Safety and Immunogenicity of Group A Streptococcus Vaccine Candidate MJ8VAX

Intramuscular administration of a novel group A streptococcus (GAS) vaccine candidate (MJ8VAX) was demonstrated to be safe and immunogenic according to a study recently published in PLoS One.

Streptococcus pyogenes, also known as GAS, is a serious human pathogen that can, if left untreated, develop into life-threatening conditions, including acute rheumatic fever (ARF) leading to rheumatic heart disease (RHD) and acute post-streptococcal glomerulonephritis, which can result in permanent renal damage. Approximately 319,400 deaths each year are the result of RHD, and a further 160,000 deaths/year are caused by invasive GAS disease.

Presently, there is no strategy for prevention of GAS infection, highlighting the need for a prophylactic vaccine. A novel conjugate vaccine candidate (MJ8VAX) consists of a synthesized and acetylated peptide antigen (J8) that was conjugated to diphtheria toxoid (DT) as a carrier protein, and formulated with alum (alhydrogel, 2% aluminum hydroxide) adjuvant. 

Pre-clinical studies demonstrated that administration of J8-DT with Alum by intramuscular injection was well tolerated and did not induce the immunopathogenesis of RF/RHD. This control phase 1 clinical trial (trial registration identifier: ACTRN12613000030774) reported that the novel acetylated peptide-protein conjugate vaccine candidate MJ8VAX (J8-DT) was safe and resulted in immunogenicity when given intramuscularly to healthy adults.

A total of 10 healthy adults were included and randomly assigned 4:1 to receive the vaccine candidate (N=8) or placebo (N=2). A single dose of the vaccine candidate (MJ8VAX) contained 50 µg of peptide conjugate (J8-DT) absorbed onto aluminum hydroxide and resuspended in phosphate-buffered saline in a total volume of 0.5 mL. Control participants received normal saline. Vaccine safety was assessed by monitoring local and systemic adverse events (AEs) following administration. Vaccine immunogenicity was assessed by measuring the levels of peptide (anti-J8) and toxoid carrier (anti-DT)- specific antibodies in serum samples on days 0, 28, 180, 266, and 350.

A total of 13 AEs were recorded; 2 were mild in severity (headache and abdominal discomfort) and associated with the investigational vaccine. The remaining AEs were not associated with the investigational vaccine.

On day 0, the concentration of anti-J8 immunoglobin (Ig)G ranged from 1.07 to 1.96 µg/mL and the concentration of anti-DT IgG ranged from 9.29 to 40.33 µg/mL for all participants. On day 28, there was a clear trend of increased anti-J8 IgG antibody levels (1.82- 9.27 µg/mL) and anti-DT IgG concentrations (95.62-537.99 µg/mL) among participants who were administered the MJ8VAX dose. There was no increase in either anti-J8 (1.22-1.56 µg/mL) or anti-DT IgG (43.08-48.21 µg/mL) concentrations in the 2 subjects administered the placebo. On day 180, anti-J8 IgG concentrations in the vaccinated cohort decreased to levels close to baseline and remained at baseline levels on day 266 and day 350. However, anti-DT IgG concentrations remained elevated in most participants in the vaccinated cohort on day 180 (30.56- 386.39 µg/mL); anti-DT IgG concentrations were also elevated in 2 of the 3 participants analyzed on days 266 and 350.

Overall, the investigators concluded that, “this is a first report that shows that the conserved region of the GAS M protein can be used to design a safe vaccine candidate that could be effective against different strains of GAS.”

Reference

Sekuloski S, Batzloff MR, Griffin P, et.al.  Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial. PLoS One. 2018;13(7):e0198658.