The covid-19 pandemic is not an unexpected event for science; microbes are an existential threat to humanity and today the new coronavirus (SARS-CoV-2) recalls, through the painful route, how fragile we are against infectious agents. The world’s hope is in the development of a vaccine.
Despite encouraging – and propaganda – news of the advancement of several vaccine prototypes that may be available in the short term, it is foreseeable that in the best of cases they have low, short-term or even dangerous protection.
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This concern stems from the fact that creating, developing and producing vaccines is a complex challenge where there are no foolproof ways. or definitive universal formulas.
Factors such as purity, safety (inability to cause any damage or biological alterations in the individual), immunogenicity (ability to produce defenses), efficacy (protective capacity against the specific pathogen), number of doses and duration of immunity, in addition to costs Development and manufacturing, transportation, storage and application must be considered.
Added to this is the fact that microbes are cunning organisms in permanent evolution that have learned, as Albert Camus said in The Plague, to survive in hibernation or dormancy to outwit changes in the environment and our immune system.
Fortunately, the development of vaccines has been a successful strategy to prevent diseases caused by some microbial agents, such as smallpox.
At this historical moment it is appropriate to clarify the development of the different types of vaccines. Regardless of the method they occur, they are told ‘best vaccine candidates’ to the selection of killed or mutated pathogens – naturally or in the laboratory – their DNA or RNA, proteins or those parts of them that arouse a greater protective immune response in vaccinated individuals.
Depending on their obtaining process, there are biological or chemical vaccines.
In the first group are the vaccines of complete microorganisms, that use the complete pathogen to protect individuals.
There are two types in this group: the first is that of dead or inactivated microorganisms, in which the pathogen is killed through chemical or physical processes. The second, of live attenuated microorganisms, in which it is cultivated in vitro the pathogen so many successive times that it loses the ability to produce the disease, but not to induce defenses.
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These vaccines have many limitations. For example, not all pathogens are cultivable and not all microorganisms, by killing them, maintain the ability to generate defenses in vaccinated individuals. or they can be attenuated in successive crops.
Despite advances in molecular biology, the fragments of its genetic material to be removed or modified to decrease or eliminate its aggressiveness are still unknown. An example of a vaccine for dead microorganisms is whooping cough, and a vaccine with live attenuated microorganisms, polio.
These vaccines have many limitations
Biologicals also include subunit vaccines, which are based on fragments of DNA, RNA or proteins essential for the survival of the microorganism.
In this group subdivision begins with recombinant vaccines, in which the gene encoding the protein of interest is extracted from the DNA of the microbe in order to be inserted or cloned into a microorganism Non-pathogenic that reproduces very fast and is capable of producing the protein in great quantity, which is extracted and purified later.
Examples are hepatitis B and HPV. However, not all genes encoding the proteins of interest can be cloned.
A universal vaccine?
In the SARS-CoV-2 virus 81 genetic variants have been identified of which, according to Korber, 19 have a frequency greater than 0.3 percent in the more than 30,000 isolated viruses of this type, which gives them different biological characteristics, such as speed of reproduction, pathogenicity, geographic distribution and synergy with other mutants that lead to very different clinical, pathological and epidemiological characteristics.
Recombinant vaccines against this virus must consider its genetic variability and that of humans.; in this interaction they could induce undesirable immune responses, such as producing antibodies that help the virus infect cells to reproduce more quickly and efficiently, a phenomenon known as Antibody Dependant Enhancement (ADE) of infection, described for other viruses such as SARS, MERS, dengue, etc., or generate negative reactions such as the increase in vaccine-associated respiratory disease (VAERD), immunological silence (effective evasion mechanism), immunosuppression, etc.
Producing a recombinant SARS-CoV-2 vaccine is not an easy, quick, or risk-free task.
There are also the modified viral vectors, in which the gene of interest is inserted into a virus. that induces few human defenses like that of the chimpanzee adenovirus (ChAd), to use as a vaccine.
These reproduce in the individual without causing more or no harm, but some viruses cross-react with human viruses, limiting their use. Also, inserting the entire gene for the protein (such as SARS-CoV-2) includes the problems mentioned for recombinant proteins. This vaccine, developed and advertised by the University of Oxford, together with the pharmaceutical company AstraZeneca, has already been negotiated with Brazil to produce 30 million doses.
DNA or RNA vaccines In this type, the pure genetic material (DNA or RNA) of the pathogen that codes for the protein, together with its regulatory regions, is directly introduced; it is the same vaccinated individual who produces the protein of interest in their own cells. These vaccines have the same drawbacks as recombinants or viral vectors.
Producing a recombinant SARS-CoV-2 vaccine is not an easy task
Due to the simplicity of its production, this method, with wide media popularity, is the vaccine of the Moderna laboratory and the National Institute of Health of the USA (NIH), It received $ 500 million for its development and production, and has sold millions of doses.
Moderna announced on July 15 the start of phase three with 30,000 individuals, and phase 1 and phase 2 human studies began only 66 and 74 days, respectively, after the virus’s chemical structure was published.
Carbohydrate vaccines, poorly immunogenic, are also found in other studies and research projects., which must bind to a carrier protein. They are the pneumococcal and meningococcal vaccines.
On the other hand, there are vaccines based on synthetic peptides, developed by Fidic in Colombia at the atomic level.
This method pioneered the synthetic vaccine against malaria in 1986 and is developed, from start to finish, by chemical synthesis, since once the vital proteins for the survival of pathogens are determined, they can be synthesized into small fragments called peptides.
Once studied, it is known which are the truly relevant in the invasion, infection and survival., enabling its modification to be able to induce in people a total and specific immune response against this fragment of the pathogen proteins.
It is a functional approach in which the three-dimensional structure of approximately 600 peptides was determined, both native and modified, for use as components of the malaria vaccine.
Fidic has been able to deduce most of the physico-chemical, biological and mathematical rules for obtaining vaccines with protective efficiency 80-90 percent, because the genetic variability of different human ethnic groups prevents achieving 100 percent. It is not the same to vaccinate white, oriental, black individuals, etc.
The regions of the pathogens best recognized by the immune response of individuals are in turn the most variable in their composition; that is why it is said that the pathogen mutated, which is another variant or a new one.
By mutating, even in one of its components, microbes escape the previously induced immune response, and as new mutants of the pathogen are generated, vaccines lose effectiveness.
This explains the restricted protection of many vaccines, since they are always against the new mutant –or variant–, but not against the virus in general.
SARS-CoV-2 is an RNA virus with a very high mutation rate. The original strain that appeared in China, variant 614D, became a new genetic variant in Europe, called 614G, managing to spread faster and more aggressively, with higher morbidity and mortality than China; It is the same that we have in Colombia, according to the virologist of the University of Antioquia, professor María Teresa Rugeles, Ph. D.
Most developing vaccines will induce antibodies against a specific strain, opening the possibility of infection by another strain.
This has been described by others who found a short duration of the immune response, reinfection or outbreaks, etc.
It is good to inform Colombia about the tortuous way to go to obtain a fully effective vaccine; as well as the political, economic and social interests behind it and all the problems inherent in its use that can induce a universal well-being, or a catastrophe in world health.
MANUEL ELKIN PATARROYO
Prince of Asturias Award for Scientific and Technical Research, 1994
COLLABORATION OF MARÍA JULIANA CAICEDO
SPECIAL FOR THE TIME