By B Medical…
Why Promising Malaria Vaccines Need a Modern Cold Chain
Each year malaria kills hundreds of thousands of people – mostly children – around the globe, and according to a report by the WHO, in 2021 nearly half of the world’s population was at risk of malaria. This included infants, children under 5 years of age, pregnant women, patients with HIV/AIDS, etc. Moreover, over the two peak years of the pandemic, COVID-related disruptions have caused 13 million more malaria cases and 63 000 more deaths. About 247 million people were infected by malaria in 2021 with about 619 000 fatalities (source: World Malaria Report 2021, WHO).
Around 95% of the global malaria cases and about 96% of fatalities happen in the African region, with four countries accounted for almost half of all malaria deaths worldwide: Nigeria (31.3%), the Democratic Republic of the Congo (12.6%), Tanzania (4.1%) and Niger (3.9%).
A disease that is hard to prevent and cure
Malaria is a curable disease, but it is difficult to prevent and treat due to the high adaptability of the vector and parasites involved. The malarial parasite Plasmodium counts several species causing the disease and each of them has a very complex life cycle. The deadliest one is Plasmodium falciparum whereas Plasmodium vivax is the most widespread. In addition to that, the mosquito vector Anopheles has around 30 to 40 species under its name that can transmit the disease, each of which has different behavioural and ecological characteristics. Scientists around the world have been working on the genomics of the parasites as well as the vectors to find way to fight the disease.
Other preventive methods used are certain types of chemotherapies which require giving a full treatment course to vulnerable populations, but they only suppress stages of malaria to prevent serious organ failure.
However successful, all these treatments have a major weakness: the disease can come back again.
Drugs can prevent malaria, although with varying rates of efficiency. There are several factors responsible for this, including the inadequate or incomplete treatment of active infections, overuse of antimalarial drugs and, most importantly, the high level of genetic and metabolic adaptability of the parasites. Therefore, the best option to fight malaria would be to use a vaccine which can achieve better prevention and reduce the mortality of the disease.
Malaria vaccines have been under development since the 1960s and have faced many obstacles: the malarial parasites produce very complex antigens which made developing a vaccine very challenging. However, substantial development was made with the introduction of mRNA technology and genome sequencing.
There are today two vaccines for malaria, one of which – RTS,S, also known as MosquirixTM – was approved by the WHO a year ago and is currently being used in pilot programs across high-risk areas. The vaccine was first created in 1987 but due to the lack of available technological capabilities and insufficient knowledge about the protein structures, the vaccine was endorsed by the WHO for “broad use” in children only in October 2021.
The vaccine is made as a two-vial formulation: one of the vials is the lyophilised antigen (RTS, S) which must be reconstituted with the second vial containing the Adjuvant System (AS01) in liquid form. The lyophilised antigen is thermostable, whereas the liquid part is temperature-sensitive and can get hydrolysed (broken down by a chemical reaction with water). Therefore, MosquirixTM requires a storage temperature between 2°C and 8°C, failure of which may damage the antigen and/or adjuvant and reduce the vaccine’s efficacy or safety.
The second one (R21/Matrix MTM) is made up of fusion proteins and the Matrix MTM adjuvant which stimulates the recipient’s immune response toward the vaccine. It has not yet been approved by the WHO but has shown an efficacy of around 77% in over 12 months of trials in Burkina Faso, a country where malaria killed more than 4 million people in 2019.
Advantages of this vaccine over MosquirixTM would include the lower antigen dose required and higher efficacy. This is also a two-vial vaccine and it comprises the R21 protein, which is highly temperature sensitive and needs to be stored at -80⁰C, on one side and the Matrix MTM adjuvant which, on top of needing to be stored at temperatures between 2°C and 8°C, is also photosensitive.
One of the major challenges facing the proper use of these vaccines is the inaccuracies in the logistics currently in place around them. Because of how temperature-sensitive the various parts of these vaccines can be for their safe administration, they need to be transported and stored reliably at low temperatures. Therefore, having the necessary cold chain to maintain these vaccines at their optimal conditions is crucial.
Extremely critical packaging, transport and distribution conditions
“Long-term storage and delivery of vaccines are vital, especially as governments seek to vaccinate rural and remote communities. This requires cold chain infrastructure investments, workforce training and, very importantly, last mile coordination.” warns Luc Provost, CEO of B Medical Systems. “It is challenging for pharmaceutical companies to create thermostable vaccines since biological molecules in aqueous solutions are inherently unstable. However, this creates a severe issue for areas with high ambient temperatures where maintaining a protective cold chain is challenging because of a lack of infrastructure. The lack of proper cold chain systems can lead to a reduction in the potency and therefore efficacy of the vaccines,” he adds.
Cold chain disruptions can occur due to several reasons such as the use of outdated or improperly managed refrigerators and freezers, sudden blackout due to an unreliable electricity infrastructure, or just poor compliance with cold chain procedures. Therefore, it is very important to use medical cold chain solutions whose parameters and effectiveness can be tracked and controlled, as well as systems that can operate effectively in regions with unreliable power supplies for long periods of time while maintaining the required temperatures. “Temperature variations inside the freezers or transport boxes need to be monitored to prevent any risk as temperature variations could lead to the denaturation and spoilage of all biological products stored inside. That simply cannot happen. Ruining a stock of vaccines will not only cost a lot of money, but it could ultimately lead to deaths.” Provost points out. “In tropical countries, the difference in temperatures between the inside and the outside of a freezer can reach 120°C. It is therefore crucial to use cold chain solutions specifically designed for such extremes, and to equip them with the needed optional accessories such as independent power supplies, localization systems and alarms.” Provost concludes.
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