Vaccinations

The name "vaccination " is derived from vacca (Latin for cow). After the pioneering steps of Edward Jenner, fluids containing cowpox viruses were used to effectively vaccinate against smallpox in England from 1796.

According to the IfSG, vaccination is the administration of a vaccine with the aim of protecting against a transmissible disease.

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 SARS-Cov-2). 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 during an epidemic or pandemic is to achieve herd immunity. Herd immunity prevents 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 from person to person. However, lyophilized smallpox viruses are still stored in 2 laboratories around the world.

A distinction is made between the following vaccination 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 (equine polyvalent gamma globulin present)
• Clostridium difficile (recurrences)
• Diphtheria
• Hepatitis A (human hyperimmunoglobulin present)
• Hepatitis B (human hyperimmunoglobulin is present)
• Measles (human hyperimmunoglobulin is not available, but since most people have measles antibodies in their blood, normal gamma globulin is sufficient)
• Varicella-zoster virus (human hyperimmunoglobulin)
• RSV infection (genetically engineered)
• Rubella

Active immun ization: application of the antigen to stimulate the body's own immune system). The following possibilities of active immunization are given:

Inactivated vaccines contain either inactivated whole pathogens (particulate vaccines) or only important antigenic components (proteins or polysaccharides) extracted from antigenic pathogens, or recombinant (produced by genetic engineering). For example, the particles of influenza viruses are split (split vaccines) to extract the antigenic substances in the envelope (e.g. neuraminidase). To obtain a satisfactory immune response to the dead antigens, additional administration of adjuvants is often required (e.g., aluminum hydroxide). These vaccines are also referred to as adsorbate vaccines.

• Subunit and split vaccines (do not contain complete killed pathogens, but only biomolecules derived or genetically engineered from them. Most influenza vaccines are split vaccines).
• Conjugate vaccines (are subunit vaccines in which the pathogen molecules are not introduced directly into the vaccine, but are bound beforehand to proteins (conjugates) that constitute a carrier substance).

• VLP vaccines (VLP is the acronym for "virus-like particles; these are virus particles, but they do not contain nucleic acids. Thus, the particles cannot replicate in the target cells. They are also not capable of delivering a transgene).

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

Live vaccines contain either attenuated pathogens that have been 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 induce only an attenuated clinical picture. Their genetic alterations, which have resulted in the loss of their virulence, are either due to spot mutation or to multiple passages of the cultures. The advantage of live vaccines is that they mimic an anti-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 ensure vaccine protection.
• Vector vaccines: here the viral genetic material is incorporated into harmless carrier viruses (e.g. in the Modified-Vaccinia-Ankara-Virus) and injected as a vaccine. These carrier viruses can penetrate human cells and possibly also multiply there, but do not lead to the outbreak of disease. The infected cell then produces the pathogen protein for a time on the basis of the transgenic gene, and the organism produces the desired protective antibody.

Gene-based vaccines: In these vaccines, the organism itself produces the antigen like a copying machine. The approach of gene-based vaccines is considered promising because they can be produced relatively quickly and in large quantities and, should the pathogen mutate, they 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 the assembly of a protein. In the cytosol, the mRNA is bound by ribosomes and catalyzes a peptide. The RNA in vaccines is usually packaged in liposomes or lipid nanoparticles (LNP). Since the antigen is produced in the cells of the organism and in large quantities, the immune response is generally strong.
• DNA vaccines: these consist of a viral DNA fragment inserted into a bacterial plasmid. This is taken up into the target cell, generates an mRNA which is transcribed by ribosomes bound in the cytosol of the cell and converted into the viral antigen (Ghaffarifar F 2018). A DNA vaccine under development in Corona is INO-4800 - Inovio Pharmaceuticals).

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

• Cholera (T)
• TBE = early summer meningoencephalitis (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)
• Cancers of the genital / anal area caused by human papillomavirus (HPV) (T)
• Japanese encephalitis (T)
• Pneumococcal pneumonia and otitis media (T)
• Pertussis (whooping cough) (T)
• Polio (T)
• Tetanus = tetanus (T)
• Rabies (T)
• Typhoid fever (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 gene-based vaccines approach is considered promising because they can be produced relatively quickly and in large quantities and, should the pathogen mutate, can be modified.

RNA vaccines: mRNA is packaged into lipid nanoparticles and enters the nucleus. Translation of the mRNA leads to the formation of the viral allergen, against which the immune system forms protective antibodies. Examples of RNA vaccines include:

• 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 targeted to the SARS-CoV-2 coronavirus. The nucleic acid-based vaccine is stable for more than one year at room temperature and does not require frozen transport or storage. The INO-4800 vaccine contains plasmid pGX9501, which encodes the full-length spike glycoprotein of SARS-CoV-2. During application, a brief electrical pulse is used to reversibly open small pores in the cell to allow plasmid entry).

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).