Primary amoebic meningoencephalitis (PAM), or naegleriasis, is an infrequent yet severe neurological infection triggered by the protozoan parasite Naegleria fowleri. Harnessing cutting-edge scientific breakthroughs and utilizing a comprehensive approach, our company is dedicated to providing pioneering solutions in the development of vaccines and therapeutics for PAM.
Introduction to Primary Amoebic Meningoencephalitis
Primary amoebic meningoencephalitis (PAM) is a grave and frequently fatal neurological condition caused by the free-living amoeba Naegleria fowleri. This microorganism is commonly present in warm freshwater habitats like lakes, hot springs, and inadequately maintained swimming pools. Infection occurs when tainted water enters the body through the nasal passages, often during aquatic activities. The amoeba travels along the olfactory nerve to the brain, triggering rapid inflammation and destruction of brain tissue, manifesting in symptoms such as intense headaches, fever, nausea, vomiting, and altered mental state. The disease progresses swiftly, with a median time from symptom onset to death of about five days, and a mortality rate exceeding 97%.
Fig.1 Infection mechanism and forms of N. fowleri. (Güémez A., et al., 2021)
Vaccine Development for Primary Amoebic Meningoencephalitis
- mRNA-Based Vaccines
Recent advancements in vaccine technology have led to the exploration of mRNA-based vaccines targeting Naegleria fowleri. These vaccines utilize messenger RNA to instruct host cells to produce specific proteins that mimic the amoeba's antigens, eliciting an immune response.
For instance, a proposed mRNA vaccine identifies multiple B-cell and T-cell epitopes derived from pathogenic proteins of the amoeba. The incorporation of adjuvants, such as RpfE, enhances the immunogenicity of these constructs, leading to robust immune activation. Predictive modeling has indicated that such vaccines could generate long-lasting memory immune responses, crucial for combating the rapid progression of PAM.
- Multi-Epitope Vaccines
In addition to mRNA vaccines, multi-epitope vaccine constructs represent a promising approach. These vaccines combine various epitopes from different proteins of Naegleria fowleri, aiming to provoke a comprehensive immune response. By activating both humoral and cellular immune pathways, these vaccines have the potential to enhance protection against the pathogen. Computational tools are utilized to identify epitopes that are non-allergenic, non-toxic, and capable of inducing strong immune responses, thus increasing the likelihood of successful vaccine development.
Therapeutics Development for Primary Amoebic Meningoencephalitis
Antimicrobial Agents
Currently, therapeutics options for PAM are limited, and the high fatality rate necessitates urgent therapeutic development. One of the most studied drugs is miltefosine, an alkylphosphocholine that has shown efficacy in laboratory settings against Naegleria fowleri. Initially developed for treating leishmaniasis, miltefosine's potential in PAM has been demonstrated through in vitro studies that indicate its ability to inhibit amoebic growth and promote survival in infected models.
Novel Therapeutics Targeting Pathogenic Mechanisms
Ongoing research is focused on identifying specific molecular targets within Naegleria fowleri to develop novel therapeutic agents. For example, studies have highlighted the role of cathepsin B, a cysteine protease involved in the amoeba's pathogenicity. Inhibition of cathepsin B has been associated with improved survival rates in animal models, suggesting its viability as a drug target.
Our Services
Our vaccine development pipeline includes the identification of antigenic epitopes, formulation of vaccine candidates, and evaluation of immunogenicity through preclinical models. We employ state-of-the-art bioinformatics tools and high-throughput screening to accelerate the discovery process.
In the realm of therapeutics, our focus is on identifying novel compounds with potent amoebicidal activity and minimal toxicity. We utilize a multidisciplinary approach that encompasses medicinal chemistry and pharmacology to optimize drug candidates for PAM therapeutics.
- Model: Primary Amoebic (Naegleria) Meningoencephalitis in Mice
- Species: White Swiss (SW) mice
- Construction Method: Intranasal inoculation with Naegleria fowleri
To ensure our vaccine candidates and drug compounds interact effectively with their targets, we perform molecular docking and dynamic simulations. This technology helps predict the binding affinity and stability of our products, guiding further optimization. If you are interested in our services, please feel free to contact us.
References
- Güémez, Andrea, and Elisa García. "Primary amoebic meningoencephalitis by Naegleria fowleri: pathogenesis and treatments." Biomolecules 11.9 (2021): 1320.
- Naveed, Muhammad, et al. "Development and immunological evaluation of an mRNA-based vaccine targeting Naegleria fowleri for the treatment of primary amoebic meningoencephalitis." Scientific Reports 14.1 (2024): 767.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
