The immune response against viruses consists of a series of cascading events that escalate if the body is unable to control the infection quickly.
First, the innate immune system is mobilized, whose main representatives are macrophages, which develop the same type of response regardless of the infectious agent. If it is not enough to kill the pathogen, the adaptive or acquired immune system is mobilized, much more sophisticated and dependent on the type of bacteria or virus. The protagonists of the adaptive immune response are lymphocytes, capable of generating antibodies and immune memory.
Once a person has passed an infection, approximately 100 memory lymphocytes remain in their body, which will roam in the blood and organs, immediately developing a specific immune response if the person is attacked by the same pathogen again. These memory cells die with age, more rapidly if the person is subjected to stress or chronic diseases.
Halfway between innate and acquired immunity are two types of immune cells: gammadelta (γδ) and Natural Killer or NK. Although these cells are nonspecific and capable of responding to any attacker, they can develop memory regarding the pathogens they have attacked. Macrophages, γδ and NK do not recognize a specific protein of the pathogen, but rather molecular patterns of cell damage or stress. On the contrary, lymphocytes respond to a certain protein of the pathogen. In human beings there is a preponderance of the innate immune system in children (who have not yet developed adaptive immunity) and the elderly (in whom it is “dying out”).
In this regard, a vaccine developed against a specific protein of a virus should generate a more robust immune response in young people and adults, while a vaccine against the complete virus could be more effective in children and the elderly.
Better to contribute than compete
As of June 16, 2020, the portfolio of vaccines in development against COVID-19 is 16 3, being in different stages of development. Most of these vaccines have used one of the strategies shown in the following figure.
At this moment 10 vaccines are being tested in clinical phases. The requirements of each of the phases (in the following figure) guarantee the efficacy and safety of the candidates and are regulated by EMA, WHO and FDA regulations.
One of the most advanced is that of Moderna, based on the messenger RNA that produces the spike (S) protein of SARS-CoV-2, responsible for entering our cells by binding to the ACE-2 receptor (a angiotensin 2).
Another vaccine is the one developed by the University of Oxford, ChAdOx1 nCoV-19. This vaccine uses an attenuated version of a virus that is not harmful to humans but causes infections in chimpanzees, and has been genetically modified to produce the S protein of the coronavirus.
Cansino Biological is developing a vaccine similar to the previous one, AD5-nCoV, which uses a non-replicating virus that causes the common cold. This vector carries the gene for the protein S from the surface of the coronavirus, with which it is tried to provoke the immune response to fight the infection.
Lastly, Sinovac Biotech is developing the PiCoVacc vaccine, which uses the chemically inactivated SARS-CoV-2 virus.
Why we need a shared podium
In light of the above, the enormous effort by researchers and pharmaceutical companies to find an effective vaccine against COVID-19 should not be a race with only one winner.
The development of the disease itself, shared by other SARS, causes an exaggerated enhancement of the immune response in individuals with a weakened or less efficient immune system (prevalence of innate response). However, a vaccine, to be effective for a long time, must develop an adaptive response in the body, mostly that generated in adults, not the elderly.
For this reason, the range of vaccines that will be available in the future will be able to cover different degrees of efficacy and will allow for sufficient group immunity to minimize transmission and protect the most vulnerable.
The best vaccine should protect healthcare personnel, adults with comorbidities, be effective for children and the elderly, minimizing the immunoenhancing effect, and fast and easy to produce and store. Having several options with different specificities will allow to administer the most appropriate according to the individual and situation.
Factors such as seasonality and geographic, health and social diversity have influenced the incidence of the disease and, logically, will affect the prophylaxis strategy.
In tropical countries it would be mass vaccinated to protect the most vulnerable population. However, in countries with temperate climates, with seasonal incidence, the population most at risk would be immunized in periods of low transmission, as occurs with the annual campaign against influenza.
Therefore, we will need all the candidate vaccines that cross the finish line, and be prepared for the new challenges that, in global health, remain to come.
By: María Mercedes Jiménez Sarmiento (Senior Scientist. Systems Biochemistry of the bacterial division. Scientific communicator. Margarita Salas Biological Research Center CIB – CSIC); Matilde Cañelles López Researcher (Scientist, Science, Technology and Society group, Institute of Philosophy, IFS-CSIC); Nuria Eugenia Campillo (Senior Scientist. Medicinal Chemistry, Center for Biological Research Margarita Salas CIB – CSIC)
The authors participate in the BIFISO project, PIE CSIC-COV19-027, funded by the CSIC, for the fight against COVID-19 within the framework of the Global Health PTI.
This article was originally published on The Conversation. Read the original.
