MucoShield – Development of a Mucosal ORFV Vector Vaccine to Prevent Respiratory Infections Caused by the Human Metapneumovirus (HMPV)

Challenge

Human Metapneumovirus (HMPV) is one of the leading causes of acute respiratory infections, resulting in hundreds of thousands of hospitalizations annually, particularly among vulnerable populations. Despite this high disease burden, no approved vaccine exists to date, which can be attributed to several scientific and technical challenges. Classical systemic vaccines fail to induce adequate local immunity at the respiratory mucosa, where the virus enters the body. Furthermore, the virus exhibits two lineages (A and B) with antigenic diversity, meaning an effective vaccine must cover both lineages. Additionally, a great hurdle lies in translating promising vaccine candidates into GMP-compliant production, which requires robust, scalable processes and stable formulations that meet the specific requirements of intranasal application.

Objectives and project plan

The MucoShield consortium aims to advance an ORFV-based HMPV vaccine candidate to a clinically compatible lead candidate. The focus lies on developing an intranasal formulation that enables needle-free immunization and specifically induces mucosal antibodies and tissue-resident T cells at the nasal mucosa.

Prime Vector Technologies drives the scientific strategy by designing and constructing multivalent HMPV antigen constructs, characterizing the vectors in vitro, planning and conducting the preclinical immunogenicity and challenge studies, and simultaneously adapting the existing GMP manufacturing process for the HMPV lead candidate, while the NMI establishes the necessary immunoassays to evaluate antibody and T-cell responses, compares different vaccine candidates in preclinical models, and identifies immunological marker combinations as predictive parameters for later clinical development.

The Virus-Based Therapies and Technologies Department at Fraunhofer IGB makes decisive contributions to the project's success with two key work packages. In the formulation development work package, the institute is responsible for developing a stable, mucoadhesive intranasal formulation compatible with the viral particle structure and nasal mucosa. This includes systematically screening suitable excipients, optimizing buffer systems for stability and bioactivity, and comprehensive physicochemical characterization regarding viscosity, osmolarity, particle size, and aggregation behavior under various storage and stress conditions.

In the upstream and downstream optimization work package, Fraunhofer IGB establishes a scalable diafiltration process for buffer exchange and optional concentration that can be directly integrated into the existing ORFV manufacturing process. The goal is to develop a technologically robust and regulatorily compatible formulation module for later GMP production.

Impact

The MucoShield project addresses a significant medical need and creates sustainable value on multiple levels. From a medical perspective, an intranasal vaccine could block infections directly at the entry point and reduce virus transmission, which is particularly relevant for vulnerable groups such as children and the elderly.

From a technological innovation perspective, the intranasal formulation and scalable diafiltration process developed at Fraunhofer IGB represent innovative CMC modules that can be applied to other respiratory vaccines and strengthen the ORFV platform for future applications.