Development of Versatile and Cost-Effective Next-Generation Vaccines through Multivalent Approaches
Led by Dr Julen Tomás Cortázar (University College Dublin, Ireland), with Assoc Professor Apichai Tuanyok (University of Florida, USA) and Dr Kata Horvati (HUN-REN Research Centre for Natural Sciences, Hungary), and Prof Siobhán McClean (University College Dublin, Ireland)
Project Aim
Melioidosis infection is caused by the intracellular Burkholderia pseudomallei (Bp), a Gram-negative bacterium with 89,000 deaths per year worldwide, mostly in tropical and subtropical areas including LMIC countries like Thailand. Moreover, diabetes mellitus, which has a concerning increasing prevalence in these countries, is the major risk for severe melioidosis. However, the bacteria is highly resistant to antibiotics and there is no vaccine available yet. Modern vaccinology demands the use of more cost-effective and potent next-generation vaccine platforms against bacterial infections like melioidosis for LMIC countries. As an intracellular pathogen, the disease is contended by dominant Interferon-γ (IFN-γ) responses. The fact that potent adenoviral-vectored vaccines against the intracellular Mycobacterium tuberculosis (mtb) are highly developed makes this vaccine platform appropriate for Bp as well. Additionally, IFN-γ responses have already been observed in mRNA vaccines against bacterial infections and WHO and Medicines Patent Pool (MPP) are promoting mRNA technology in LMIC countries. Therefore, mRNA vaccine platform, emerged as cost-effective, rapid, safe and potent immunogenic since COVID-19 pandemic, is also a good candidate platform for melioidosis. Alternatively, peptide-based nanovaccinology has also arisen as a promising vaccine platform due to their enhanced immunogenicity, cost-effective production and non-refrigerated transportation. In summary, to ensure accessibility in LMICs, it is vital to evaluate next-generation melioidosis vaccine platforms that combine cost-effectiveness, robust immune responses, and safety. BpOmpW, our highly promising melioidosis vaccine candidate, elicits strong IFN-γ responses across T-cell and NK subsets and has shown durable protection (up to 81 days).Moreover, its immunogenic peptide P7 also elicited IFN-γ in different T-cell subsets and was significantly recognized by sera from melioidosis survivors with diabetes. Additionally, BpPhbB antigen, along with its peptide P1, has demonstrated robust IFN-γ responses in T-cell and NK subsets in re-stimulation assays but has not yet been tested in challenge models. Altogether, To enhance the breadth and effectiveness of melioidosis vaccines, the proposal aims to transition from conventional subunit vaccines to next-generation platforms (adenoviral-vectored, mRNA, and peptide-based nanovaccines) incorporating our most promising antigens, their immunogenic peptides and multivalent approaches against melioidosis.
