mRNA-LNP Multiantigenic vaccine against Ornithodoros soft-ticks vectors of African Swine Fever virus (MARNAVAC)
Código del proyecto: PID2022-136644OB-I00.
Funding: Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) y Fondo Europeo de Desarrollo Regional (FEDER).
Duration: 01/09/2023 – 31/08/2027
Total budget: 225.000€
Participating entities: IRNASA (CSIC).
Summary: Ornithodoros erraticus and Ornithodoros moubata are the primary vectors of African Swine Fever (ASF) and Human Relapsing Fever (TBRF) in the Mediterranean and Africa. The prevention and control of both diseases require the elimination of Ornithodoros from the human environment, and anti-tick vaccines have emerged as a control method with clear advantages over the use of acaricides. Tick midgut and salivary gland proteins are part of the tick-host interface and perform vital functions for tick survival, which is why they have been successfully used as antigenic targets for tick-vaccine development. Although completely effective vaccines have not been achieved with any of these antigens separately, their combined use in multi-antigen vaccines increases their protective efficacy by simultaneously targeting several biological processes. Therefore, in order to improve multi-antigen vaccines, it is necessary to experimentally validate new protective antigens, preferably using innovative vaccine platforms that overcome the limitations of traditional ones based on recombinant proteins. The novel vaccine platform based on mRNA encapsulated in lipid nanoparticles (mRNA-LNP) is effective, safe, versatile, rapidly adaptable, and allows the combination of several mRNAs in multi-antigen formulations. Additionally, it facilitates the in vivo generation of antigens that are difficult to express with other systems, preserving conformational and glycan epitopes that are lost in recombinant antigens, thus generating more potent and effective immune responses. In this project, our general objectives are (A) to adapt mRNA-LNP technology to Ornithodoros antigens in order to (B) develop innovative, more effective, and affordable multi-antigen vaccines. Our proposal will be developed through the following specific objectives: (1) optimization of the mRNA-LNP platform for the production of Ornithodoros antigens; (2) demonstration of its greater efficacy compared to recombinant vaccines; (3) validation of new protective antigens of Ornithodoros using the mRNA-LNP platform, and (4) design, production, and evaluation of new mRNA-LNP multiantigenic vaccines based on combinations of salivary and midgut antigens. The results of the proposal will generate new scientific-technical knowledge useful for other researchers in the field of antiparasitic vaccines, including other acari, insects, and helminths. They will also facilitate the control of Ornithodoros tick vectors and the diseases they transmit, helping to reduce the economic damage of ASF and the health risks of TBRF.
