56 d.ConclusionThe plague vaccine comprised of F1 and rV antigens showed good safety and immunogenicity in adults aged 18-55 y old. The data show that the 30 mcg formulation is generally more immunogenic than the 15 mcg formulation, and represents the preferred formulation for further clinical development. It will be important to evaluate the long-term efficacy for appropriate formulations of the plague subunit vaccine.

Project description:ImportanceAn alternative option to maternal vaccination to prevent severe pertussis in infants is vaccination at birth. Data are needed on the immunogenicity and safety of a birth dose of monovalent acellular pertussis (aP) vaccine.ObjectiveTo compare IgG antibody responses to vaccine antigens at 6, 10, 24, and 32 weeks of age between newborn infants receiving the aP vaccine and hepatitis B vaccine (HBV) or HBV alone.Design, setting, and participantsA randomized clinical trial was conducted at 4 sites in Australia (Sydney, Melbourne, Adelaide, and Perth) between June 11, 2010, and March 14, 2013, among 440 healthy term (>36 weeks' gestation) infants aged less than 5 days at recruitment. Statistical analysis was performed from March 1, 2015, to June 2, 2016.InterventionNewborns received HBV and, after stratification by maternal receipt of adult-formulated aP-containing vaccine (tetanus toxoid, reduced diphtheria toxoid, and pertussis antigen content [Tdap]) prior to pregnancy, were block randomized to receive the aP vaccine (without diphtheria or tetanus) within 5 days of birth or not. At 6, 16, and 24 weeks, infants received a hexavalent vaccine with pediatric-formulated diphtheria, tetanus and pertussis antigens (DTaP), Haemophilus influenzae type b (Hib), HBV, and polio vaccine, as well as the 10-valent pneumococcal conjugate vaccine.Main outcomes and measuresDetectable (>5 enzyme-linked immunosorbent assay units per milliliter) and geometric mean concentrations of IgG antibody to pertussis toxin (PT), pertactin, and filamentous hemagglutinin at 6, 10, and 24 weeks stratified by maternal Tdap history, and antibody at 32 weeks to HBV, Hib, polio, diphtheria, tetanus, and pneumococcal serotypes. The primary outcome was detectable IgG to both PT and pertactin at 10 weeks.ResultsA total of 440 infants (207 girls and 233 boys; median gestation, 39.2 weeks) were randomized to receive the aP vaccine plus HBV (n = 221) or HBV only (control group; n = 219). At 10 weeks, 192 of 206 infants who received the aP vaccine (93.2%) had detectable antibodies to both PT and pertactin vs 98 of 193 infants in the control group (50.8%) (P < .001), with the geometric mean concentration for PT IgG 4-fold higher among the group that received the aP vaccine. At age 32 weeks, all infants (n = 181 with sera available for testing) who received the aP vaccine at birth had detectable PT IgG and significantly lower IgG geometric mean concentrations for Hib, hepatitis B, diphtheria, and tetanus antibodies. Local and systemic adverse events were similar between both groups at all time points.Conclusions and relevanceThe monovalent aP vaccine is immunogenic and safe in neonates and, if licensed and available, would be valuable for newborns whose mothers did not receive the Tdap vaccine during pregnancy.Trial registrationhttp://anzctr.org.au Identifier: ACTRN12609000905268.

Dataset Information

Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial.

Publications

Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets