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Evaluation of safety and immunogenicity of a group a streptococcus vaccine candidate (mj8vax) in a randomized clinical trial.

Affiliation(s)

(Sekuloski, Griffin, O'Rourke, Marquart, McCarthy) Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia
(Batzloff, Hartas, Pandey, Good) Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
(Griffin, Elliott) Q-Pharm Pty Ltd, Brisbane, Australia
(Griffin) Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Australia
(Griffin, McCarthy) University of Queensland, Brisbane, Australia
(Parsonage) Australian Centre for Health Service Innovation, Queensland University of Technology, Brisbane, Australia
(Rubin) Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
(Carapetis) Telethon Kids Institute, University of Western Australia, Perth Children's Hospital, Perth, Australia
(Sekuloski) PharmOut Ltd Pty, Brisbane, Australia
(Rubin) Independent Consultant, Bethesda, MD, United States

Year

2018

Citation

PLoS ONE. Vol.13(7), 2018.

Journal

PLoS ONE

Conference name

Conference location

Grant information

Organisation: (NHMRC) National Health and Medical Research Council Organisation No: 501100000925 Country: Australia
Organisation: (NIH) National Institutes of Health Organisation No: 100000002 Country: United States
Organisation: NSW Department of Industry Organisation No: 501100007906 Country: Australia
No: U01AI060579 Organisation: Project Management Organisation No: 100006163 Country: United States
This work has also been produced as part of the activities of The Lowitja Institute.

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 mug 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.Copyright © 2018 Sekuloski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed ID

29965967 [https://www.ncbi.nlm.nih.gov/pubmed/?term=29965967]

Type

Article

Study type

Randomised controlled trial

Subjects

Infectious diseases

Keywords