PMID- 29965967 OWN - NLM STAT- MEDLINE DCOM- 20181226 LR - 20230928 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 7 DP - 2018 TI - Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial. PG - e0198658 LID - 10.1371/journal.pone.0198658 [doi] LID - e0198658 AB - 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. TRIAL REGISTRATION: ACTRN12613000030774. FAU - Sekuloski, Silvana AU - Sekuloski S AD - Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia. FAU - Batzloff, Michael R AU - Batzloff MR AUID- ORCID: 0000-0003-0482-0033 AD - The Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia. FAU - Griffin, Paul AU - Griffin P AD - Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia. AD - Q-Pharm Pty Ltd, Brisbane, Australia. AD - Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Australia. AD - The University of Queensland, Brisbane, Australia. FAU - Parsonage, William AU - Parsonage W AD - Australian Centre for Health Service Innovation, Queensland University of Technology, Brisbane, Australia. FAU - Elliott, Suzanne AU - Elliott S AD - Q-Pharm Pty Ltd, Brisbane, Australia. FAU - Hartas, Jon AU - Hartas J AD - The Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia. FAU - O'Rourke, Peter AU - O'Rourke P AD - Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia. FAU - Marquart, Louise AU - Marquart L AD - Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia. FAU - Pandey, Manisha AU - Pandey M AD - The Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia. FAU - Rubin, Fran A AU - Rubin FA AD - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. FAU - Carapetis, Jonathan AU - Carapetis J AD - Telethon Kids Institute, University of Western Australia and Perth Children's Hospital, Perth, Australia. FAU - McCarthy, James AU - McCarthy J AD - Clinical Tropical Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia. AD - The University of Queensland, Brisbane, Australia. FAU - Good, Michael F AU - Good MF AD - The Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia. LA - eng GR - U01 AI060579/AI/NIAID NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180702 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Streptococcal Vaccines) RN - 0 (Vaccines, Conjugate) SB - IM MH - Adolescent MH - Adult MH - Drug-Related Side Effects and Adverse Reactions/classification/pathology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Streptococcal Infections/*drug therapy/immunology/microbiology MH - Streptococcal Vaccines/*administration & dosage/adverse effects MH - Streptococcus pyogenes/drug effects/pathogenicity MH - Vaccination/*adverse effects MH - Vaccines, Conjugate/*administration & dosage/adverse effects/immunology PMC - PMC6028081 COIS- The authors have declared that no competing interests exist. The company Q-Pharm Pty Ltd provides clinical trials services. Q-Pharm Pty, Ltd did not fund this study. In this study they conducted the trial as a fee for service. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2018/07/03 06:00 MHDA- 2018/12/27 06:00 PMCR- 2018/07/02 CRDT- 2018/07/03 06:00 PHST- 2017/09/12 00:00 [received] PHST- 2018/05/06 00:00 [accepted] PHST- 2018/07/03 06:00 [entrez] PHST- 2018/07/03 06:00 [pubmed] PHST- 2018/12/27 06:00 [medline] PHST- 2018/07/02 00:00 [pmc-release] AID - PONE-D-17-33193 [pii] AID - 10.1371/journal.pone.0198658 [doi] PST - epublish SO - PLoS One. 2018 Jul 2;13(7):e0198658. doi: 10.1371/journal.pone.0198658. eCollection 2018.