The announcement of a room temperature stable mRNA vaccine candidate by COVID-19 vaccine researchers suggests this advance might, potentially, revolutionize the entire field of vaccine production. This development opens the way to overcome at least one crucial obstacle that has made vaccines inaccessible, particularly, to under-developed nations and in remote areas within even developed countries. Work to develop a worldwide vaccine naturally includes China, which also continues an active collaboration with nations in Africa, Latin American and the Caribbean to alleviate, and ultimately eradicate poverty. This latest mRNA vaccine development is a product of Beijing Institute of Microbiology & Epidemiology, and other key medical institutions in China.
Vaccines tend to be sensitive to both heat and cold. This matter is one of great concern in the transport and storing of vaccines to guard against the loss of a vaccine’s stability, especially preventing loss of characteristics that make it safe and effective for use.
The paper, “A thermo[-]stable mRNA vaccine against COVID-19,” published in the journal Cell, evaluates the thermal stability of the mRNA- LNP (lipid-nanoparticle) vaccine candidate named ARCoV. Researchers stored the vaccine at various temperatures for one, four, or seven days, injected it into the animals, and used a bioluminescence technique to visualize its tissue distribution at various sites: intramuscular lymph nodes, the liver in vivo and ex vivo. These results showed the vaccine delivery to be effective and that it achieved the same high level of neutralizing antibody expression after being stored at room temperature for one week, without any signs of decreased activity.
The final vaccine is to be manufactured in a “ready-to-use” and thermo-stable, single dose liquid formulation in a pre-filled syringe, without the need of thawing or reconstitution before injection.
Unlike other conventional forms of vaccine, which need “cold-chain transportation,” the ARCoV vaccine is desirable because it eliminates this requirement.
Discussions in the paper note that ARCoV is the first in vivo evaluated mRNA vaccine candidate, where pre-clinical study is performed in mice and large animals (monkeys or non-human primates), which overcomes temperature sensitivity, [and ] demonstrates “immunogenicity and protection against SARS-CoV-2 [virus causing COVID-19] in animal models, which supports further clinical development in humans.”
Although ARCoV is designed on an mRNA vaccine platform, it differs, fundamentally, from Moderna’s mRNA 1273 vaccine. Firstly, ARCoV is room-temperature stable. Another key difference from Moderna’s vaccine is the antigen region researchers chose as ARCoV’s target.
The in vivo study targets the ‘Receptor-Binding Domain’ (RBD) as the antigen target. The RBD which lies on the antigen’s surface affords an extremely accessible target. The researchers state that this target area “may induce fewer non-neutralizing antibodies which lowers the risk of ADE [antibody-dependent enhancement] a type of SARS-CoV-2 infection,” a phenomenon seen during coronavirus infection.
The researchers caution, however, that “…the duration of neutralization antibody induced by ARCoV is yet to be determined, as experience from other human coronaviruses has indicated the possibility of re-infection due to waning of the antibody response…”
“A thermostable mRNA vaccine against COVID-19.’ Zhang N-N, et al. Cell, 2020 doi: https://doi.org/10.1016/j.cell.2020.07.024
“Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine.” Tai W,et al. Cellular & Molecular Immunology, 2020 https://doi.org/10.1038/s41423-020-0400-4
“The coding sequence of firefly luciferase reporter gene affects specific hyperexpression in Arabidopsis thaliana cpl1 mutant.” Koiwaa, b H. and Fukudomeb A. Plant Signaling & Behavior , 2017 doi: 10.1080/15592324.2017.1346767
How do Vaccines Work?
The primary function of the immune system is to fight off foreign invaders in the body. [The immune system includes organs, such as the skin, spleen, lymph nodes, tonsils, etc; cells: white blood cells, T Cells, B cells which produce antibodies, macrophages can engulf and enclose foreign invaders to destroy them; molecules, such as anti-microbial peptides, oxidative enzymes, clottable protein, pattern recognition proteins, etc.]
When injected into the body, a vaccine disguises itself to appear (to the immune system) as a foreign invader, but does NOT make the body sick.
Vaccination exposes the body to substances called antigens, which are similar to those found on the surface of foreign agents. Posing as a specific invader, a vaccine signals the immune system to respond, swiftly and robustly, if ever it encounters such an invader.
Here is a simplification of the Response to Vaccine process.
Antigen-Presenting Cells (APC) circulate in the body looking for foreign invaders. When an APC finds a vaccine-imposter invader [antigen], it ingests the invader, breaks it apart and displays a piece of the antigen on its own surface. This APC [displaying a piece of the antigen] circulates to places in the body where there are clusters of immune cells, such as lymph nodes.
Another kind of immune system cell, called Näive T Cells, which are sensitive to the antigen recognize it as an invader and become activated. Nearby, other immune system cells – “T Helper Cells” send out signals which also announce the invader’s presence. Näïve B Cells also may react to the vaccine- imposter [antigen]. B Cells can recognize antigens displayed on Antigen-Presenting Cells (APC) as well as react to antigens roaming freely in the body.
Active B Cells may divide and produce more B Cells specific to the vaccine’s imposter antigen. Some of these B Cells will mature into plasma B cells, and others will develop into memory B cells. The transformed plasma B cells act as the immune system’s antibody production sites, which produce antibodies specific to the vaccine imposter antigen.
Plasma B Cells secrete antibodies, which are “Y” -shaped proteins released at high levels every second. In the body there are hundreds of millions of different type antibodies. The wide availability of these antibodies allows them to interact and bind with a huge range of antigen.
Each antibody binds to one specific, target antigen, which closely fits as a lock and key does. This action may prevent the antigen from entering a cell or mark the antigen to be destroyed.
Attenuated virus – Some vaccines use weakened forms of a virus, called attenuated virus, to stimulate an immune response and cause immunity without causing sickness.
mRNA – is an abbreviation for messenger RNA, a single-stranded substance, derived from RNA, that is complementary to one of the DNA strands of genetic material. RNA vaccines use a different approach that take advantage of the process that cells use to make proteins: cells use DNA as the template to make messenger RNA (mRNA) a substance that then translates into building proteins. An RNA vaccine consists of an mRNA strand that codes for a disease-specific antigen. Once the mRNA strand in the vaccine is inside the body’s cells, the cells use the genetic material to produce the antigen. This antigen is then displayed on the cell surface, where it is recognized by the immune system.