Vaccine design

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Different vaccines and vaccination vectors

The vaccine design (also vaccine development ) describes procedures for the targeted adaptation of vaccines . Vaccine design is a form of rational design and also uses methods of protein design and vector design to some extent .

properties

A vaccination is intended to provide longer-term protection against illness. In mammals, the adaptive parts of the immune system that develop a form of immunological memory are antibody- producing B cells , T helper cells and cytotoxic T cells . In order to design a vaccine, the antigens to be used in a vaccine must first be identified. An antigen usually has several epitopes to which parts of the adaptive immune response can bind.

As an evolving method, vaccine design consists of the identification of effective epitopes on the basis of previously defined criteria ( scoring ), followed by methods for optimizing the immune response. In contrast to gene therapy with viral vectors , in the case of immunogenic vaccination with viral vectors, it is undesirable for the vector to remain in the vaccinee for a longer period, since this can lead to the development of tolerance. Vaccines can produce immunogenic (e.g. vaccines against pathogens or cancer vaccines ) or tolerogenic effects ( desensitization , e.g. glatiramer acetate ). Development parameters include the identification of the antigens to be used, the form of application , correlates of vaccination protection, animal models , scalability , production capacities , the target profile of the end product, prediction of the epidemiology and the population to be vaccinated.

For attenuated viruses, viral vectors, and DNA vaccines, the vaccine is made by the vaccinee's cells, with native conformation and correct post-translational modifications . Within the cell, the antigens are broken down in the proteasome , the fragments ( peptides ) bind to the antigen peptide transporter , the peptide is imported into the endoplasmic reticulum , the peptide binds to MHCI and the peptide-MHCI complex is exocytosed Cell surface . There the peptide-MHCI complexes are presented to the immune cells and lead to an activation of the cellular immune response.

ID

The epitopes can be characterized by two different strategies. The epitopes can be selected on the basis of empirical knowledge about the immunogenicity or the correlates of vaccination protection against infection on the basis of a previous determination of the immune response against a specific epitope. Alternatively, the epitopes can be selected based on the identification of the epitopes by epitope mapping with the aid of immune sera and memory cells from convalescents .

reviews

Various outcomes can be selected as relevant, e.g. B. Induction of a titer , effectiveness in a neutralization test , ELISA or ELISPOT or by an animal experiment after immunization and subsequent infection (English challenge experiment ) with a record of the pathogenicity index and lethality . In order to reduce the number of test batches, the in vitro methods can be used as a limited preview, but the testing of immunogens is then carried out using a stress test. Occasionally, a hemagglutination inhibition test or various methods to determine the cell viability of antigen- laden sacrificial cells are used after the addition of immune cells .

In addition to the criteria for effectiveness (Engl. Efficacy ) and efficiency (Engl. Efficiency are) of the vaccine candidate and the effectiveness against multiple strains of a pathogen, the immune dominance , the vector type, route of administration , the biological half-life , the storage stability , the cost , extensibility the production capacity in the event of an epidemic , the depot effect , the dose , an immunomodulation , the protective quotient and adverse drug effects are included in an assessment.

Correlates of vaccination protection

vaccine Type Test procedure Protection off
Hepatitis A vaccine Inactivated ELISA 10 mIU / mL
Hepatitis B vaccine HBsAg ELISA 10 mIU / mL
HPV vaccine Virus-like particle ELISA undefined
Influenza vaccine Split or attenuated HAI 1:40 titer
Japanese encephalitis vaccine Inactivated or attenuated Neutralization 1:10 titer
Measles vaccine Attenuated Neutralization 120-200 mIU / mL
Mumps vaccine Attenuated Neutralization? undefined
Polio vaccine Attenuated or inactivated Neutralization 1: 4 to 1: 8 titre
Tetanus vaccine Inactivated Neutralization 0.01 IU / mL
Rabies vaccine Inactivated Neutralization 0.5 IU / mL
Rotavirus vaccine Attenuated Serum IgA undefined
Rubella vaccine Attenuated Immunoprecipitation 10-15 mIU / mL
Smallpox vaccine Attenuated Neutralization 1:20 to 1:32 titer
Varicella vaccine Attenuated FAMA, gpELISA, T cell proliferation 1:64 titer, 5 IU / mL, undefined
TBE vaccination Inactivated Neutralization 125 IU / mL
Yellow fever vaccine Attenuated Neutralization 0.7 LNI

Optimizations

Examples of strategies for strengthening an immune response are revaccinations or dose increases. In order to reduce the effects of immune evasion and a possible vaccine breakthrough (especially in the case of RNA viruses and bacteria ), consensus sequences of an epitope from different strains of a pathogen or mixtures of antigens from different strains (e.g. in the case of the influenza vaccine ) are occasionally used in order to avoid a limited To convey protection against multiple tribes. Using a conserved epitope can extend vaccine protection to multiple strains. Repetitions of epitopes of extracellular antigens can, as thymus-independent antigens, intensify a humoral immune response . The addition of adjuvants can lead to an increase in the immune response. By activating antigen-presenting cells , the vaccine response can be increased. In the case of intracellular pathogens, the immune response can be directed towards cytotoxic T cells . By virus-like particles , and virosomes a sometimes weak immunogenicity of purified antigens (such as subunit vaccines ) are partially compensated. The immune response can be increased by a suitable vector . In the case of DNA vaccines (e.g. by injection or by gene cannon ), RNA vaccines or viral vectors , the antigens are produced intracellularly in the vaccinee; the latter can only be used effectively once per vaccinated person due to vector immunity. In the case of viral vectors, various prime-boost strategies have therefore been developed to enhance the immune response through multiple vaccinations while at the same time circumventing vector immunity, in which different vectors, but with the same antigen, are used for the individual vaccinations.

history

First form of vaccine development

Edward Jenner's earliest vaccines were made from pathogens of other species (e.g., cowpox ) that were sufficiently similar to human pathogens to trigger an immune response in less disease. In addition to the use of pathogens from other species, other methods were subsequently added. Viral next-generation vaccines composed of inactivated (z. B. the polio vaccine by Jonas Salk ), split (z. B. the influenza vaccine ) or attenuated virions , like the 17D yellow fever vaccine by Max Theiler , the vaccine against the polio virus by Albert Sabin or the Modified Vaccinia Ankara by Anton Mayr .

From the subunit vaccines that went purified antigens (including subunit vaccines , Eng. Subunit vaccines ) as the HBsAg of hepatitis B virus in 1981, conjugate vaccines as against influenzae Haemophilus in 1983 and the synthetically produced peptide vaccines produced, by a Protein purification or, in the latter case, fewer side effects caused by contamination through a peptide synthesis , had less or in the latter case no risk of disease and in which the dose could be adjusted more easily, but which were often less effective in terms of vaccination protection. These vaccines (with the exception of the attenuated pathogens) mainly acted outside the cell on the humoral immune response , as there was only a low uptake in cells and only a low subsequent presentation of the epitopes on MHCI for a cellular immune response .

Marker vaccines

With marker vaccines (synonym DIVA vaccines , from English Differentiating Infected from Vaccinated Animals , differentiating between infected and vaccinated animals), there is no epitope, whereby vaccinated and sick people can be differentiated. The immune reaction against this epitope is absent in vaccinated persons.

literature

Individual evidence

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