Primary amoebic meningoencephalitis (PAM), or naegleriasis, induced by Naegleria fowleri is a severe neurological disease that is rarely encountered. 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
PAM, or Primary amoebic meningoencephalitis, is a serious and often deadly condition of the burning by the free living amoeba called Naegleria fowleri. This organism is abundantly present in warm freshwater such as lakes, hot springs, and poorly kept swimming pools. Infection occurs when the contaminated water enters the body through the nose while engaging in water related activities. The amoeba follows the olfactory nerve to the brain and induces a severe inflammatory response along with rapid tissue necrosis. This results in intense headaches, fever, nausea, vomiting and altered state of one’s mental wellbeing. The median time between the first onset of the symptoms and death is about five days. The disease progresses at a very rapid pace and has a mortality exceeds 97%.
Fig.1 Infection mechanism and forms of N. fowleri. (Güémez A., et al., 2021)
Vaccine Development for Primary Amoebic Meningoencephalitis
- mRNA-Based Vaccines
The focus of recent advancements in vaccine development is targeted towards the use of mRNA vaccines against Naegleria fowleri. This type of vaccine capitalizes on the unique biological pathways of the host cells, using the host cell‘s own MRNA to enable the immune system to combat the amoeba infection.
This is evidenced in the mRNA vaccine that is aimed for several T-cell and B-cell epitopes derived from pathogenic proteins of the amoeba. Adding RpfE adjuvants to these constructs further enhances the immunogenicity of these constructs and results in the mounting of robust immune responses. In silico modeling suggests that these types of vaccines can elicit strong and durable immune memory which becomes very pertinent considering the rapid escalation of PAM.
- Multi-Epitope Vaccines
Constructing a multi-epitope vaccine is a very promising method for developing vaccines apart from mRNA vaccines. These are designed to include multiple epitopes from different proteins of Naegleria fowleri in order to elicit broad immunity. Vaccination with these vaccines might increase protection to the microorganism by inducing both humoral and cellular arms of defense. Immunoinformatic tools are applied in the selection of epitopes which are expected to be non-allergenic, non-toxic and immunogenic to increase the chances of success.
Therapeutics Development for Primary Amoebic Meningoencephalitis
Antimicrobial Agents
Currently, there are limited therapeutic solutions for PAM, and the alarming rate of mortality underscores the necessity of more research in the area. One of the most widely used drugs is miltefosine, an alkylphosphocholine which is effective against naegleria fowleri. Miltefosine, developed originally for the treatment of leishmaniasis, has also shown in vitro effectiveness in PAM by inhibiting amoebic growth and in subsequent models improving recipient survival.
Novel Therapeutics Targeting Pathogenic Mechanisms
The primary focus of ongoing work is to identify specific molecular targets available in Naegleria fowleri for the development of new drug targets. Specifically, some research works have drawn attention to the action of cathepsin B, a cysteine protease which is involved in the cytopathic activity of the amoeba. Cathepsin B inhibition is reported to enhance survival rate in laboratory animals, and therefore, it offers a good starting point for developing new drugs.
Our Services
From designing the antigenic epitopes to the analysis on immunogenicity towards preclinical models, these are but few activities within our vaccine development pipeline. The use of modern bioinformatics tools alongside high-throughput screening speeds up the discovery phase as much as possible.
One of the areas that captures our interest in therapeutics relates to the new compounds that exhibit profound amoebicidal activities with low toxicity. We implement an integrated approach that combines medicinal chemistry and pharmacology for the rational design of 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.
