Aug 25, 2021, 21:53 pm
Published: August 13, 2021
Given the novelty of SARS-CoV-2, the need for a vaccine—and quickly—was immense. Pfizer and Moderna were able to deliver on the timeline, creating vaccines approved for emergency use a little over a year from the start of the pandemic.
But what if there was a technology that could create effective vaccines in just weeks, rather than months?
The authors of a new Perspectives article published in Science believe such a system could be on the horizon as advances in technology and manufacturing, and recent positive clinical trials, could boost the uptake of molecular farming—or plant-made vaccines and therapeutics.
The use of plants for the production of therapeutic proteins was proposed as an alternative biomanufacturing method in 1986. The first and only plant-derived therapeutic protein for human use was approved in 2012 for the treatment of Gaucher disease.
More recently, a plant-produced influenza virus vaccine completed phase 3 clinical trials with encouraging results, and a phase 3 trial for an adjuvanted plant-made vaccine (CoVLP) against SARS-CoV-2, began in March 2021.
According to the authors—Hugues Fausther-Bovendo and Gary Kobinger of the Laval University (Canada)—for vaccine purposes, plant-produced proteins have several advantages over their more traditional counterparts.
For one, plants express different glycans, which renders plant-derived proteins more immunogenic than those produced from chicken eggs and mammalian or insect cell cultures. Unlike bacteria, plants are capable of post-translational modifications.
Production of plant-based vaccines is simple, and it can be easily scaled up or down based on the number of plants grown. Additionally, unlike traditional production systems, zoonotic pathogens are unable to infect plants and therefore cannot be a source of contaminant in molecular farming-derived products.
Lastly, plant-produced vaccines can be developed to work against new pathogens or emerging disease strains extremely quickly, with the first batch of vaccine candidates produced within 3 weeks.
“The speed of molecular farming is particularly suited for personalized medicine in which pharmaceuticals need to be tailored to individual patients, such as for cancer treatment,” write Fausther-Bovendo and Kobinger.
Such speed would also be suited for novel pathogens, such as SARS-CoV-2 back in January 2019.
While the treatment for Gaucher disease is still considered plant-based, the enzyme is actually produced in a carrot cell culture rather than plants. Thus, the plant-made vaccines against influenza virus and SARS-CoV-2 are expected to be the first therapeutic proteins produced in whole plants for human use.
In previous clinical trials, plant-based vaccines have shown no severe side effects. Initially, there was concern the increased immune stimulation of plant-based therapeutics would lead to hypersensitivity toward select plant components. However, several trials, including the phase 3 influenza one, have shown that is not the case.
In the flu trial involving more than 20,000 adults, a mixture of four separate virus-like particles produced in tobacco plants was not associated with more adverse events or an increase in hypersensitivity reactions compared with individuals who received an approved flu vaccine. Additionally, the plant-based vaccine on trial showed efficacy similar to existing flu vaccines.
Monoclonal antibodies (mAb) are another area where plant-made proteins have shown promise. mAbs for Ebola and HIV have already reached clinical stages of development, and thus far have been shown to be generally well tolerated.
Of course, not every system is perfect and there are some drawbacks to plant-based therapeutics. First and foremost, expensive GMP-compliant facilities are required for the extraction, purification and fill processes of molecular farming.
Additionally, plant therapeutics create a smaller yield than traditional vaccines and antibodies, meaning more materials and production would be needed to create the same amount of drugs. At the same time, doses of plant-based therapeutics are much higher than those required to produce effective vaccines. If the method was to gain in popularity, a large investment in manufacturing infrastructure would be critical. Even so, before large-scale manufacturing could be considered, researchers need to find a way to decrease production costs.
“Until then, the speed of molecular farming will be useful for preclinical and early clinical evaluation of therapeutic candidates,” conclude the authors.
https://www.laboratoryequipment.com/5783...-Vaccines/
Given the novelty of SARS-CoV-2, the need for a vaccine—and quickly—was immense. Pfizer and Moderna were able to deliver on the timeline, creating vaccines approved for emergency use a little over a year from the start of the pandemic.
But what if there was a technology that could create effective vaccines in just weeks, rather than months?
The authors of a new Perspectives article published in Science believe such a system could be on the horizon as advances in technology and manufacturing, and recent positive clinical trials, could boost the uptake of molecular farming—or plant-made vaccines and therapeutics.
The use of plants for the production of therapeutic proteins was proposed as an alternative biomanufacturing method in 1986. The first and only plant-derived therapeutic protein for human use was approved in 2012 for the treatment of Gaucher disease.
More recently, a plant-produced influenza virus vaccine completed phase 3 clinical trials with encouraging results, and a phase 3 trial for an adjuvanted plant-made vaccine (CoVLP) against SARS-CoV-2, began in March 2021.
According to the authors—Hugues Fausther-Bovendo and Gary Kobinger of the Laval University (Canada)—for vaccine purposes, plant-produced proteins have several advantages over their more traditional counterparts.
For one, plants express different glycans, which renders plant-derived proteins more immunogenic than those produced from chicken eggs and mammalian or insect cell cultures. Unlike bacteria, plants are capable of post-translational modifications.
Production of plant-based vaccines is simple, and it can be easily scaled up or down based on the number of plants grown. Additionally, unlike traditional production systems, zoonotic pathogens are unable to infect plants and therefore cannot be a source of contaminant in molecular farming-derived products.
Lastly, plant-produced vaccines can be developed to work against new pathogens or emerging disease strains extremely quickly, with the first batch of vaccine candidates produced within 3 weeks.
“The speed of molecular farming is particularly suited for personalized medicine in which pharmaceuticals need to be tailored to individual patients, such as for cancer treatment,” write Fausther-Bovendo and Kobinger.
Such speed would also be suited for novel pathogens, such as SARS-CoV-2 back in January 2019.
While the treatment for Gaucher disease is still considered plant-based, the enzyme is actually produced in a carrot cell culture rather than plants. Thus, the plant-made vaccines against influenza virus and SARS-CoV-2 are expected to be the first therapeutic proteins produced in whole plants for human use.
In previous clinical trials, plant-based vaccines have shown no severe side effects. Initially, there was concern the increased immune stimulation of plant-based therapeutics would lead to hypersensitivity toward select plant components. However, several trials, including the phase 3 influenza one, have shown that is not the case.
In the flu trial involving more than 20,000 adults, a mixture of four separate virus-like particles produced in tobacco plants was not associated with more adverse events or an increase in hypersensitivity reactions compared with individuals who received an approved flu vaccine. Additionally, the plant-based vaccine on trial showed efficacy similar to existing flu vaccines.
Monoclonal antibodies (mAb) are another area where plant-made proteins have shown promise. mAbs for Ebola and HIV have already reached clinical stages of development, and thus far have been shown to be generally well tolerated.
Of course, not every system is perfect and there are some drawbacks to plant-based therapeutics. First and foremost, expensive GMP-compliant facilities are required for the extraction, purification and fill processes of molecular farming.
Additionally, plant therapeutics create a smaller yield than traditional vaccines and antibodies, meaning more materials and production would be needed to create the same amount of drugs. At the same time, doses of plant-based therapeutics are much higher than those required to produce effective vaccines. If the method was to gain in popularity, a large investment in manufacturing infrastructure would be critical. Even so, before large-scale manufacturing could be considered, researchers need to find a way to decrease production costs.
“Until then, the speed of molecular farming will be useful for preclinical and early clinical evaluation of therapeutic candidates,” conclude the authors.
https://www.laboratoryequipment.com/5783...-Vaccines/