A vaccine , also called the vaccine or the vaccine ( lat. Vaccinus “from cows”; see vaccination ), is a biologically or genetically engineered antigen , usually consisting of protein or genetic material fragments or killed or weakened pathogens . A vaccine can consist of an antigen from a single pathogen as well as a mixture of several antigens from different pathogens or pathogen strains and possibly other additives. As part of a vaccination, the vaccine is used to specifically activate the immune system with regard to a specific pathogen or group of pathogens.
For this purpose, the reaction of the immune system is used to provoke an immune response in the presence of pathogens or their specific parts (e.g. surface proteins as antigens ) . This leads to the formation of antibodies and specialized T helper cells , which then offer long-lasting protection against the respective disease , which, depending on the pathogen, can last between a few years and a lifetime.
That smallpox was the first disease in which an attempt was made individuals through deliberate infection for other pathogens immunize ( Variolation ). It is believed that these attempts were made in either India or China as early as 1000 BC. Began. Chinese doctors selected people with mild disease to obtain the vaccine and removed pieces of smallpox crust from those infected. The pieces were ground to a powder and inserted into the nose of the person to be vaccinated.
Lady Mary Wortley Montagu reported in 1718 that the Turks in the Ottoman Empire similarly exposed themselves to the body fluids of easily infected people, and used this method on her own children. In the years from 1770 at the latest, six people, including Sevel, Jensen, Jesty (1774), Rendall and Plett (1791), observed that milkers had become immune to human pox after they had survived the comparatively harmless cowpox . They then successfully vaccinated their family and friends with cowpox lymph .
The English country doctor Edward Jenner learned from doctors with whom he was in contact that people apparently did not respond to smallpox variolation if they had previously had cowpox. Jenner therefore hypothesized that inoculation with cowpox enables the same immunity as a survived illness from cowpox and therefore offers protection against smallpox. Jenner took infectious fluids from the hand of cowpox-infected maid Sarah Nelmes and introduced them by injection or scratching into the arm of eight-year-old healthy James Phipps . James developed symptoms of cowpox infection from which he made a full recovery. 48 days later, Jenner performed a smallpox variolation that was established at that time. The boy did not develop symptoms of smallpox.
Live attenuated vaccine
Such live vaccines contain weakened ( attenuated ) viruses or bacteria , which can usually still multiply (but not with the MVA virus) and trigger an immune response, but usually no disease. A live attenuated vaccine is usually much more effective than a dead vaccine. In rare cases, after the use of such a vaccine, when the pathogen may multiply, a mutation ( reversion ) in the direction of the non-weakened initial form can occur, which can then lead to the disease. Examples of attenuated vaccines are the oral polio vaccination (OPV), which was abandoned in Europe and which very rarely caused vaccination poliomyelitis , the MMR (V) vaccine , the smallpox vaccine of that time , the Bacillus Calmette-Guérin and vaccines against yellow fever . For typhoid vaccination both Lebend- stand and inactivated vaccines are available. Attenuation usually takes place through serial infections of alien cell cultures , embryonated chicken eggs or test animals , in which the respective pathogen adapts to the new host species and often at the same time loses adaptations to the type of vaccinated person, which is expressed in a reduction in pathogenicity .
Some live vaccines are treated by other methods. Cold-adapted strains can only multiply at temperatures around 25 ° C , which limits the virus to the upper respiratory tract. In the case of temperature-sensitive strains , replication is limited to a temperature range of 38–39 ° C and the lower respiratory tract is not affected.
Inactivated vaccines contain inactivated or killed viruses or bacteria or components of viruses, bacteria or toxins . These can no longer multiply in the body or poison it, as tetanospasmin could, but they also trigger a defense reaction (immune reaction). Examples are the toxoid vaccines and vaccines against influenza ( influenza vaccine ), cholera , bubonic plague , hepatitis A or hepatitis B ( hepatitis B vaccine ).
Inactivated vaccines are divided into:
- Toxoids : Toxoids are detoxified toxins from pathogenic microorganisms. These vaccines are used in cases in which it is not the pathogens themselves but, as in tetanus and diphtheria , mainly their toxins that cause the symptoms of the disease.
- Inactivated whole-particle vaccines : Inactivation of the viruses by fixation using a combined application of formaldehyde , beta-propiolactone and psoralen
- Split vaccines : Destruction of the virus surface with detergents or strong organic solvents.
- Subunit vaccines : the surface is completely dissolved and specific components ( hemagglutinin and neuraminidase proteins) are cleaned out . Another possibility is toproducethe subunits recombinantly . Subunit vaccines are only slightly immunogenic , but have few side effects.
Inactivated vaccines require immunostimulating adjuvants , mostly aluminum adjuvants.
Advantages and disadvantages of live and dead vaccines
Live vaccines are usually a little easier to obtain than dead vaccines, both trigger long-lasting to lifelong humoral immune responses , while live vaccines also trigger a cellular immune response . However, live vaccines are somewhat less well tolerated and carry the - very low - risk of a reverse mutation into pathogens and thus triggering a (mostly weakened) form of the disease against which they were originally intended to protect.
Therefore, according to the current recommendations of the Robert Koch Institute responsible for this in Germany, pregnancy should be avoided for at least one month after vaccination with live vaccines. On the other hand, due vaccinations with dead vaccines can be given to expectant mothers in the second and third trimester of pregnancy without hesitation; In the first third , on the other hand , to rule out any risk to the child, only those dead substance vaccinations that are urgently indicated on an individual basis should be carried out . During the subsequent breastfeeding period , vaccinations (with the exception of yellow fever ) are generally possible without restrictions. In the case of live vaccination with the rotavirus vaccine , one hour after and before the vaccination should not be breast-fed in order to optimize the effect.
Different live vaccines can easily be administered at the same time. If vaccination is not carried out at the same time, the interval between two live vaccinations should be at least four weeks. This does not apply to dead vaccines or a combination with them.
Other types of vaccines
A number of other, sometimes experimental, techniques are used in vaccine design:
- Conjugated vaccines : some bacteria have polysaccharide outer shells that provoke only weak immune responses. By associating these outer shells with proteins (like toxins ), the immune system can be made to recognize the polysaccharides like protein antigens.
- Instead of completely attenuated or inactive pathogens, an immune response can also be provoked by fragments (i.e. parts).
- Recombinant vectors : By combining the physiology of one microorganism with the DNA of another, immunity against pathogens with complex infection processes can be created.
- DNA vaccination : In recent years, an experimental form of vaccination has emerged that is based on the DNA of the agent and is applied by injection, inoculation patches or gene guns . Here, viral or bacterial DNA is introduced into the host organism and expressed on site . This causes both a humoral and a cellular immune response. According to the current state of research, there are no side effects of the usual vaccination methods. Theoretical risks, however, are the integration of the foreign DNA into the genome and the possibility of an antibody response to the DNA molecule itself.
- RNA vaccine : Similar to DNA vaccination, genetic code is used, but in the form of stabilized mRNA of the respective antigen. There are no self-replicating and self-amplifying mRNA vaccines (RNA replicon ). The advantages of the method are the better safety profile compared to DNA, since permanent integration into the genome is excluded and specific antibody responses to RNA molecules do not occur. Another advantage of the stabilized mRNA is that it can be precisely metered. If necessary, mRNA vaccines can be administered intranasally, so they do not have to be injected. Various methods for intensifying the immune response have already been tried, for example complexation with protamine . The main areas of application so far have been cancer therapy and infection prophylaxis.
- With effector memory T-cell vaccines (not to be confused with T-cell vaccination ), a cellular immune response is induced. The aim of these vaccines, which are mostly based on short peptides, is the generation of cytotoxic T cells , a small part (less than 5%) of which remain in the organism as memory T cells after the vaccination . The preferred locations for the memory cells are the bone marrow and non-lymphatic and lymphatic tissue. Even decades after vaccination, effector T memory cells can trigger an immune response within a few hours of renewed contact with the same antigen and thus develop an adequate protective effect. The protective effect of the memory cells can last for many years. Corresponding vaccines, for example against the HI virus or the human cytomegalovirus , are still being developed.
Vaccines by application
Vaccines against infections with viruses are z. B. Adenovirus Vaccines , Dengue Virus Vaccines , Hepatitis B Vaccines , Hepatitis A Vaccines , TBE Vaccines , Yellow Fever Vaccines , Influenza Vaccines , Japanese Encephalitis Vaccines , Measles Vaccines , the MMR Vaccine , the MMRV Vaccine , Mumps , Smallpox vaccines like Modified Vaccinia Ankara Virus , Polio Vaccines , Rotavirus Vaccines , Rubella Vaccines, and Rabies Vaccines . HPV vaccines are used to prevent diseases, including cancer, caused by human papillomavirus .
Vaccines against infections caused by bacteria include anthrax vaccines , the Bacillus Calmette-Guerin , cholera vaccines , DTP vaccines , Hib vaccines , typhoid vaccines , diphtheria vaccines , typhoid fever vaccines , tetanus vaccines , meningitis vaccines , pertussis vaccines , Pestimpfstoffe and Pneumococcusimpfstoffe .
Vaccines - against different types of pathogens - can also be combined in one finished product. The hexavalent vaccine, for example, prevents diseases caused by certain bacteria ( diphtheria pathogens , tetanus pathogens , whooping cough pathogens ) as well as certain viruses ( poliovirus , HBV , HiB ).
Experimental vaccines against infectious diseases include cytomegalovirus vaccines , Epstein-Barr virus vaccines , hantavirus vaccines , the HIV vaccines like Remune and Ebola vaccines like CAd3-ZEBOV and VSV-EBOV , hepatitis C vaccines , malaria vaccines , and coronavirus vaccines . Vaccines against parasites are under development, e.g. B. Hookworm vaccines , schistosomiasis vaccines , and trypanosomiasis vaccines . Experimental caries vaccines against Streptococcus mutans are being investigated. The vaccines TA-CD and TA-NIC are directed against low molecular weight compounds such as cocaine and nicotine , respectively .
Most vaccines are injected intramuscularly or subcutaneously . For intramuscular injection, a larger muscle is chosen that can better accommodate the volume of the vaccine. For live vaccines, less invasive forms of administration are sometimes also suitable, since they replicate or are replicated in the vaccinated person, e.g. B. Drops for the mucous membranes or aerosol inhalers. Oral vaccination was approved as a polio vaccine. The smallpox vaccine, on the other hand, is scratched into the skin with a bifurcation needle. Experimental forms of application include inoculation patches , gene cannons , electroporation , edible transgenic plants , flying syringes and microneedle arrays.
In the field of livestock vaccination, needle-free, intradermal vaccination using a high-pressure vaccination gun is established.
|Largest vaccine manufacturers (2017)|
Vaccine production is less attractive than conventional drug production given its complexity and higher cost . Manufacturing can take anywhere from months to two years, and the laborious batch test poses a monetary risk. The number of vaccine manufacturers around the world has also declined due to economic considerations. Multiple vaccines are cheaper than the corresponding single vaccines. The share of vaccine costs in the service expenditure of statutory health insurance in Germany is around 0.6%, compared to drug costs around 3.6%.
In view of the threat from pathogens such as bird flu "H5N1" and swine flu "H1N1" , as well as bluetongue and the Schmallenberg virus in the veterinary sector, vaccine production experienced an economic boom worldwide. In 2001, it turned over $ 6.9 billion worldwide. In 2009 it was around $ 25 billion and in 2015 global vaccine manufacturing sales are estimated at $ 56-64 billion.
Other vaccine manufacturers include IDT Biologika . Vaccine manufacturers from emerging countries are z. B. Panacea Biotec , Instituto Butantan , Bio-Manguinhos , Shanghai Pharma , Bharat Biotech , Poonawalla Group (Serum Institute of India), biofarma , Sinovac and Sinopharm .
In terms of the amount of vaccine produced, Europe leads with 76%, followed by North America with 13%.
"Vaccines are drugs within the meaning of Section 2, Paragraph 1, which contain antigens or recombinant nucleic acids and which are intended to be used in humans or animals to generate specific defense and protective substances and, insofar as they contain recombinant nucleic acids, exclusively for Prevention or treatment of infectious diseases are intended. "
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