Plant Expression Systems for Vaccine Production

Plants offer an attractive platform for the production of recombinant vaccines due to their inherent safety, scalability, and relatively low cost of cultivation. Various plant expression systems have been developed and evaluated for producing experimental vaccines. Transient systems utilizing Nicotiana benthamiana and Nicotiana tabacum plants infiltrated with Agrobacterium or viral vectors carrying vaccine genes have shown promise in producing high levels of vaccine antigens within 2-3 weeks. However, transient expression systems require large-scale cultivation and processing of fresh plant material at each production run. On the other hand, stably transformed plants by Agrobacterium-mediated transformation or direct DNA delivery can produce vaccine proteins over multiple generations, paving way for continuous and reproducible antigen production. Both transient and stable plant systems have demonstrated efficacy against diverse pathogens in animal studies with multiple vaccine candidates advancing to human clinical trials.

Thermostability of Plant-based Vaccines

An important advantage of plant-based systems is their ability to produce thermostable recombinant vaccines. Plant cells have specialized compartments called plastids and vacuoles that provide an oxidative protein folding environment similar to mammalian endoplasmic reticulum and Golgi. Vaccines produced in plants can adopt bioactive conformation and form multimeric structures observed with conventional vaccines. Also, plant biomass and plant cell walls protect recombinant antigens from degradation, allowing storage and transport of plant-derived vaccines without cold chain requirements. The thermostability of plant-produced vaccines could overcome major logistic challenges associated with vaccine delivery in resource-poor settings where refrigeration is unavailable. Numerous studies have shown plant-made Vaccines to retain immunogenicity after storage at 25-37°C for several months and even after brief exposure to 100°C.

Plant-based Vaccines Against Major Diseases

Plant-based vaccines expression platforms have been leveraged to produce vaccine candidates against many infectious diseases with global impact. Prototypes developed include vaccines against diarrhea-causing rotaviruses, pneumococcal pneumonia, Japanese encephalitis virus, hepatitis B virus, ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Influenza virus etc. Major accomplishments include successful completion of Phase I and II clinical studies of plant-produced vaccine against hepatitis B, diarrheal disease caused by ETEC bacteria, and pandemic influenza H1N1 virus establishing the safety and immunogenicity of plant-derived vaccines in humans.

Plant-based Norovirus Vaccine

Norovirus infection is a major cause of acute gastroenteritis worldwide with sporadic epidemics affecting people of all ages. A well-tolerated and affordable norovirus vaccine is needed for prevention, especially in high-risk groups like healthcare workers and military personnel. Researchers at Kentucky Bioprocessing, Inc. developed a Norwalk virus-like particle (VLP) based vaccine candidate against the most common genogroup I norovirus in plants. The VLPs self-assembled in plant chloroplasts mimicking the native structures found in mammalian systems. Pre-clinical animal testing showed the plant-made VLP vaccine to be highly immunogenic, inducing strong systemic and mucosal antibodies after oral administration. No cold-chain was required during storage and transport since the plant material maintained structural integrity even after exposure to 55°C for 10 days. Preliminary human trials are underway to assess vaccine safety and immunogenicity, highlighting the promise of plant-production platforms for affordable norovirus control.

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