Autumn time is flu time! A reason for many medical doctors to get vaccinated and to take the opportunity to take a look at their vaccination certificate. But what else do you know about tetanus, diphtheria, and co? And how are the different vaccines different in their nature and preparation?

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Active Immunization

This sheme illustrates the process of active immunisation and depends on the original artwork of Invexis

Image: “This sheme illustrates the process of active immunisation and depends on the original artwork of Invexis.” by KoRe78. License: CC BY-SA 3.0

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).

Full vaccines

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).

Subunit vaccines

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).

Toxoid vaccines

Purified toxins, which are (formalin) inactivated for testing purposes (toxoids), are called toxoid vaccines. Examples are the vaccines against tetanus and diphtheria.

Conjugate vaccines

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).

Adjuvants

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 Azellular 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

This sheme illustrates the process of passive immunisation and depends on the original artwork of Invexis

Image: “This sheme illustrates the process of passive immunisation and depends on the original artwork of Invexis.” by KoRe78. License: CC BY-SA 3.0

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 carried out pathogen exposure (postexpositionsprophylaxis / 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
Disease Immunoglobulin Indication
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 Postpartal (until 72h) with rhesus negative mother at the birth of a rhesus-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

vaccine

Image: “Vaccine.” by BruceBlaus. License: CC BY-SA 4.0

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 the stitch channel. 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.

Vaccination complications

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 (Hib)
  • 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.

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