Part 2 of three 
Apart from technical considerations, choosing which Covid-19 vaccine to procure and stockpile can be guided by attributes that may be peculiar to a brand or product in terms of availability, storage and handling capacity, efficacy rates, pricing, etc.

Availability is a function of many factors. One is technology (see below “How the Covid vaccines work;” source RAPS.org, wellhealth.com, gavi.org), which can influence the speed and scalability in the production process of a vaccine. Vaccines that have been developed in one country, say the US or China, but can be mass-produced in plants in other countries, will have better odds at meeting demand from many countries. One can also see that this factor can be a major determinant of cost, which can vary from one country to another.

When volume of production is less than that of demand, queuing would likely happen, where several other factors can come into play. Obviously, those who funded — such as the US, the UK and Chinese governments, as well as private philanthropies like the Bill and Melinda Gates Foundation, or Operation Warp Speed, a private-public partnership with the US government — the development and subsequent clinical trials of a particular vaccine would be at the front of that queue. A bidding process can be used as well, which can be both above board and underboard. The amount of money involved and the rush by which it needs to move is too enticing for ordinary mortals not to be attracted to it.

Storage and handling are equally important. These goods are highly sensitive to temperature that mishandling can easily lead to waste. We also note that almost all of these vaccines require at least two injections, from 21 to 28 days apart. This adds to the total operational workload in recording and monitoring.

On efficacy rates, public trust in regulatory agencies is such that any vaccine that has secured approval would be acceptable. If at all, performance in clinical trials should be of greater importance to the scientist who developed it than to the consuming public. What can make or unmake the vaccination program is government messaging that informs and inspires, rather than create perceptions of lack of transparency.

How the Covid vaccines work

1) Weakened or inactivated vaccines (Sinopharm, CoronaVac/Sinovac, Covaxin, Novavax)

a. Whole virus

Technology/Platform. Whole virus vaccines use a weakened (attenuated) or deactivated form of the pathogen that causes a disease to trigger protective immunity to it. They contain the whole or part of the disease-causing pathogen, but the type of immunity they trigger is slightly different. Both are tried and tested vaccination strategies, which form the basis of many existing vaccines — including those for yellow fever and measles (live attenuated vaccines), or seasonal influenza and hepatitis A (inactivated vaccines).  Growing live pathogens also means stringent precautions must be taken to avoid the virus escaping and making vaccine plant workers sick. Once large amounts of virus or bacteria have been grown, they must then be isolated, purified and attenuated or inactivated, depending on the vaccine. Each of these steps requires specific equipment, reagents, and stringent procedures to avoid, and check for, contamination, which can further increase costs.

b. Live attenuated vaccines

Technology/Platform. Live attenuated vaccines are derived from viruses that have been weakened under laboratory conditions, so that when injected they will infect cells and replicate but cause no or only very mild disease. Because these vaccines are simply weakened versions of natural pathogens, the immune system responds as it would to any other cellular invader, mobilizing a range of defenses against it, including killer T cells (which identify and destroy infected cells), helper T cells (which support antibody production) and antibody-producing B cells (which target pathogens lurking elsewhere in the body, e.g., the blood). This immune response continues until the virus is cleared from the body, meaning there is plenty of time for memory cells against the virus to develop.

Because of this, live attenuated vaccines can trigger an immune response which is almost as good as being exposed to the wild virus, but without falling ill.

Advantages/Disadvantages. Although produced with well-established technology and relatively simple to manufacture, live attenuated vaccines are not recommended for people with compromised immune systems. In rare cases, they may even trigger sickness or disease. They are also relatively temperature sensitive. Careful storage and handling are necessary.

However, one advantage of live virus vaccines is that they tend to provoke a very strong immune response that lasts a long time. It’s easier to design a one-shot vaccine using a live virus vaccine than with some other vaccine types.

These vaccines are also less likely to require the use of an additional adjuvant–an agent that improves the immune response (but which may also have its own risk of side effects).

To summarize:
– Well-established technology
– Strong immune response
– Immune response involves B cells and T cells
– Relatively simple to manufacture
– Unsuitable for people with compromised immune systems
­– May trigger disease in very rare cases
– Relatively temperature sensitive, so careful storage necessary

c. Inactivated vaccines

Technology/Platform. Inactivated vaccines contain viruses whose genetic material has been destroyed by heat, chemicals or radiation so they cannot infect cells and replicate but can still trigger an immune response.  They are made by killing the virus (or other type of pathogen, like a bacteria). Then the dead, or inactivated virus, is injected into the body.

Because the virus is dead, it can’t really infect you, even if you are someone that has an underlying problem with your immune system. But the immune system still gets activated and triggers the long-term immunological memory that helps protect you if you’re ever exposed in the future.

Advantages/Disadvantages. Inactivated virus vaccines are considered safer and more stable than live attenuated vaccines, and they can be given to people with compromised immune systems. But because they cannot infect cells, inactivated vaccines only stimulate antibody-mediated responses, and this response may be weaker and less long-lived. To overcome this problem, inactivated vaccines are often given alongside adjuvants (agents that stimulate the immune system) and booster doses may be required.

To summarize:
– Well-established technology
– Suitable for people with compromised immune systems
– No live components, so no risk of the vaccine triggering disease
– Relatively simple to manufacture
– Relatively stable
– Booster shots may be required

d. Protein subunit vaccines

Technology/Platform. Protein subunit vaccines include harmless pieces (spike protein) of the virus that cause Covid-19 instead of the entire germ. Once vaccinated, our immune system recognizes that the proteins don’t belong in the body and begins making T-lymphocytes and antibodies. If we are ever infected in the future, memory cells will recognize and fight the virus. These vaccines can’t cause any active infection, because they only contain a viral protein or group of proteins, not the full viral machinery needed for a virus to replicate. All subunit vaccines are made using living organisms, such as bacteria and yeast, which require substrates on which to grow them, and strict hygiene to avoid contamination with other organisms. This makes them more expensive to produce than chemically synthesized vaccines, such as RNA vaccines. The precise manufacturing method depends on the type of subunit vaccine being produced.

Disadvantages. A downside of this precision is that the antigens used to elicit an immune response may lack molecular structures called pathogen-associated molecular patterns which are common to a class of pathogens. These structures can be read by immune cells and recognized as danger signals, so their absence may result in a weaker immune response. Also, because the antigens do not infect cells, subunit vaccines mainly only trigger antibody-mediated immune responses. Again, this means the immune response may be weaker than with other types of vaccines. To overcome this problem, subunit vaccines are sometimes delivered alongside adjuvants (agents that stimulate the immune system) and booster doses may be required.

Advantages. One of the advantages of protein subunit vaccines is that they tend to cause fewer side effects than those that use whole viruses (as in weakened or inactivated virus vaccines).

Another advantage of the protein subunit vaccines is that they have been around longer than newer vaccine technologies. This means that their safety is better established overall.
However, protein subunit vaccines require the use of adjuvant to boost the immune response, which can have its own potential adverse effects. And their immunity may not be as long-lasting compared to vaccines that use the whole virus. Also, they may take longer to develop than vaccines using newer technologies. According to a New York Times article, Novavax’s vaccine (which uses sub-unit protein) would be easier to distribute and store than the vaccines from Pfizer-BioNTech and Moderna. While those vaccines have to be kept frozen, Novavax can stay stable for up to three months in a refrigerator.

To summarize:
– Well-established technology
– Suitable for people with compromised immune systems
­– No live components, so no risk of the vaccine triggering disease
– Relatively stable
– Relatively complex to manufacture
– Adjuvants and booster shots may be required
– Determining the best antigen combination takes time

2) Pfizer/BioNTech/Moderna

Technology/Platform. Nucleic acid vaccines use genetic material (DNA or RNA) from a disease-causing virus or bacterium (a pathogen) to stimulate an immune response against it. They provide instructions for making a specific protein from the pathogen, which the immune system will recognize as foreign (an antigen). Once inserted into host cells, this genetic material is read by the cell’s own protein-making machinery and used to manufacture antigens, which then trigger an immune response. This is a relatively new technology, and of all vaccines that have been developed using this technology, only Covid-19 vaccines have so far been approved for human use. RNA vaccines encode the antigen of interest in messenger RNA (mRNA) or self-amplifying RNA (saRNA) — molecular templates used by cellular factories to produce proteins. Because of its transitory nature, there is zero risk of it integrating with our own genetic material. The RNA can be injected by itself, encapsulated within nanoparticles (as Pfizer’s mRNA-based Covid vaccine is), or driven into cells using some of the same techniques being developed for DNA vaccines. Once the DNA or RNA is inside the cell and it starts producing antigens, these are then displayed on its surface, where they can be detected by the immune system, triggering a response. This response includes killer T cells, which seek out and destroy infected cells, as well as antibody-producing B cells and helper T cells, which support antibody production.

Advantages/Disadvantages. The advantages of such vaccines are that they are easy to make, and cheap. Since the antigen is produced inside our own cells and in large quantities, the immune reaction should be strong.

Once a pathogen’s genome has been sequenced, it is relatively quick and easy to design a vaccine against any of its proteins. For instance, Moderna’s RNA vaccine against Covid-19 entered clinical trials within two months of the SARS-CoV-2 genome being sequenced. This speed could be particularly important in the face of new emerging epidemics, pandemic pathogens or pathogens which are rapidly mutating.

Both DNA and RNA vaccines are relatively easy to produce, but the manufacturing process differs slightly between them. Once DNA encoding the antigen has been chemically synthesized, it is inserted into a bacterial plasmid with the help of specific enzymes — a relatively straightforward procedure. Multiple copies of the plasmid are then produced within giant vats of rapidly dividing bacteria, before being isolated and purified. RNA vaccines are easier to synthesize because this can be done chemically, from a template in the lab, without the need for any bacteria or cells. In both cases, vaccines for different antigens could be manufactured within the same facilities, further reducing costs. This is not possible for most conventional vaccines.

To summarize:
– Immune response involves B cells and T cells
– No live components, so no risk of the vaccine triggering disease
– Relatively easy to manufacture
– Some RNA vaccines require ultra-cold storage
– Never been licensed in humans
– Booster shots may be required

3) Viral Vector (AstraZeneca, Janssen, Sputnik V, EpiVacCorona)

Technology/Platform. Vector vaccines contain a weakened version of a live virus — a different virus than the one that causes Covid-19 — that has genetic material from the virus that causes Covid-19 inserted in it (this is called a viral vector). Once the viral vector is inside our cells, the genetic material gives cells instructions to make a protein that is unique to the virus that causes Covid-19. Using these instructions, our cells make copies of the protein. This prompts our bodies to build T-lymphocytes and B-lymphocytes that will remember how to fight that virus if we are infected in the future.

A major bottleneck for viral vector vaccine production is scalability. Traditionally, viral vectors are grown in cells that are attached to a substrate, rather than in free-floating cells – but this is difficult to do on a large scale. Suspension cell lines are now being developed, which would enable viral vectors to be grown in large bioreactors. Assembling the vector vaccine is also a complex process, involving multiple steps and components, each of which increases the risk of contamination. Extensive testing is therefore required after every step, increasing costs.

Advantages/Disadvantages. Viral vector-based vaccines differ from most conventional vaccines in that they don’t actually contain antigens, but rather use the body’s own cells to produce them. They do this by using a modified virus (the vector) to deliver genetic code for antigen, in the case of Covid-19 spike proteins found on the surface of the virus, into human cells. By infecting cells and instructing them to make large amounts of antigen, which then trigger an immune response, the vaccine mimics what happens during natural infection with certain pathogens – especially viruses. This has the advantage of triggering a strong cellular immune response by T cells as well the production of antibodies by B cells.
One challenge of this approach is that people may previously have been exposed to the virus vector and raise an immune response against it, reducing the effectiveness of the vaccine. Such “anti-vector immunity” also makes delivering a second dose of the vaccine challenging, assuming this is needed, unless this second dose is delivered using a different virus vector.

To summarize:
– Well-established technology
– Strong immune response
– Immune response involves B cells and T cells
– Previous exposure to the vector could reduce effectiveness

Relatively complex to manufacture



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