Vaccine

The name "vaccine and vaccination" is derived from vacca (Latin for cow). Liquids containing cowpox viruses were used to effectively vaccinate against smallpox in England from 1796 following the pioneering steps taken by Edward Jenner.

A vaccine is a biological agent that serves to stimulate the immune system so that it develops a positive vaccination response against the antigenic components contained in the agent. Vaccines and the associated immunoprophylaxis play a decisive role in individual and collective protection, especially in the case of viral infections for which there is still no major antidote (see SARS-Cov-2). Not only individuals benefit from the vaccination (individual protection), but also a larger collective (collective protection) if the vaccination coverage rate is high enough.

The aim of a vaccination campaign during an epidemic or pandemic is to achieve herd immunity. Herd immunity makes it possible to prevent the epidemic spread of a pathogen. For example, in 1977 in the village of Merka in Somalia, the cook Ali Maow Maalin was the last person to contract smallpox. Today, infectious smallpox no longer exists in nature, as the infection is only passed on from person to person. However, lyophilized smallpox viruses are still stored in 2 laboratories around the world.

A distinction is made between the following immunization principles:

Passive immunization: Injection of differently prepared gamma globulin fractions from donors. Examples of the use of passive immunization are:

• Tetanus (human hyperimmunoglobulin is present)
• Rabies (human hyperimmunoglobulin is available)
• Cytomegalovirus infection
• Botulism (polyvalent gamma globulin from horse)
• Clostridium difficile (recurrences)
• Diphtheria
• Hepatitis A (human hyperimmunoglobulin is present)
• Hepatitis B (human hyperimmunoglobulin is present)
• Measles (a human hyperimmunoglobulin is not available, but as most people have measles antibodies in their blood, a normal gamma globulin is sufficient)
• Varicella zoster virus (human hyperimmunoglobulin)
• RSV infection (genetically engineered)
• Rubella

Active immunization : application of the antigen to stimulate the body's own immune system). The following options for active immunization are available:

Inactivated vaccines contain either inactivated whole pathogens (particulate vaccines) or only important antigenic components (proteins or polysaccharides) that have been extracted from natural pathogens or produced recombinantly (using genetic engineering). For example, the particles of influenza viruses are split (split vaccines) to extract the antigenic substances in the envelope (e.g. neuraminidase). In order to obtain a satisfactory immune response to the dead antigens, an additional administration of adjuvants is often necessary (e.g. aluminum hydroxide -ALOH ). They promote a pro-inflammatory immune response by mediating so-called "danger signals" and activating the inflammasome, among other things. These vaccines are also known as adsorbate vaccines.

• Subunit and split vaccines (do not contain completely killed pathogens, but only biomolecules obtained from them or genetically engineered. Most flu vaccines are split vaccines)
• Conjugate vacc ines (are sub-unit vaccines in which the pathogen molecules are not introduced directly into the vaccine, but are previously bound to proteins (conjugates), which represent a carrier substance).

• VLP vaccines (VLP is the acronym for "virus-like particles"; these are virus particles that do not contain nucleic acids. This means that the particles cannot multiply in the target cells. They are also not capable of delivering a transgene)

• Toxoid vacc ines (special form of inactivated vaccines): Toxoid vaccines (formalin-inactivated toxin = toxoid); the antibodies are not directed against the pathogen itself but against the toxin of the pathogen.

Live vaccines either contain attenuated pathogens that are weakened in their virulence but are still capable of reproducing, or they are based on vectorized viruses as carriers of the genetic pathogen information.

• Attenuated pathogens: These are still capable of replication, but only induce an attenuated clinical picture. Their genetic changes, which have resulted in the loss of their virulence, are either caused by spotaneous mutation or by multiple passages of the cultures. The advantage of live vaccines is that they mimic a natural infection, which can be humoral or cell-mediated. The disadvantage is the latency period until the body's own immune system has produced sufficient antibodies to guarantee vaccination protection.
• Vector vaccines: here the viral genetic material is incorporated into harmless carrier viruses (e.g. the modified vaccinia Ankara virus) and injected as a vaccine. Although these carrier viruses can penetrate human cells and possibly multiply there, they do not lead to an outbreak of disease. The infected cell then produces the pathogen protein on the basis of the transgenic gene for a period of time, while the organimus produces the desired protective antibody.

Gene-based vaccines: In these vaccines, the organimsus produces the antigen itself like a copying machine. The approach of gene-based vaccines is considered promising, as they can be produced relatively quickly and in large quantities and - should the pathogen mutate - can be modified.

• RNA vaccines: these, such as BNT162/BioNTech/Fosun/Pfizer and mRNA-1273/Moderna/NIAID, usually consist of single-stranded messenger ribonucleic acid (mRNA). This contains the genetic information for building a protein. In the cytosol, the mRNA is bound by ribosomes and a peptide is catalyzed. The RNA in the vaccines is usually packaged in liposomes or lipid nanoparticles (LNP). As the antigen is produced in the cells of the organism and in large quantities, the immune reaction is generally strong.
• DNA vaccines: these consist of a piece of viral DNA inserted into a bacterial plasmid. This is taken up into the target cell, generates an mRNA that is read by ribosomes in the cytosol of the cell and converted into the viral antigen (Ghaffarifar F 2018). A DNA vaccine under development for the coronavirus vaccine is INO-4800 - Inovio Pharmaceuticals).

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Examples of diseases for which inactivated vaccines (T) are available:

• Cholera (T)
• TBE = tick-borne encephalitis (T)
• Genital warts caused by human papillomavirus (HPV) (T))
• Haemophilus influenzae b infection (Hib infection) (T)
• Hepatitis A (T)
• Hepatitis B (T)
• Herpes zoster (shingles) (L, T)
• Meningitis or sepsis caused by meningococci of serogroups A, B, C, W135 and Y (T)
• Influenza (seasonal true flu) (L, T)
• Genital / anal cancers caused by human papillomaviruses (HPV) (T)
• Japanese encephalitis (T)
• Pneumonia and otitis media caused by pneumococci (T)
• Pertussis (whooping cough) (T)
• Polio (T)
• Tetanus = tetanus (T)
• Rabies (T)
• Typhoid (L, T)
• Human papillomavirus (HPV) (T)

Examples of diseases for which live vaccines (L) are available:

• Cholera (L)
• Yellow fever (L)
• Herpes zoster (shingles) (L, T)
• Influenza (seasonal true flu) (L, T)
• Measles (L)
• Mumps (L)
• Smallpox (L)
• Poliomyelitis (L)
• Rotavirus (vomiting diarrhea) (L)
• Rubella (L)
• Salmonella (L)
• Tuberculosis (L)
• Typhoid fever (L, T)
• Varicella (chickenpox) (L)

Vector vaccines:

• Diphtheria (V)
• Ebola (V)
• Corona viruses (SARS/MERS)
• Flaviviruses (e.g. Zika virus)
• Dengue virus

Gene-based vaccines: In these vaccines, the organimsus produces the antigen itself like a copying machine. The approach of gene-based vaccines is considered promising, as they can be produced relatively quickly and in large quantities and - should the pathogen mutate - can be modified.

RNA vaccines: mRNA is packaged in lipid nanoparticles and enters the cell nucleus. The translation of the mRNA leads to the formation of the viral allergen, against which the immune system forms protective antibodies. Examples of RNA vaccines are:

• BNT162/BioNTech/Fosun/Pfizer(SARS-CoV-2)
• and
• mRNA-1273/Moderna/NIAID (SARS-CoV-2)

DNA vaccines

• INO-4800 - Inovio Pharmaceuticals (INO-4800 is a DNA vaccine candidate designed to target the SARS-CoV-2 coronavirus. The nucleic acid-based vaccine is stable at room temperature for more than one year and does not need to be transported or stored frozen. The INO-4800 vaccine contains the plasmid pGX9501, which encodes the full-length spike glycoprotein of SARS-CoV-2. During application, a short electrical pulse is used to reversibly open small pores in the cell so that the plasmids can penetrate).

Vaccines and the associated immune prophylaxis play a decisive role in individual and collective protection, especially in the case of viral infections for which no major antidote is yet available (see COVID-19). Not only individuals benefit from vaccination (individual protection), but also a larger collective (collective protection) if the vaccination coverage rate is high enough. The aim of a vaccination campaign in the case of an epidemic or pandemic is to achieve herd immunity, which is ultimately capable of preventing the epidemic spread of a pathogen. For example, in the village of Merka in Somalia, Ali Maow Maalin was the last person to contract smallpox. Today, infectious smallpox no longer exists in nature, as the infection is only passed from person to person. However, lyophilized smallpox viruses are still stored in 2 laboratories in the world.

Serious so-called adverse drug reactions (ADRs) after vaccinations are very rare. According to § 6 para. 1 Infektionsschutzgesetz (IfSG), the suspicion of a health damage exceeding the usual extent of a vaccination reaction has to be reported by name. The notification is made by the physician to the public health department. According to § 11 para. 4 IfSG, the health offices are obliged to report the reported suspected cases to the competent Land authority and the competent higher federal authority, the Paul Ehrlich Institute, in accordance with the provisions of data protection in pseudonymised form (personal details are to be made unidentifiable). The obligation to report according to IfSG applies in any case (Robert Koch Institute 2020).

Recently, tumor vaccines have also been propagated, in which no microbial antigens but tunor antigens are applied.

1. Agnandji S T et al. (2016) Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. The New England journal of medicine 374: 1647-1660.
2. Afrough B et al. (2019) Emerging viruses and current strategies for vaccine intervention. Clin Exp Immunol 196: 157-166.
3. Ghaffarifar F (2018) Plasmid DNA vaccines: where are we now? Drugs Today (Barc) 54: 315-333.
4. Hirao LA et al (2008) Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques. Vaccine 26:3112-3120.
5. Hof H (2019) Vaccination. In: Hof H, Schlüter D, Dörries R, eds Duale Reihe Medizinische Mikrobiologie. 7th, completely revised and expanded edition. Stuttgart: Thieme pp.736-748.
6. Li L et al (2016) Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines 15:313-329.
7. Communication of the Robert Koch Institute (retrieved on 25/1/2020).