Vaccination: the bodyguard

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 17^th 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 18^th 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

References:

1. Abbas, A., Lichtman A. H., Pillai, S. Basic Immunology, Functions and disorders of the immune system, fourth edition. (2014).

2. Combadière, B. Immunité adaptative contre le virus SARS-CoV-2. Médecine/Sciences 36, 908–913 (2020).

3. Grassly, N. C., Kang, G. & Kampmann, B. Biological challenges to effective vaccines in the developing world. Philos. Trans. R. Soc. B Biol. Sci. 370, (2015).

4. Federica Sallusto1, Antonio Lanzavecchia1, 2, Koichi Araki3, and R. A. From Vaccines to Memory and Back. J. Immun. 33, 451–463 (2010).

5. Riel, D. Van & Wit, E. De. Next-generation vaccine platforms for COVID-19. Nat. Mater. 19, 810–812 (2020).

6. Zimmermann, P. Factors That Influence the Immune Response to Vaccination. Clin. Microbiol. Rev. 32, 1–50 (2019).

7. https://www.santepubliquefrance.fr/determinants-de-sante/vaccination/articles/qu-est-ce-que-la-couverture-vaccinale.

8. https://www.has-sante.fr/jcms/c_2742985/fr/vaccination.

9. https://solidarites-sante.gouv.fr/IMG/pdf/calendrier_vaccinal_29juin20.pdf.

10. https://www.santepubliquefrance.fr/determinants-de-sante/vaccination/donnees/#tabs.

11. https://www.inserm.fr/information-en-sante/dossiers-information/vaccins-et-vaccinations.

12. https://www.who.int/topics/vaccines/fr/.

13. https://www.franceinter.fr/societe/le-mot-vaccin.

14. http://euradio.fr/2020/07/09/les-epidemies-de-variole-en-chine-du-xviieme-au-xxeme-siecles/.

15. https://www.pasteur.fr/fr/institut-pasteur/notre-histoire.

16. Herd Immunity - National Health Institute.

17. https://www.scienceaujourlejour.fr/pages/coronavirus-de-wuhan/la-course-aux-vaccins.html.