United States scientists have revealed that they are on track to produce cheap doses of Covid-19 vaccines in Botswana-which if approved could boost the country’s supply and those of other developing countries.
US based Keck Graduate Institute (KGI) scientists led by Dean of Research and Research Professor Dr Larry Grill will be building on their success in producing low-cost vaccines for developing countries in collaboration with some stakeholders in Botswana primarily focusing on animal diseases that significantly impact smallholder farmers in Africa.
Grill and his team never considered using their Botswana network to produce human vaccines, because getting human vaccines approved in the U.S. typically takes 10 to 15 years. A report published by KGI indicates that however, with the emergency use authorization brought about by the pandemic, Grill is now working to adapt the vaccine for use against COVID-19. This vaccine is distinct from the COVID vaccines currently on the market in that it is derived from plant viruses, KGI said in the report.
Responding to Sunday Standard queries, Grill confirmed that, “We have discussed working with BVI to make COVID-19 vaccines, but, with the unfortunate early death of the BVI general manager, Dr. George Matlho, things have been put on hold.”
He added that, “Also, I have not been able to come to Botswana to collaborate due to the travel restrictions. We hope to collaborate with BVI on low-cost, plant-derived COVID-19 vaccines for humans.” Botswana Vaccine Institute already adheres to the OIE standard which is recognized by the World Trade Organisation (WTO) Agreement on the Application of Sanitary and Phytosanitary Measures.
While he said he was not aware of an envisaged collaboration between KGI or Grill and Botswana vaccine Institute (BVI) on the production of cheap Covid-19 vaccines, BVI’s General Manager Andrew Madeswi referred this publication to Grill for purposes of establishing the veracity of the envisaged collaborations between the two institutions on production of Covid-19 vaccines in Botswana.
But he added that “BVI confirms that it is aware that the University of Botswana (UB) and Pitzer College from America conceived an idea to explore the use of plant based production using Tobacco Mosaic Virus for the production of cheap livestock vaccines for the African continent on the basis that the method does not need high security biocontainment buildings for production.”
Grill also told Sunday Standard in an emailed response that, “It is correct that we have been working with BVI for approximately 10 years to develop a cattle vaccine against lumpy skin disease, using low-cost, plant-derived vaccines. With BVI, we tested the vaccines in cattle (2018) and the vaccines provided immunity against the lumpy skin disease.”
He said in April, 2019, the KGI lab turned our efforts to develop low-cost, plant-derived vaccines against the COVID-19 disease.
“We have been successful at developing several COVID-19 vaccines that provided antibody responses against the SARS-CoV-2 virus. We are further testing this to identify the best vaccine that can provide immunity against the disease,” he also told this publication.
Madeswi also confirmed that UB later “identified Botswana vaccine Institute Limited (BVI) as the only vaccine manufacture in the country as an important stakeholder hence the invitation for BIV to take part in the project.”
He said in April 2021, a memorandum of understanding was signed between UB, Pitzer and BIV for the development of this technology. “The role of BVI was to carry out clinical testing of candidate vaccine strains identified by the project as well as production and commercialisation of approved vaccine strains,” said Madeswi.
He said the project started with lumpy skin vaccine and candidate vaccine strains were identified and tested adding that, “These candidate vaccine strains are currently undergoing optimization in the United States.”
Madeswi further stated that, “BVI dealt in this project with Professor Larry Grill who whilst he was with Pitzer College of which he has now joined Keck Graduate Institute and continuing with the project.”
The KIG report states that plant viruses do not cause diseases in humans, but your immune system will make antibodies if a plant virus comes into contact with these viruses. As such, viruses from plants can train your immune system to respond appropriately to foreign invaders if the plant virus is “costumed” with a surface protein that looks like a pathogen.
“To take advantage of this feature, Grill and his team changed the outside surface of the plant virus to resemble a real pathogen. Using a virus coat protein fusion, they added the genetic information from a SARS-CoV-2 spike protein to the surface of a Tobacco Mosaic Virus (TMV),” the report says.
It says the TMV fused coat proteins are taken up by the APCs (antigen presenting cells) and displayed on Class II MHC molecules. The Class II molecules interact with the CD4+ (“helper”) T cells to trigger an appropriate cellular immune response.
“Your immune system detects the virus and makes antibodies against the SARS-CoV-2 spike protein,” Grill was quoted as saying in the report. “As a matter of fact, the data that we have shows that memory cells would be ready for the SARS-CoV-2 virus for at least a few years.”
Additionally, they can continue to grow the TMV vaccines in plants, allowing them to produce large amounts of what Grill calls “decorated viruses” in the sense that a pathogen surface protein has been added to the plant viruses.
“Injectable pure material costs less than 15 cents a dose, so when you’re talking about developing countries, that’s pretty important,” Grill reportedly said.
To date, Grill and his team of KGI researchers—which includes Kelvin Phiri, Karen Paco, Grace Wakabayashi, Elena Gonzales, Marie Osire, Jose Mendez, Bonnie Blackman, and Jenny Johnston—have done the bulk of their work vaccinating cattle in Botswana.
“They have a lot of cattle there,” Grill said. “In fact, they have more cattle than humans, and cattle are very important to their economy.”
According to the report, cattle in Botswana have been afflicted with Lumpy Skin Disease (LSD), resulting in reduced milk production, sterility in bulls, damage to hides, and death from secondary bacterial infections, which in turn leads to severe nutritional and economic losses.
After fusing several LSD coat protein peptides to the TMV coat protein to create a vaccine, Grill and his team began vaccinating cattle. Botswana Vaccine Institute assisted with the trials as they collected serum samples every two weeks to check the antibody response.
The results were encouraging, showing that the cattle produced specific antibodies until around day 14 of the trials. “At this point, there’s no more virus in their body, so they stop making antibodies,” Grill was also quoted as saying in the report. “At the same time, they save the memory cells that are protective against the LSD. So now when they’re challenged with the actual LSD virus, they respond very quickly because they have all the right antibodies, and these cattle are not affected by the disease.”
In April 2020, Grill and his team shifted their focus to designing and producing low-cost COVID-19 vaccines.
“They are working with Botswana Vaccine Institute and the Botswana government to secure funding to build a facility in Botswana and produce the vaccines. Their goal is not to compete with the big pharma vaccine companies but rather to produce a low-cost vaccine for developing countries. Compared to vaccines produced in the U.S. and Europe, this vaccine is very affordable to develop,” the report says.
The report says production plants are grown in growth rooms, leaves are harvested 8-10 days post introduction, and the TMV vaccines are purified via a simple precipitation step. Additionally, the virus is very stable and unlike some current COVID vaccines on the market such as the one produced by Pfizer, it doesn’t appear to need to be stored at extremely cold temperatures (which can be problematic when transporting the vaccine to developing countries). In addition to cost and ease of production, Grill sees other advantages.
“The Johnson and Johnson and AstraZeneca vaccines use viruses that actually replicate in your body,” Grill said. “If people are immunocompromised, it can be problematic. However, our virus cannot replicate in humans.”
Thus, Grill’s vaccine may be safer for immunocompromised individuals. While they haven’t started human trials, they have begun conducting trials with mice.
“In our first set of animal trials, we found that the mice make good antibodies, but we don’t know whether these antibodies can neutralize the virus,” Grill reportedly said. “So we’re now conducting another set of trials with the J. Craig Venter Institute in San Diego. If it’s successful, then our plan is to go to Botswana and build a facility in hopes that we can actually finish it in time to protect people against COVID-19. But if it does take longer, we know this is not the last pandemic.”
Another benefit of this vaccine is that it can protect against many different strains at once because they are not limited to using one protein.
“We can put many different proteins into the plants because it’s the same cost to make the vaccine,” Grill was quoted as saying.
Grill appreciated his KGI research team—including Phiri, a post-doc from Zimbabwe who has worked with him for many years—for the passion and commitment they bring to the endeavour.
“These students work in my lab because they enjoy it, and they really understand what we’re doing,” Grill said. “I don’t have to explain—for example—how to genetically add the sequences to the plants because they already get it. They really get excited about the work.”
