M-protein based vaccine induces immunogenicity and protection from Streptococcus pyogenes when delivered on a high-density microarray patch (HD-MAP)

Jamie-Lee S Mills,Manisha Pandey,Paul V Fahey,Ainslie Calcutt,Christine Wun,Alexandra C I Depelsenaire,Cesar M Jayashi Flores,Angus H Forster,Simone Reynolds,Jessica Dooley,S Ben Baker,Senthil Murugappan,Michael F Good

doi:10.1038/s41541-020-00222-2

Jamie-Lee S Mills, Manisha Pandey + Show 11 more

Open Access

https://doi.org/10.1038/s41541-020-00222-2

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Abstract

We evaluated vaccination against Streptococcus pyogenes with the candidate vaccine, J8-DT, delivered by a high-density microarray patch (HD-MAP). We showed that vaccination with J8-DT eluted from a coated HD-MAP (J8-DT/HD-MAP), induced similar total IgG responses to that generated by vaccination with J8-DT adjuvanted with Alum (J8-DT/Alum). We evaluated the effect of dose reduction and the number of vaccinations on the antibody response profile of vaccinated mice. A reduction in the number of vaccinations (from three to two) with J8-DT/HD-MAP induced comparable antibody responses to three vaccinations with intramuscular J8-DT/Alum. Vaccine-induced protection against an S. pyogenes skin challenge was assessed. J8-DT/HD-MAP vaccination led to a significant reduction in the number of S. pyogenes colony forming units in skin (92.9%) and blood (100%) compared to intramuscular vaccination with unadjuvanted J8-DT. The protection profile was comparable to that of intramuscular J8-DT/Alum. J8-DT/HD-MAP induced a shift in the antibody isotype profile, with a bias towards Th1-related isotypes, compared to J8-DT/Alum (Th2 bias). Based on the results of this study, the use of J8-DT/HD-MAP should be considered in future clinical development and control programs against S. pyogenes. Furthermore, the innate characteristics of the technology, such as vaccine stability and increased coverage, ease of use, reduction of sharp waste and the potential reduction of dose may be advantageous compared to current vaccination methods.

Highlights

Streptococcus pyogenes (S. pyogenes/ group A Streptococcus/ GAS), is a Gram-positive, beta-haemolytic bacterial pathogen[1] that causes a broad spectrum of human diseases
Coated high-density microarray patch (HD-MAP) were evaluated to determine the extent of vaccine loading with J8-diphtheria toxoid (DT) and the stability of the conjugate on the HD-MAPs
MicroBCA analysis of eluted HD-MAPs showed that the coating process deposited a median loading per MAP for all vaccinations of 26.9 μg J8-DT (7% higher than the 25 μg theoretical load)

Summary

Introduction

Streptococcus pyogenes (S. pyogenes/ group A Streptococcus/ GAS), is a Gram-positive, beta-haemolytic bacterial pathogen[1] that causes a broad spectrum of human diseases. Infection causes significant global disease with over 18 million cases of severe disease[1] and 500,000 deaths annually[2]. The most common infection sites are the skin and upper respiratory tract, resulting in impetigo and pharyngitis respectively[1]. Some of the highest rates of infection occur in Indigenous Australians[3,4] (at least five times higher than non-Indigenous Australians)[3], mostly associated with poverty, overcrowding and difficulties in accessing healthcare services[5]. Primary GAS infections can trigger post-infectious immune disorders[6] such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), due to molecular mimicry of the S. pyogenes M-protein and human cardiac myosin[1,2,7].

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