PART 3: The Development Path Of Modern Viral Vaccine Technologies
The development of vaccines has been a deliberate human effort that began in 1796 when Edward Jenner developed the smallpox vaccine.
Vaccine technologies have since evolved, but the principle behind the concept remains the same. A vaccine comprises parts of a pathogen (the antigen) that will interact with your immune system to trigger an antibody response. It typically will be administered prophylactically before infection. In case of future infection, your body will be ready to defend itself. Vaccines can also be used therapeutically as is the case in some experimental cancer medicines.
Just to recap, in Part 1, I raised an alert about what seems to be emerging public hesitation to vaccination. In Part 2, I discussed the origins of vaccination as a concept of preventive medicine. We also saw how smallpox was eventually eradicated through concerted vaccination efforts.
In this part we?ll get to see the transitions in the development of virus vaccine technologies.
Historically, vaccines have managed some of the worst contagious infections mankind has ever encountered. But vaccine technology is not a singular technology.
First-generation virus vaccines are those that were manufactured pre-1900. They were live attenuated viruses cultivated in animals. Smallpox and rabies vaccines were selected through multiple rounds of production. Weakened and less virulent forms were to be identified. These vaccines could emulate the infection process without causing severe disease. During this time, vaccines comprised whole organisms. They had high ability to stimulate innate immunity and induce long-term protection.
Second-generation virus vaccine technologies ran from 1900 to 1950. Yellow fever virus and influenza vaccines were raised in embryonated chicken eggs. They were prepared either as live attenuated or inactivated vaccines, where the pathogen was killed. These vaccines were also administered as whole organisms.
From 1950 to 1970, a third generation virus vaccine technology emerged. Viruses were isolated in cultured cells in laboratories. The focus shifted to polio, measles, mumps and rubella viruses. Humans are the only known host of these four viruses, which remain on the WHO radar for elimination and subsequent eradication.
It is important to note that the emergence of new virus vaccine technologies does not necessarily mean the erasure of previous technologies. It?s a continuum approach to building a repository of techniques. All these technologies still exist today and many vaccines are still made the same way.
Moving on ?
Fourth-generation virus vaccine technologies emerged between 1980 and 1990. For the first time a whole organism was not required to generate the antigen. Recombinant DNA technology allowed scientists to focus only on the immunogenic parts of the viruses. Vaccines were no longer infectious material; they were just recombinant protein molecules expressed in a laboratory. The purified proteins were then stabilized into an active formulation. A notable success story out of this era is the hepatitis B subunit vaccine.
From 1990 up to 2019, fifth-generation virus vaccine technologies were developed. For the first time, the vaccine administered was not a protein. The vaccine molecule was a genetically engineered DNA vector, itself not directly immunogenic. It carries the antigen-coding sequence that the cellular machinery will read to express proteins that would then trigger an immune response. This technology has been used on a variety of modern viral infections with varied degrees of success.
In our bodies, at the cellular level, DNA is activated in a 2-step process. The encoded message is first transcribed into a messenger RNA (mRNA) in the nucleus. The mRNA is exported from the nucleus to the cytoplasm where it is then translated into proteins by ribosomes. These proteins must exit the cell to be recognized by the immune system.
Today, I feel confident to write that we have sixth generation virus vaccines. These are the novel mRNA vaccines developed simultaneously but independently by Moderna and Pfizer/BioNTech.
What the novel mRNA vaccines have done is deliver the messenger directly to the ribosomes, skipping the whole DNA stage.
As a molecular virologist, I feel honoured to be alive to witness history; the beginnings of the adoption of this new technology. I can?t wait to see what the future holds.
In a perfect world, a vaccine would have 100% efficacy. A 100% efficacy simply means that everyone who gets vaccinated becomes immunized and has zero risk of infection. In simple language, everyone gets immune to the target disease agent.
But what does vaccine efficacy actually mean?
Vaccine efficacy is a measure of the proportionate reduction in cases among vaccinated persons, relative to the unvaccinated. So a vaccine efficacy of 90% indicates a 90% reduction in the risk of getting the disease among the vaccinated group.
Unfortunately, no vaccine is 100% efficacious. Most vaccines developed usually have lower efficacy levels. Some vaccinated people do not get immunized. A small percentage of people are not protected after vaccination. Their immune systems just don?t build up the protective antibodies. And for others, the protection may wane over time. Also, some people are unable to be vaccinated due to pre-existing conditions such as allergies and immune suppression.
This should not cause concern for those affected. When enough of the population is immunized, herd immunity kicks in.
So what is herd immunity?
Herd immunity (also called community immunity) is typically required to stop the community spread of a contagious disease. When a large percentage of the population becomes immune to a disease, the larger community is protected. Herd immunity can slow down or stop disease transmission in the general population. If enough people are immune then transmission of the disease is reduced or eliminated.
SARS-CoV2 (the virus causing COVID-19) is highly contagious. Some epidemiologists suggest that herd immunity at a proportion close to 90% may be required to completely stop the transmission and community spread of SARS-CoV2. The suggested proportion is close to the herd immunity required to stop the transmission of measles virus; one of the most contagious diseases in the world.
This is where things get interesting
Both Moderna and Pfizer/BioNTech published data that suggested that their novel mRNA Vaccines had an efficacy in the range of 95%. This is a pretty impressive feat considering that they had worked under the pandemic pressure. With such high efficacy, if sufficient persons are vaccinated in the population and get immunized, protective herd immunity can easily be achieved for the majority without exposure to natural infection.
However, despite the promise, there are emerging concerns voiced by the public about these novel mRNA vaccines. In my opinion, such concerns must be addressed to build public confidence and trust.
In the fourth and final part of this article series, I?ll highlight the specific concerns.
If you missed the first two parts, you may find them below:
PART 2: Origins of Vaccination
PART 3: Generations of Vaccines
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