Vaccines

Definition, Type of Immunity and Types of Vaccines, Ingredients

All the information in this article has been slightly readapted and rearranged from original sources for treating a subject so actual and sensitive. The purpose is to assemble these data in one place to provide additional details to whom interested considered the broad data available at this time and the need for many of us to understand always better and more around this matter.

A vaccine is a substance that is introduced into the body to stimulate the immune response and to prevent infectious diseases.

Vaccines are made from dead or inactive microbes so that they are unable to cause disease. The antigen in the vaccine stimulates the production of antibodies which are the same as those produced if the person was exposed to the pathogen. If the vaccinated person comes in contact with the agent responsible for the disease, the immune system remembers the antibodies produced to the vaccine and can react faster becoming this way immune to the pathogen.

Vaccines are usually given by an injection and when a high number of people have been vaccinated or been exposed to the same pathogen, herd immunity is reached. Herd immunity is the resistance of a group of people to an infection and is due to the immunity of a high proportion of the population to the disease. If this proportion is high enough then the small number of people who have no immunity will be protected because there are not enough susceptible people to allow transmission of the pathogen.

Vaccination is a form of artificial immunity and the process and steps of preparation, evaluation, safety controls and approval are extremely long. By artificially stimulating the adaptive immune defenses, a vaccine triggers memory cell production like that would happen during a primary response, in this way the patient is capable to build a strong secondary response after exposure to the pathogen.

Natural active immunity is adaptive immunity that develops after natural exposure to a pathogen, as the lifelong immunity that develops after recovery from a chickenpox or measles infection. The length of time that an individual is protected can vary significantly based on the pathogen and antigens involved.

For example, activation of adaptive immunity by protein spike structures during an intracellular viral infection can activate lifelong immunity, while activation by carbohydrate capsule antigens during an extracellular bacterial infection may activate shorter-term immunity.

Natural passive immunity involves the natural passage of antibodies from a mother to her child before and after birth. IgG is the only antibody class that can cross the placenta from the mother’s blood to the fetal blood supply. Placental transfer of IgG is an important passive immune defense for the infant that lasts up to six months after birth. Secretory IgA can also be transferred from mother to infant through breast milk.

Artificial passive immunity refers to the transfer of antibodies produced by a donor to another individual. This transfer of antibodies may be done as a prophylactic measure to prevent disease after exposure to a pathogen, or as a strategy for treating an active infection. For example, artificial passive immunity is commonly used for post-exposure prophylaxis against rabies, hepatitis A, hepatitis B, and chickenpox in high-risk individuals. Artificial passive immunity is also used for the treatment of diseases caused by bacterial toxins, including tetanus, botulism, and diphtheria.

Active infections treated by artificial passive immunity made by convalescent serum from recovered patients has been also used to treat Covid-19 patients so as for infections in immunocompromised patients and Ebola virus infections.

Artificial active immunity is the foundation for vaccination. It involves the activation of adaptive immunity through the measured exposure of an individual to weakened or inactivated pathogens, or preparations consisting of key pathogen antigens.

The developer of the vaccination process was actually the English physician Edward Jenner (1749–1823) who observed that cows who developed cowpox, a disease similar to smallpox but milder, were immune to the more serious smallpox. This led Jenner to hypothesize that exposure to a less virulent pathogen could provide immune protection against a more virulent pathogen.

In 1796, Jenner tested his hypothesis by obtaining infectious samples from a cow’s active cowpox lesion and injecting the materials into a young boy. The boy developed a mild infection that included a low-grade fever, discomfort in his armpit and loss of appetite. When the boy was later infected with infectious samples from smallpox lesions, he did not contract smallpox. 

This new approach was termed vaccination, a name deriving from the use of cowpox (from Latin vacca which means cow) to protect against smallpox. Today, it is known that Jenner’s vaccine worked because the cowpox virus is genetically and antigenically related to the Variola viruses that caused smallpox.

The success of Jenner’s smallpox vaccination drove other scientists to develop vaccines for other diseases. The most famous was Louis Pasteur, who developed vaccines for rabiescholera, and anthrax. During the twentieth and twenty-first centuries, effective vaccines were developed to prevent a wide range of diseases caused by viruses (chickenpox and shingles, hepatitis, measles, mumps, polio, and yellow fever) and bacteria (diphtheria, pneumococcal pneumonia, tetanus, and whooping cough).

For a vaccine to provide protection against a disease, it must expose an individual to pathogen-specific antigens that will stimulate a protective adaptive immune response, this, of course involves some risks as the development of adverse reactions.

Various types of vaccines have been developed for minimizing the risk of collateral effects.

Live attenuated vaccines expose an individual to a weakened strain of a pathogen with the objective of establishing a subclinical infection that will activate the adaptive immune defenses. Pathogens are attenuated to decrease their virulence using methods like genetic manipulation, to eliminate key virulence factors, or long-term culturing in an unnatural host or environment, to promote mutations and decrease virulence.

Live attenuated vaccines activate both cellular and humoral immunity and stimulate the development of memory for long-lasting immunity. Disadvantages associated with live attenuated vaccines include the challenges of long-term storage and transport in addition to the potential for a patient to develop signs and symptoms of disease during the active infection, especially immunocompromised patients. There is also a risk for the attenuated pathogen to revert back to full virulence.

Examples of this type of vaccines are chickenpox, measles, mumps, tuberculosis, typhoid fever, yellow fever.

Inactivated vaccines contain whole pathogens that have been killed or inactivated with heat, chemicals, or radiation. The inactivation process must not affect the structure of key antigens on the pathogen for these types of vaccines to be effective.

Inactivated vaccines do not produce an active infection because the pathogen is killed or inactivated, and the resulting immune response is weaker than that provoked by a live attenuated vaccine. Typically, the response involves only humoral immunity, and which means antibodies production, besides the pathogen cannot be transmitted to other individuals. In addition, inactivated vaccines usually require higher doses and multiple boosters, possibly causing inflammatory reactions at the site of injection.

Despite these disadvantages, inactivated vaccines do have the advantages of long-term storage stability and facility of transport. Also, there is no risk of causing severe active infections. Inactivated vaccines can also provoke side effects.

Examples of inactivated vaccines are cholera, hepatitis A, influenza, plague, rabies.

While live attenuated and inactive vaccines expose an individual to a weakened or dead pathogen, subunit vaccines only expose the patient to the key antigens of a pathogen not whole cells or viruses. Subunit vaccines can be produced either by chemically degrading a pathogen and isolating its key antigens or by producing the antigens through genetic engineering. Because these vaccines contain only the essential antigens of a pathogen, the risk of side effects is relatively low.

Examples of this type of vaccines are anthrax, hepatitis B, influenza, meningitis, papillomavirus, pneumococcal pneumonia, whooping cough.

Toxoid vaccines, as subunit vaccines, do not utilize whole pathogen but contain inactivated bacterial toxins, called toxoids. Toxoid vaccines are used to prevent diseases in which bacterial toxins play an important role in pathogenesis. These vaccines activate humoral immunity that neutralizes the toxins.

 Examples are botulism, diphtheria, pertussis, tetanus.

conjugate vaccine is a type of subunit vaccine that consists of a protein conjugated to a capsule polysaccharide. Conjugate vaccines have been developed to enhance the efficacy of subunit vaccines against pathogens that have protective polysaccharide capsules that help them evade phagocytosis, causing invasive infections that can lead to meningitis and other serious conditions.

The subunit vaccines against these pathogens introduce T-independent capsular polysaccharide antigens that result in the production of antibodies that can neutralize the capsule and so fight the infection; however, children under the age of two years do not respond effectively to these vaccines.

Examples of conjugate vaccines are haemophilus influenzaeStreptococcus pneumoniaeNeisseria meningitides.

DNA vaccines represent a relatively new and promising approach to vaccination. A DNA vaccine is produced by incorporating genes for antigens into a recombinant plasmid vaccine. Introduction of the DNA vaccine into a patient leads to uptake of the recombinant plasmid by some of the patient’s cells, followed by transcription and translation of antigens and presentation of these antigens to the MHC I, the immunocomplex of histocompatibility I to activate adaptive immunity.

This results in the stimulation of both humoral and cellular immunity without the risk of active disease associated with live attenuated vaccines.

DNA vaccines for various cancers and viral pathogens such as HIV, HPV, and hepatitis B and C are currently in development.

Some DNA vaccines are already in use. In 2005, a DNA vaccine against West Nile virus was approved for use in horses in the United States. Canada has also approved a DNA vaccine to protect fish from infectious hematopoietic necrosis virus. A DNA vaccine against Japanese encephalitis virus was approved for use in humans in 2010 in Australia.

DNA plasmid vaccines consist of a small circular piece of DNA called a plasmid that carries genes encoding proteins from the pathogen of interest. NIAID’s Vaccine Research Center has developed DNA vaccines to address several viral disease threats during outbreaks, including SARS coronavirus (SARS-CoV) in 2003, H5N1 avian influenza in 2005, H1N1 pandemic influenza in 2009, and Zika virus in 2016.

Vaccines based on messenger RNA (mRNA), an intermediary between DNA and protein, also are being developed. Recent technological advances have largely overcome issues with the instability of mRNA and the difficulty of delivering it into cells, and some mRNA vaccines have demonstrated encouraging early results.

Of course, these articles were written sometime before of current situation with SARS-CoV-2 and related types of vaccines since the majority of vaccines for Covid-19 are constitute from mRNA.

Vaccine Ingredients

Vaccines Ingredients are usually preservatives, adjuvants, stabilizers, cells cultures materials, residual antibiotics.

Thimerosal is a preservative which contains mercury used only in multi-dose vials of flu vaccine to prevent contamination.

Adjuvants are compounds like aluminum salts used to help boost the body’s response to the vaccine.

For stabilizers are used sugars or gelatin to keep the vaccine effective after manufacture.

As residual cell culture materials are used egg proteins to grow enough of the virus or bacteria to make the vaccine.

Residual inactivating ingredients as formaldehyde are needed to kill viruses or inactivate toxins during the manufacturing process.

CDC states that antibiotics like penicillin responsible of allergic reactions are not used in vaccines and that thimerosal has a different form of mercury, (ethylmercury), than the kind that causes mercury poisoning (methylmercury). “It’s safe to use ethylmercury in vaccines because it’s processed differently in the body and it’s less likely to build up in the body — and because it’s used in tiny amounts”. Most vaccines, they specify, do not have any thimerosal in them.

Because influenza and yellow fever vaccines are both made in eggs, egg proteins are present in the final products. But today there are two new flu vaccines available for people with egg allergies. They suggest that people who have severe egg allergies should be vaccinated in a medical setting and be supervised by a health care professional who can recognize and manage severe allergic conditions.

They also report that formaldehyde is diluted during the vaccine manufacturing process, but residual quantities of formaldehyde may be found in some current vaccines, and that the amount of formaldehyde present in some vaccines is so small compared to the concentration that occurs naturally in the body that it does not pose a safety concern.

Thanks for Reading.

Mariarosaria M.

Sources:

https://microbiologysociety.org/why-microbiology-matters/what-is-microbiology/microbes-and-the-human-body/vaccination.html

https://www.cdc.gov/vaccines/parents/ingredients.html

https://www.niaid.nih.gov/research/vaccine-types

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