Current Advances of Plant-Based Vaccines for Neurodegenerative Diseases

Abstract

Neurodegenerative diseases (NDDs) are characterized by the progressive degeneration and/or loss of neurons belonging to the central nervous system, and represent one of the major global health issues. Therefore, a number of immunotherapeutic approaches targeting the non-functional or toxic proteins that induce neurodegeneration in NDDs have been designed in the last decades. In this context, due to unprecedented advances in genetic engineering techniques and molecular farming technology, pioneering plant-based immunogenic antigen expression systems have been developed aiming to offer reliable alternatives to deal with important NDDs, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Diverse reports have evidenced that plant-made vaccines trigger significant immune responses in model animals, supported by the production of antibodies against the aberrant proteins expressed in the aforementioned NDDs. Moreover, these immunogenic tools have various advantages that make them a viable alternative for preventing and treating NDDs, such as high scalability, no risk of contamination with human pathogens, cold chain free production, and lower production costs. Hence, this article presents an overview of the current progress on plant-manufactured vaccines for NDDs and discusses its future prospects.

Keywords: Alzheimer’s disease; Parkinson’s disease; immunotherapy; molecular farming; neurodegenerative disorders; novel therapeutic strategies; plant-based vaccines.

Figure 1

Schematic representation of the pathophysiology of NDDs. (A) The microenvironment of a normal brain is characterized by the absence of abnormally expressed proteins and correct nervous function. (B) Neurodegeneration is indicated by aberrant protein accumulation, the activation of CNS-resident immune cells, cytokine-mediated neuroinflammation, a pro-oxidative environment, nerve cell damage, and immune-mediated neuronal death.

Figure 2

Mechanism of action of peptide-based vaccines against NDDs. Following oral or parental vaccination, APCs use PRRs to identify foreign antigens; these are internalized and processed by the proteasome to be expressed on the cell surface as peptide epitopes in the MHC type II. Afterward, CD4+ T cells interact with APCs, prompting the activation of B cells. As a result, plasma cells (active B cells) produce highly specific antibodies against the NDD-related epitope. Antibodies move through the blood circulation and pass the blood-brain barrier to reach the CNS, where they bind to the NDD-associated proteins in order to eliminate them or impede their functions.

Figure 3

Production of plant-made vaccines against NDDs. Firstly, genetic engineering techniques are employed to generate plant expression systems. Upon heterologous antigen expression, animal models are immunized using either the purified antigens, seeds, plant organs, or lyophilized plants, either as biomass or encapsulated. Alternatively, at the clinical level, the goal is to be able to safely immunize humans with plant-derived vaccines, so this can result in an efficient antibody response for prevention and treatment against NDDs.

Figure 4

Future directions for the development of plant-based vaccines targeting NDDs. Extensive animal studies are required to ensure plant-derived vaccines’ safety. Furthermore, thermal stability studies should be performed to avoid the need for cold-chain transportation and storage. Additionally, future research should focus on developing plant-made vaccines against other NDDs and exploring the possibility of combining different epitopes in a single vaccine to deal with multiple NDDs concurrently. One of the main advantages of plants is that they can serve as a delivery vehicle for pharmaceuticals, so this property must be taken advantage of and improved to facilitate antigen recognition in the immune cells of the digestive system. On the other hand, several biotechnological techniques could be harnessed with the aim of efficiently producing recombinant NDD-related antigens and antibodies in plants. Finally, upcoming investigations could leverage the advantages of systems such as rice, microalgae, plant viruses, and medicinal plants.