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Frontrunner vaccines, which one?

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An old nursery rhyme makes a lot of speculations that even the Joint Admissions and Matriculation Board (JAMB) examining body will not dare speculate about. The rhyme makes conjectures like “If all the seas were one sea, what a great sea that would be. If all the trees were one tree, what a great tree that would be.” The poem goes on in its postulations and wonders if all of humanity was one man and he took an amalgamation of all the axes in the world to chop down a globally coalesced tree, what kind of splash will it make in the merged seas.

These are all iffy speculations that a lot of permutations and combinations will not give a definitive answer. Similarly, in this COVID-19 era, we have a lot of vaccine skepticism that do not come with clear answers even though the questions surrounding them are more valid than musings about if all the seas were one sea.

A few weeks ago, countries from the European Union, the USA and several countries began immunizing their citizens. BioNTech-Pfizer and Moderna vaccines were the first two vaccines to receive emergency authorization in the United Kingdom, European Union and the USA. AstraZeneca-Oxford recently received emergency authorization from the UK adding to the bulging arsenal that it now has against the virus. Meanwhile, low-income countries are left grappling for leftovers. The UK has ordered for a total of 367 million doses of vaccines for its population of just 68 million. Canada has ordered for vaccines that could immunize more than 500 percent of its population. What types of frontrunner vaccines do we have? Are there advantages or disadvantages? I wrote about three of these frontrunner vaccines in a previous article in The Guardian, titled Three Promising Vaccines; What Next?

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BioNTech-Pfizer and Moderna vaccines are both messenger RNA vaccines. Messenger RNA vaccines have never been used on humans before. When either of these two messenger RNA vaccines are injected into the human body, they instruct the cells to produce a protein that is the same as the spike protein on the coronavirus. These newly produced spike proteins are not infectious but the body recognizes them as foreign bodies or antigens and produces its own antibodies to neutralize them. In addition, the body produces memory cells in case of future attacks by an actual virus. Messenger vaccines are quicker to produce but need to be stored at very low temperatures because of the very fragile RNA. Therefore, the Moderna vaccine must be stored at minus twenty degrees Celsius while the BioNTech-Pfizer vaccine must be stored at minus seventy degrees Celsius. Moderna vaccine costs $33 each while the BioNTech-Pfizer vaccine costs $20. The Moderna and BioNTech-Pfizer vaccines are two-dose vaccines.

Apart from messenger RNA vaccines, there are other vaccines types. The non-replicating viral vaccine vector is another type. AstraZeneca-Oxford vaccine is a traditional vaccine type made by injecting an inactivated form of a chimpanzee common cold virus, also known as chimpanzee adenovirus. The chimpanzee adenovirus is a vector. It is the vector that is carrying the DNA or genetic material with instructions to make a non-infectious spike protein. It is better to use the chimpanzee common cold virus because about eighty per cent of humans already have a high proportion of antibodies against the human common cold viruses (Ad5) and this pre-existing immunity may destroy the human common cold virus if it was used. If it does, the DNA instruction it is carrying will not reach the cells. However, only about one per cent of humans have antibodies against the chimpanzee common cold virus, which makes it a good vector.

The human body recognizes this harmless spike protein as an antigen and produces antibodies. It also produces memory cells that will memorize the antigen in case of future infections. The adenovirus vector also elicits an immune response, thus the immune response from adenoviral vector vaccine type is strong. Adenoviral vectors have been used since early 2000s and have been used to develop experimental vaccines against AIDS, malaria, tuberculosis and Middle East Respiratory Syndrome (MERS). Viral vectors have also been used in gene therapy, anticancer treatments and in vaccine development.

Other pharmaceutical companies that have produced vaccines through virus vectors like the AstraZeneca-Oxford are CanSino Biological Incorporation, Johnson and Johnson and Gamaleya Research Institute (Sputnik V from Russia). CanSinoBIO vaccine and the Johnson and Johnson vaccines are single dose vaccines while the AstraZeneca-Oxford and Sputnik V are two-dose vaccines. These three vaccines can be stored in a standard refrigerator at 2-8 degrees.

The CanSinoBIO vaccine is from China. It uses the human adenovirus serotype 5 (Ad5). Phase 2 clinical trial results showed that more than half of the volunteers already had immunity against the Ad5 especially the elderly so CanSinoBIO vaccine may not work well in elderly patients.

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Johnson and Johnson vaccine uses a rarer human adenovirus subtype, Ad26. However, the snag with Johnson and Johnson vaccine is that while antibodies to Ad26 are uncommon amongst people living in USA and Europe, they are eighty to ninety percent present amongst those living in sub-Saharan Africa, which poses a challenge if we intend to use it in Nigeria.

The Sputnik V uses the Ad26 human adenovirus in the first vaccine dose and Ad5 human adenovirus Ad5 in the second dose. The idea of using two different human adenoviruses is to circumvent the antibodies that could have been produced against the vector human adenovirus used in the first dose. The immunity boost produced by using two vector adenoviruses is much higher than the immunity boost from vaccines that use the same adenovirus vector in first and second doses like AstraZeneca-Oxford vaccine. Sputnik V is the only adenovirus vector vaccine that has used two vectors.

The AstraZeneca-Oxford costs about four dollars for a dose while the Sputnik V costs ten dollars per dose. Sputnik V has been approved in Algeria, Argentina, Bolivia, Serbia, Belarus and Russia. More than 1.5 million people have received the Sputnik V vaccine including Putin’s daughter. The earliest emergency approval for the Johnson and Johnson vaccine is likely to be from Britain. It is undergoing phase three clinical trials in most of the Latin American countries where the confirmed coronavirus cases are extremely high. The AstraZeneca-Oxford vaccine has received approval from the UK and Mexico. The USA, Canada and European Union are yet to give approval.

Another set of vaccine type that is a frontrunner is the inactivated coronavirus vaccine. These are the CoronaVac (SinoVac) and Sinopharm vaccines. The SinoVac company developed the CoronaVac vaccine while the Sinopharm/Beijing Institute of Biological Products developed the Sinopharm. These two vaccines were developed in China. Inactivated virus vaccines have been in use for about 50 years. The polio vaccine injection given in the arm or leg is an inactivated virus. (The oral polio vaccine is a live one.) Some flu vaccines are from inactivated viruses.

In November last year, the Prime Minister of United Arab Emirates got vaccinated with the Sinopharm vaccine. The inactivated coronavirus particles stimulate the immune system. The genetic material in the coronavirus has been inactivated and can no longer replicate but the spikes remain intact. The CoronaVac vaccines can be stored in a standard refrigerator between 2 and 8 degrees Celsius.

Importantly, an inactivated coronavirus vaccine can theoretically trigger an enhanced respiratory response from Antibody Dependent Enhancement (ADE) of infection. It has not been reported in any of the clinical trials with an inactivated coronavirus though data on phase three of the clinical trials have not been shared publicly. If a vaccinated person gets coronavirus infection, the body can make the wrong antibodies and form immune complexes which can end up clogging the lungs. Another downside to the inactivated virus vaccine is that manufacturers would have to keep viable and large portions of the coronaviruses in their laboratories before killing them, posing a danger of accidental release. Further, it takes a long time to manufacture inactivated vaccines.

So far, I have described several frontrunner vaccines; messenger RNA vaccines, adenovirus vector vaccines and the inactivated coronavirus vaccines. If we were to choose vaccines, which would we choose?

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The messenger RNA vaccines are fragile and need to be kept at very low temperatures. Even if we procure these RNA vaccines, and keep them in freezers at the right temperature, how can we get them to consumers across all the states? What about electric power failures? Apart from being expensive to maintain, they are costly.

All the adenovirus vector vaccines can be kept in a standard refrigerator and are cheaper than the messenger RNA vaccine types. Adenovirus vaccines have been used on humans before unlike messenger RNA vaccines. Adenovirus vaccines are affordable and give a strong immune response. If choosing a human adenovirus vaccine vector, human adenovirus serotype Ad26 is suitable for those living in sub-Saharan Africa. Sputnik V and AstraZeneca-Oxford fits the table for Nigeria.

Inactivated vaccine types have also been used on humans before but carry some theoretical risks in the production and post-injection. Inactivated coronavirus vaccine types from China can be stored at standard refrigerator temperature making it easy for easy transportation and storage. They were clinically trialed in the United Arab Emirates with thirty-one thousand volunteers involving 125 nationalities. The Sinopharm and SinoVac vaccines would theoretically be good but their data has not been shared publicly so there are unanswered questions.

If you’ve had a natural COVID-19 infection before, you should still get vaccinated because you don’t know how long the immunity will last. There will always be iffy questions around vaccines but while waiting for answers we can keep safe by keeping all the COVID-19 protocols.
Obilade, Associate Professor of Public Health at Nile University of Nigeria, Abuja.
Obilade, an associate professor of public health is of College of Health Sciences, Nile University, Abuja.

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