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Vaccines. History of these medical tools so effective against infectious diseases that can die of success

World opinion on vaccines is embroiled in a paradoxical situation. More and more scientific data demonstrate their excellent usefulness in preventing many infectious diseases that without vaccines would cause millions of deaths every year. However, there are more and more supposedly educated and informed people who oppose vaccines with fallacious arguments that lack a medical basis and are closer to the mystical beliefs of other times. Many of these people with this supposed ‘knowledge’, care little about general health because of an incomprehensible and absurd selfishness to try that their family and friends do not suffer and are inside a glass urn. They do not realize that Preventive Medicine is very important for the survival of our species and that infectious disease do not distinguish social classes, religions, political ideas or physical and psychological appearance from anyone. This post is an update of a previous reflection published in the blog Mikrobios. I hope you enjoy it and, above all, that it encourages discussion.

In 1980, World Health Organization gave us wonderful news: it declared that smallpox had been eradicated. The last smallpox patient was treated in Somalia in 1977. This severe disease had caused hundred millions of deaths! Smallpox vaccine had been directly responsible for this great success. Optimism permeated society and made people think that we would be able to eradicate many other infectious diseases with vaccines. Time and a large heterogeneous group of people who have opposed the use of vaccines, some deliberately out of spurious interests, others out of ignorance, are moving us away from this essential objective. In some cases, such as measles, poliomyelitis or diphtheria, are leading us to dangerous and undesirable medical scenarios. A kind of return to the past where death caused by infections was very common.

Jonas Salk at the University of Pittsburgh where he developed the first Polio vaccine

In 1796, before the viral aetiology of smallpox was known, Edward Jenner  spoke with a milker who did not suffer from the disease because she had a mild skin infection, cowpox. He sensed its protective effect and began inoculating smallpox vaccine lesion material onto the skin of healthy volunteers (scarification). They developed a mild disease that gave them lasting protection (immunity) against human smallpox. Vaccine and vaccination names were coined by Louis Pasteur in honour of Jenner. However, smallpox immunization was practiced many centuries earlier in China. Chinese doctors had used dried and ground scabs from patients with mild smallpox to obtain a fine powder to protect healthy, non-immune people who inhaled it. Mary Wortley Montagu had observed in 1717 how in Turkey there were women dedicated to inoculating healthy people with fluids from smallpox lesions. Variolisation was very common in Europe because although it was associated with 2% mortality, it was significantly lower than that caused by smallpox (50%).

Over the last few centuries, vaccines, along with hygiene, water purification and antibiotics, have reduced infant mortality and increased life expectancy and quality of life. Vaccines save millions of lives each year. However, infectious diseases are still the leading cause of death in many poor countries where two out of three children under five die from digestive and respiratory infections that could be prevented by vaccination. Global efforts are underway to eradicate other diseases, such as polio and measles. However, these objectives have not been achieved because of wars and the intransigence of fundamentalist groups, especially religious ones.

Child with Smallpox

Vaccines are based on the exposure of a small amount of a pathogenic microbe or its components to teach our immune system to recognize it and to be prepared (active immunization) for an upcoming encounter. Thanks to the memory of this contact with the vaccine (immunological memory), our defences are prepared against future infectious aggressions. If a significant number of the population is vaccinated, in addition to the fact that the vaccinated persons are protected, indirect protection is conferred on the weaker persons who have not been able to be vaccinated (herd or group immunity). It should be noted that not all people respond equally to vaccines. Vaccine protection is usually lower in the elderly, whose defences are gradually weakening, and in new-borns whose immune system needs to mature. For these groups of people and for those who can not be vaccinated for medical reasons, it is essential that we all be vaccinated.

Some vaccines, such as Sabin polio or triple virus vaccines against measles, mumps, and rubella, are made up of viruses and other live attenuated (weakened) germs. These vaccines cause a mild infection, but confer a long-lasting acquired immunity but cannot be used in pregnant women, the elderly, or those who are debilitated because they could cause a serious infection. Other vaccines are made up of killed or inactivated whole viruses or microbes, such as polio Salk, rabies vaccine, or some flu vaccines. Toxoids are composed of microbial toxins, such as tetanus or diphtheria that have lost their toxicity. Others have subunits or fragments of the microorganism (antigens) capable of stimulating defences. Recombinant vaccines, against hepatitis B, are obtained by genetic engineering. These vaccines are safer but their effect is weaker and several doses are necessary for a good immunization. Conjugate vaccines against meningitis or pneumonias are being developed that include adjuvants to enhance their immune stimulatory action and nucleic acid vaccines that allow the production of immunizing proteins when injected into muscle or skin. Knowledge of the genome of an increasing number of microbes is enabling the creation of vaccines by reverse vaccinology. These vaccines would be based on the properties of proteins that can be predicted from known gene sequences. Vaccines against meningitis, cavities, malaria, AIDS or herpes are being designed. For these diseases the aim is twofold, both protective and therapeutic.

Imagen realizada por Tania Quindós González

The ideal vaccine would be one that could be ingested (edible), applied to the skin (patch) or inhaled (aerosols) rather than injected. These painless vaccines would replace the more than twenty injections a person can receive during his or her lifetime. The fear of injections would be avoided and the immune defences of the cutaneous, respiratory and digestive mucous membranes would be stimulated, as well as the systemic defences against these diseases. There are promising studies with plants and fruits (rice, wheat, banana, etc.) that through genetic engineering can produce large quantities of antigens. Their thick walls resist the degrading effect of gastric acids and bile salts during their passage through the digestive system, allowing the release of immunostimulatory antigens in the intestine. These edible vaccines would be very effective in combating diarrhoeal diseases that cause high infant mortality. Other ideal properties of vaccines are that they immunize with a single dose, that they are stable without refrigeration (no cold chain), inexpensive and available to all. However, we still do not have effective vaccines against the three infections that cause the most illness and death in our world, malaria, tuberculosis and AIDS, although vaccines against more than one hundred diseases are in experimental study. Future challenges include the design of personalized vaccines, the development of vaccines against non-communicable diseases: cancer (colon, breast or prostate), drug addictions (cocaine) or against some neurodegenerative diseases (Alzheimer’s).

The vaccines are still not perfect and all have some unpleasant effect, either because they cause a little discomfort if injected or a slight general malaise sometimes accompanied by fever. Some side effects can be serious, even in the worst cases, there can be one death per million vaccinated. Many parents in economically rich countries are unaware of the millions of deaths prevented by vaccines and the suffering of children suffering from pertussis, diphtheria, polio or measles. We tend to consider that the risk of these diseases is low and neglect or idleness in the routine vaccination of children is a serious threat. More children and adults are suffering from vaccine-preventable diseases such as measles, diphtheria or polio, which can cause serious sequelae and even death. Despite the fallacies on which the anti-vaccine movements are based and the media echo that accompanies them, it has been amply demonstrated that all vaccines bring far more benefits than harms and are infinitely safer for people who are vaccinated than suffering from the diseases they protect against. No vaccine is related to autism or other diseases with which some unscrupulous people have wanted to associate them, as demonstrated by multiple studies of great magnitude, seriousness and scientific rigor. As it is attributed to Hippocrates of Cos ‘Science and opinion are important: the first generates knowledge, the second ignorance’. Anti-vax movements are based on opinions, beliefs and misunderstandings, but not on scientific facts and the damage they cause is immense and unpredictable. I believe that it is an important duty of all scientists to encourage vaccination and to underline the importance and benefits that vaccination brings to our society.

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