The first association that comes to mind when thinking
about vaccination is Louis Pasteur and his rabies vaccine. However, Manchu
elites have been practicing variolation since the 17th century by
inserting pus in their nose, provided from sick patients with smallpox. This
method was not well spread in China and unknown from the rest of the world. An
English doctor from the 18th century, Edward Jenner, has discovered
and spread this approach in Europe. Indeed, he found that the farmers had
dampen symptoms of smallpox. Cows, vacca in latin, are infected with
cowpox and when milking, farmers are exposed to the disease but have shown only
small pimples. Jenner took all bets and chose to inoculate a child with the pus
from a farmer’s pimple. Three months later he directly injected the smallpox
virus (also called vaccine) into the child, who showed no symptoms at all: he
had been vaccinated. Nowadays, numbers of vaccination approaches have been developed
and vaccination is a major stake for public health.
Vaccination,
an altruism action
The World Health Organization describes
vaccination as “the administration of agent-specific, but safe, antigenic
components that, in vaccinated individuals, can induce protective immunity
against the corresponding infectious agent.” The goal is to protect someone
from a disease by triggering his immune system, without inducing excessive symptoms.
Vaccination, though, is not only an individual procedure but also a collective protection.
One should picture the vaccine as a body armor, a flak jacket, and the
infection as a bullet. When several people wear a flak jacket, a fence can be
built such as a safety gate, which will provide a blanket security for the unvaccinated
and vulnerable persons. This phenomenon is called the herd immunity.

Figure 1: Herd immunity explanatory
scheme (Source: Herd Immunity - National Health Institute.)
Herd immunity is dependent on vaccination
coverage which is equivalent to the proportion of people vaccinated at any
given time. However, the percentage of people who must have antibodies to
achieve herd immunity to a given disease depends on each disease. For example,
mumps is a disease for which the immunization coverage is 90% and the group
immunity threshold is 87%. Consequently, the disease has almost disappeared
from the territory. Conversely, for measles, which is extremely contagious, the
threshold of immunity is 95% while vaccination coverage is only 90%. In other
words, for group immunity to be effective, 95% of the population must have
antibodies but only 90% people are vaccinated. Thus, the barrier formed by
vaccinated people has flaws. This is why, between 2008 and 2012, there was a
surge of measles cases in France and unvaccinated people were struck by stray
bullets. In comparison, the group immunity threshold to be achieved for the
population to be protected from Covid-19 disease is 50% to 60%. In terms of R0,
which means the number of people infected by a single person carrying the virus
in a non-immune population (the red circles in figure 1), the Covid-19 disease
is between 2 and 3 while the R0 for measles is between 12 and 18. A
well-applied vaccination strategy can achieve disease eradication and this has
been proven with the global smallpox disease vaccination strategy which has
been successful, since it disappeared in 1980.

Figure 2: Potential evolution of a
vaccine program (Source:
https://vaccinclic.com/index.php/100-la-vaccination/55-epidemiologie-vaccinale)
Different
vaccine types
There are two main areas of
vaccination: preventive vaccines, the most common, and therapeutic vaccines. Preventive vaccines are
the vaccines we talk about most often and which aim to trigger an immune
reaction in order to set up a cellular memory to prevent reinfection by a
pathogen. Therapeutic vaccines do not work against an infection, but against a
disease such as cancer, for example. There are different families of vaccines. Live-attenuated
vaccines are pathogens that are alive but whose virulence,
that is, the ability of the germ to grow and produce toxins, is reduced and
attenuated. It's the equivalent of a plastic ball pistol projectile. When you
get hit you feel a little pain and you might get a bruise, but nothing serious
compared to a real gunshot wound. Inactivated
vaccines contain pathogens that have been killed by heat or
chemical processes. Here, the projectile can be likened to a harmless foam
bullet.
Subunit vaccines are fragments of the pathogen that have been isolated. For
example, toxins of bacterial origin will be injected. In this case, we have in
our hands a fragment of a bullet and we will be able to do ballistics to set up
protection against the pathogen. Last but not least, genetically modified
vaccines, such as RNA vaccines, where an antigen of the pathogen will be
expressed by being produced by our own cells. In this case, our body will
itself manufacture the projectile in order to be able to analyze it and study
it to create a suitable bulletproof vest.

Figure 3: Different
vaccine types (Source: Adapté de Nature Materials, 19, 810-812, 2020)

Figure
4: DNA or RNA vaccines mechanisms (Source:
https://www.scienceaujourlejour.fr/pages/coronavirus-de-wuhan/la-course-aux-vaccins.html)
Another
important point to emphasize is the role of adjuvants. They are used in
conventional vaccines to increase the immune response and cell memory. It
ensures efficacy in the case of less immunogenic vaccines such as subunit
vaccines. The latter, poorly immunogenic, are used for example on elderly and
immunodeficient people who are fragilized. These subjects cannot be put in
contact with a strongly immunogenic vaccine, based on an attenuated virus for
example, so as not to risk uncontrolled infection. To overcome the poorly
immunogenic nature of the vaccine, an adjuvant is added which will strengthen
the inflammatory response.
Vaccination
is a major breakthrough in the medical field and has eradicated many diseases. Its
advantages lie in the individual prospect but also in the greater good. Despite
the improvements made in this area, many are still reluctant to be vaccinated. However,
it remains the most suitable solution to counter pandemics. This is currently
the case with the coronavirus crisis. Technological advances allow innovations
in the creation of vaccines and in particular with RNA vaccines. Many
biotechnology companies are turning to this type of vaccine because it avoids
the direct injection of infectious agents, unlike conventional vaccines, and
their production cost is low. Moreover, unlike the DNA vaccine, we will not
have the risk of creating mutations by integrating vaccine information. The
major problem with this vaccine is that RNA is very fragile because it is
naturally the target of degrading enzymes (see Tatiana Grouin’s paper). It must
therefore be encapsulated in order to be delivered inside the cells and must
also be stored at very low temperature. Despite those necessities, RNA vaccines
are very promising and are awaiting approval for other viruses such as Zika
virus.
Paper written by Anne Clerico
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