An international consortium has been formed, pooling resources to develop a nasally delivered, cross-strain protective CoV-2 mRNA vaccine. The consortium aims to initiate clinical testing in early 2021.
Companies and organisations involves include:
- eTheRNA Immunotherapies, which is is applying its TriMix platform comprising three mRNAs encoding proteins (caTLR4, CD40L and CD70) that activate dendritic cells which then act to promote a strong CD4 and CD8 T cell response.
- EpiVax, whose in silico epitope prediction and design technology will identify the target in SARS-CoV-2.
- REPROCELL, whose nasal atomizer and a proprietary formulation delivers the mRNA to the nasal mucosa, optimising expression.
- Nexelis, an immunology-focused CRO bringing assay development, lab testing and validation expertise.
- Centre for the Evaluation of Vaccination (CEV) of the University of Antwerp, a clinical trials centre with the capability to conduct trials from Phase I-IV.
eTheRNA press release follows:
PRESS RELEASE
eTheRNA Immunotherapies , a clinical-stage company developing vaccines and immunotherapies from its proprietary mRNA TriMix platform, today announced that a consortium has been formed with North American and European partners to develop a novel mRNA vaccine against CoV-2 and preclinical development has started. Chinese partners may be added in the consortium in due course.
Administered intranasally, the proposed vaccine is intended primarily for high risk populations such as healthcare workers and families of confirmed cases. It is also designed to be protective against future variations of the virus by targeting conserved epitopes from the whole CoV-2 genome. eTheRNA and its partners EpiVax, Nexelis, REPROCELL and CEV* have extensive experience in the mRNA vaccine field and this will help accelerate progress towards clinical trials with patient enrolment expected in early 2021.
Explaining the aims of the consortium, Steven Powell, eTheRNA’s Chief Executive Officer, said: “Viral variation means traditional medicinal and preventive vaccine approaches may fall short when confronted with seasonal or outbreak situations. A vaccine to defend against current and future outbreaks of coronavirus and other respiratory viral pathogens should be robust against viral genome changes, provide a platform that enables rapid introduction of a new viral target, be easy and safe to administer and be scaleable and suitable for stockpiling. The innovative vaccine program we have started with our partners incorporates all of these essential features.”
Traditional vaccines are based on generating an antibody response to outer surface viral protein targets. However, viral variation may greatly reduce the effectiveness of this approach. For example, the SARS-CoV-2 outer surface spike protein (S) is less than 40% homologous to SARS-CoV-1. Furthermore, it has also been reported in several cases that vaccines with suboptimal antibody response (too low or not neutralising) have facilitated viral entry and been linked to disease enhancement.
The eTheRNA consortium’s approach selects conserved epitopes from the whole viral genome. Creating a vaccine that mounts a strong cellular (T cell) based response against these epitopes offers a better chance to overcome viral variability. Intranasal delivery has been chosen since the mucosa of the upper respiratory tract are the immune system’s primary line of defence. A strong nasal T cell effector and memory response is claimed to fight viral replication, colonisation of the lung and thus disease. mRNA has also been demonstrated to induce strong T cell responses by intranasal delivery.
The development programme has been initiated and is focused on a vaccine candidate that integrates 3 different technologies:
- eTheRNA’s proprietary Trimix technology: an mRNA-based vaccine adjuvant that stimulates dendritic cells into activating a strong CD4 and CD8 T cell response.
- A combination of T cell epitopes from the virus brought together on a single mRNA construct. For SARS-CoV-2 this will employ an in silico epitope prediction and design approach from EpiVax. to identify the target.
- An intranasal vaccine delivery platform using a nasal atomizer and a proprietary formulation that delivers the mRNA to the nasal mucosa and optimises expression. One of the most promising formulation candidates is being repurposed for clinical use in collaboration with REPROCELL.
Powell concluded: “While valuable initiatives and strong support are being deployed into the development of medicinal and vaccine solutions for immediate use against SARS-CoV-2, it is also important that development of solutions for the longer term should also start as soon as possible. Our target is to bring this into clinical testing in early 2021.”
Link to Press Release.