An assessment of a GMP schistosomiasis vaccine (SchistoShield®)

Abstract

Introduction: Schistosomiasis is a neglected tropical disease that puts over 200 million people at risk, and prevention options are sparse with no approved vaccine. Our vaccine candidate, SchistoShield^®, is based on an approximately 87 kDa large subunit of calcium activated neutral protease - termed Sm-p80 - combined with a potent TLR4 agonist-based adjuvant. SchistoShield^® has been shown to prevent disease throughout the parasitic life cycle - including egg, juvenile, and adult worm stages - in numerous animal models up to and including baboons. SchistoShield^® has been shown safe in both preclinical toxicology studies in rabbits and in a Phase 1 clinical trial in the USA. A Phase 1b trial was initiated in 2023 in endemic regions of Africa, and to date no serious safety signals have been reported.

Methods: In preparation for large-scale Phase 2 clinical trials and eventual vaccine deployment, the Sm-p80 antigen production process has been transferred to a manufacturing organization, Quratis Corporation in South Korea, which specializes in preparation of vaccines for large-scale European and African trials. The process of scaling from our current production level of ~2000 vaccine doses, to a process that will generate more than 100 million doses has required multiple improvement steps in the process including fermentation, downstream purification of the protein antigen, lyophilization, and fill and finish.

Results: In this study, we detail the large-scale production process of the SchistoShield^® protein product by Quratis. In addition, an effort was made to analyze and compare the Quratis-made lot of Sm-p80, referred to as QTP-105, to the cGMP lot of Sm-p80 which is in use in human trials in the USA and Africa, referred to as Sm-p80 DP (made in USA). We show that QTP-105 demonstrates excellent potency, purity, identity, and endotoxin levels compared to our Phase 1 Sm-p80 DP and is suitable for use in Phase 2 studies and beyond.

Keywords: SchistoShield ®; Sm-p80; quality assessment; schistosomiasis vaccine; technology transfer; vaccine development; vaccine trials.

FIGURE 1

Physical appearance of Sm-p80 DP and QTP-105 drug product (DP) before (A) and after (B) reconstitution in sterile water for injection (WFI). Post-reconstitution photos were taken within 5 minutes after complete reconstitution.

FIGURE 2

SDS-PAGE gel (A) and western blots (B, C) confirming identity and purity of Sm-p80 protein in Sm-p80 DP and QTP-105. Gels were transferred onto membranes before incubation with primary and secondary antibody dilutions according to methods. Sm-p80 protein was identified by use of immunized baboon sera and a monoclonal mouse antibody (SMab14) (B), and absence of E. coli host cell proteins was verified for purity (C). Sm-p80 bands are indicated with red arrows. Pictures were taken within 5 minutes of termination of TMB-HRP reaction.

FIGURE 3

Mass spectrometric (MS) peptide mapping analyses of Sm-p80 DP (A) and QTP-105 (B). Products were digested with trypsin before running on stated columns. Resulting peptide products were run against theoretical Sm-p80 digest products, and against the theoretical E. coli host cell protein digest products using ThermoFisher BiopharmaFinder software. Data shown includes the MS chromatogram and the peptide mapping results, with total hits against Sm-p80 protein and E. coli HCP.

FIGURE 4

Potency of Sm-p80 DP and QTP-105 products in mice. Mice (n=10 per group) were immunized using 3 different vials of Sm-p80 DP and 1 of QTP-105. Day 14 after immunization, serum samples were taken for analysis of anti-Sm-p80 IgG by ELISA. Cutoff for negatives is shown as a red dotted line.