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Active immunization involves the generation of acquired immunity by the application of antigens in the form of
- inactivated pathogens or their components (dead vaccine) or
- pathogens attenuated in their pathogenic effects (virulence), but still proliferative (live vaccines)
Inactivated (killed) vaccines
Inactivated vaccines are weakly immunogenic, which is why multiple applications of the vaccine, as well as regular booster vaccinations, are necessary after successful basic immunization in order to achieve adequate vaccination protection. In addition, they are low in side effects. Undesirable accompanying reactions are mainly due to the addition of adjuvants (see below).
The simplest way of producing dead vaccines is the cultivation of pathogens on specific culture media (bacteria) or within cell cultures or incubated chicken eggs (viruses), followed by physicochemical purification and inactivation by heat or formaldehyde. The full vaccines obtained in this way have all antigenic structures of the pathogen (e.g. rabies vaccine HDC, cholera).
In contrast to full vaccines, subunit vaccines contain pathogen antigens which can be isolated from cultures by purification procedures or can be produced specifically using recombinant DNA technology (e.g., capsular polysaccharides of Haemophilus influenzae type B, pneumococci, meningococci, typhoid).
Purified toxins, which are (formalin) inactivated for testing purposes (toxoids), are called toxoid vaccines. Examples are the vaccines against tetanus and diphtheria.
Polysaccharides produce a weak immunological response based on the T-cell-independent activation of B-cells. In order to ensure lasting immunity with the formation of IgG and immunological memory cells, vaccines have been developed which, by the coupling of polysaccharides to proteins, elicit T-cell-dependent B-cell activation (so-called conjugate vaccines). Conjugate vaccines are available against pneumococci (Prevenar®), group C meningococci, and Haemophilus influenzae type b (Hib).
Because of the low immunogenic potency of many dead vaccines (e.g., toxoid vaccines), active enhancers (e.g., aluminum hydroxide) are added to the purified excitatory antigens which non-specifically enhance the immune response. This is essentially achieved by a locally induced inflammatory reaction, which leads to an increased migration of macrophages, T and B lymphocytes to the site of the pathogen application.
|Examples of dead vaccines|
|Diphtheria||Toxoid vaccine from deactivated diphtheria toxin, contains adjuvant|
|Tetanus||Toxoid vaccine from deactivated tetanus toxin, contains adjuvant|
|Pertussis||Acellular vaccine from different antigens|
|Poliomyelitis||Salk vaccine: Trivalent vaccine containing killed polioviruses from 3 different strains|
|Hepatitis B||Genetically engineered vaccine containing the surface antigen (Hbsag)|
|Hepatitis A||Inactivated viruses|
|Haemophilus Influenzae Type b (Hib)||Conjugate vaccine containing purified capsular polysaccharides|
|Pneumococcus||Conjugate vaccine containing purified capsular polysaccharides|
|Meningococcus||Conjugate vaccine against serotypes A and C, which contains purified capsular polysaccharides|
|Typhoid||Vaccine from purified capsular polysaccharides|
|Cholera||Full vaccine from killed pathogens for intravenous administration|
|FSME||Full vaccine from killed viruses|
|Rabies||Full vaccine from killed viruses|
|Influenza||Gap vaccines from purified antigens (haemagglutinin, neuraminidase)|
Attenuated (Live) Vaccines
Live vaccines are attenuated pathogens in their pathogenic effect (virulence). Most live vaccine strains have been long known. Their pathogenicity loss is due to spontaneous mutations which have developed under the repeated passage of animal host organisms or suitable cell lines.
Through advances in biotechnology, the production of genetically modified attenuated pathogens (e.g., deletion of virulence genes) is also possible more recently.
The reproducibility of the apathogenic pathogens in the vaccinated person leads to a pronounced immune reaction with the formation of a long-lasting immunity. The prerequisite is a functioning immune system, since otherwise unbridled proliferation of the pathogen with the formation of possible vaccination complications can occur. Therefore, live vaccination should not be performed on:
- vaccinees with defects in humoral immunity (B cell defects)
- patients with T cell defects
- patients under chemotherapy
- immunocompromised patients with immunosuppressive therapy (excluding local or low-dose cortisone therapy)
- patients after bone marrow or stem cell transplantation (at least 2 years postinterventionally with sufficient immune status)
For HIV there is a vaccination recommendation for live vaccination, as long as there is no immunosuppression , measured on the CD4 + cell count (see the website of the Robert-Koch-Institute).
|Examples of live vaccines|
|Measles, mumps, rubella, varicella||Vaccines from attenuated viruses|
|Typhoid||Attenuated bacteria to be taken orally (Typhoral)|
|Cholera||Attenuated bacteria to be taken orally|
Passive immunization involves the administration of immunoglobulins to rapidly build up a sufficiently high humoral immunity. Unlike in the case of active immunization, no immunological reaction and no permanent immunity is generated on the part of the vaccine. Rather, the passive immunization will serve as a prophylaxis against an infection after pathogen exposure (postexposure prophylaxis / PEP), whereby, if possible, a simultaneous vaccination with simultaneous active immunization (for example tetanus prophylaxis in unvaccinated injured persons) should be carried out.
Used antibodies are from human (homologous antibodies) or animal (heterologous antibodies) donors:
- Homologous immunoglobulin preparations mainly contain IgG. According to their production, standard immunoglobulins (from a pool of different donors) and hyperimmunoglobulins (from the plasma of donors with high Ak titres) are distinguished. Their average half-life period is 21 days.
- Heterologous antibodies consist of animal proteins and can cause sensitization reactions, whose frame represents the serum disease. Formation of circulating immune complexes can lead to fever, urticaria, arthritides, conjunctivitis and proteinuria. In addition, allergic reactions up to anaphylaxis are described. For this reason, heterologous antisera should be administered exclusively intramuscularly.
|Human immunoglobulins for passive immunization|
|Measles||Human standard immunoglobulin||Immunodeficiency in children|
|Hepatitis A||Human standard immunoglobulin||Contact with infected person|
|Hepatitis B||Human hyperimmunoglobulin||Pathogen Inoculation by needle stick injuries, if there is insufficient Hbs titre (<10 IU / l), postnatal in newborn infants of infected mothers|
|Varizella zoster||Human hyperimmunoglobulin||Protection of the unborn child in case of infection during pregnancy; Immunocompromised persons after exposure|
|Rubella||Human hyperimmunoglobulin||Unvaccinated pregnant women who where exposed to pathogens|
|Rh- intolerance (anti-D-prophylaxis)||Human hyperimmunoglobulin||Postpartum (until 72h) with rh negative mother at the birth of a rh-positive child|
|Tetanus||Human hyperimmunoglobulin||Missing / unknown vaccination protection in case of injuries, simultaneous with active immunization|
|CMV||Human hyperimmunoglobulin||Immune compromised patients|
|Rabies||Human hyperimmunoglobulin||After bite injuries by infected animals|
|Diphtheria||Animal antitoxin||Especially diphteria|
|Botulism||Animal antitoxin||Especially botulism|
Side Effects of Preventive Vaccinations
Regardless of the vaccine used, as a result of the immunological response of the vaccine unpleasant but harmless vaccination reactions can occur which typically develop within the first three days after vaccination. Frequently occurring complaints are local inflammatory reactions (redness, swelling, pain) in the area of injection. More rarely, there is a fever, muscle and joint pain, fatigue and / or flu-like symptoms.
A diminished form of the disease (e.g. vaccination measles, arthralgia in rubella vaccination) is also possible in live vaccinations.
Vaccine complications are vaccine-specific side effects that go beyond the normal and expected vaccination reactions. Their probability of occurrence is very low; data are often based on individual case reports. Regarding the doctor’s duty to inform the patient, however, they are significant.
- anaphylactic reactions (reported in various vaccines)
- Neuritis, neuropathy (diphtheria, tetanus)
- Fever cramps in infants (DPT combination vaccination, measles, mumps, meningococci, pertussis, pneumococcal conjugate vaccine, rubella)
- Guillain-Barré syndrome (FSME, Haemophilus influenzae b, tetanus)
- Encephalitis (TBE, measles)
- Meningitis (mumps)
- Cramps (Hep B)
- Arthritis (MMR vaccination, rubella)
- Thrombocytopenia (pneumococcal polysaccharide vaccine, MMR-V, MMR, MM, influenza, TDaP)
Egg protein allergy
By breeding various vaccines in incubated chicken eggs (measles, mumps, influenza, yellow fever), traces of protein can be present within the vaccines. However, these are usually so marginal as a result of the purification that there is no concern about administration in patients with chicken protein allergy. According to the STIKO Recommendation (2007), contraindication only applies to influenza and yellow fever vaccination.