Heterologous effects

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Heterologous effects (including unspecific effects , off-target effects or non-specific effects ) occur with vaccinations . They are characterized by the fact that they go beyond the pathogen-specific effects intended and anticipated for vaccinations (protective effect against the respective target disease) and can have an impact on overall morbidity (also generally against non-vaccinated diseases) and mortality . This effect is particularly pronounced in countries where many children die from infectious diseases.

Positive effects with live vaccines

Several epidemiological studies as well as studies from developing countries have shown that child mortality was reduced by 40% after a measles vaccination , and more children were saved than had died before the vaccinations. This additional reduction cannot be caused by avoiding the disease itself. In z. B. Congo , Senegal and Guinea-Bissau , it even fell by 50% after vaccinations started, far more than would have been expected by preventing measles-related mortality.

This effect could also be shown with other live vaccinations . For example, overall mortality in children vaccinated with BCG declines more sharply than expected in the first 6–12 months compared with children not vaccinated with BCG. There are similar references to the MMR vaccination , the oral polio vaccination ( OPV ) and the smallpox vaccination at the time .

These positive, unspecific effects after a live vaccination occur more clearly in childhood. Apparently the immune system is stimulated by the vaccination and an innate immune memory develops (“immune training”). In the event of a measles infection , it would be deleted again (immunosuppression by eliminating the B and T cells ). Live vaccines also stimulate the activation of T cells, which develop a cross-reactive potential ("cross protection"). The cross-protection could partly be reproduced in cell and animal studies . Positive heterologous effects can be explained immunologically and are plausible. Vaccinations mimic a real infection (with a far lower risk of a real illness) and as a result stimulate helpful, unspecific effects, also generally against other illnesses. If the immune system is later specialized and fully functional, unspecific effects no longer play a major role.

The positive effects are particularly evident in countries where many children die of infectious diseases , for example in Guinea-Bissau. In addition, children in those countries are often infested with parasites , which can influence unspecific effects. In industrialized nations this effect may be less, for example after a BCG or MMR vaccination. The Danish anthropologist and medical scientist Peter Aaby suspects that the elimination of live vaccinations such as the smallpox vaccination or BCG has even increased the risk of allergies , since the relevant immune training has failed.

There is evidence that gender has an influence on the heterologous effects. Apparently the measles, BCG and smallpox vaccinations have a stronger positive effect on girls than on boys, while the OPV, conversely, favor boys. The exact reason for the gender difference is not known.

Postulated negative effects with dead vaccines

In addition to the known positive heterologous effects after live vaccinations, negative heterologous effects after administration of dead vaccines - especially DTP - were postulated in observational studies by Aaby in Guinea-Bissau, West Africa . While Aaby certainly confirms the positive effects after live vaccinations, the DTP vaccine protects effectively against the corresponding diseases, but is also said to increase child mortality in girls from other diseases. However, if a live vaccine (e.g. BCG or the maser vaccine) is given parallel to or shortly after administration of the inactivated vaccine, these negative effects should cancel out or at least be greatly reduced. The last vaccine given should be decisive. Aaby therefore recommends that the basic immunization should be completed with a live vaccination and that more immunization should generally be carried out with live vaccines.

These data are being questioned by the WHO . The STIKO also sees no reason to change the vaccination plans in Germany (also with regard to possible positive effects). The WHO, but also other vaccination experts, criticize the fact that Aaby's studies have methodologically significant limits; these studies are also regionally limited in sub-Saharan Africa , where infectious diseases are a major contributor to child mortality. A review from 2016 examined cohort studies and came to very different results; the authors pointed out that there was a high risk of bias. In addition, in contrast to the positive heterologous effects, there is no immunologically plausible explanation for the negative effects of dead vaccines.

Web links

Individual evidence

  1. ↑ Barbara Bröker, Christine Schütt, Bernhard Fleischer: Basic knowledge of immunology . Springer-Verlag, 2019, ISBN 978-3-662-58330-2 , pp. 186-187 .
  2. ↑ a b c d e f What is meant by non-specific effects of vaccinations? In: RKI. August 21, 2018, accessed March 8, 2020 .
  3. ↑ a b Barbara Bröker, Christine Schütt, Bernhard Fleischer: Basic knowledge of immunology . Springer-Verlag, 2019, ISBN 978-3-662-58330-2 , pp. 250-251 .
  4. ↑ a b c d e f g h Nina Weber: "Inoculated" - Peter Aaby: What are unspecific effects of vaccinations? In: Der Spiegel . September 11, 2018, accessed March 8, 2020 .
  5. ↑ Peter Aaby, Hilton Whittle, Christine Stabell Benn: Vaccine programs must consider their effect on general resistance . In: BMJ . tape 344 , June 14, 2012, p. e3769 , doi : 10.1136 / bmj.e3769 , PMID 22700785 .
  6. ↑ Lone Graff Stensballe et al .: BCG vaccination at birth and early childhood hospitalization: a randomized clinical multicenter trial . In: Archives of Disease in Childhood . tape 102 , no. 3 , March 1, 2017, p. 224-231 , doi : 10.1136 / archdischild-2016-310760 , PMID 27443836 .
  7. ↑ Susanne MAJ Tielemans et al .: Non-specific effects of measles, mumps, and rubella (MMR) vaccination in high income setting: population based cohort study in the Netherlands . In: The BMJ . tape 358 , August 30, 2017, doi : 10.1136 / bmj.j3862 , PMID 28855159 , PMC 5576097 (free full text).
  8. ↑ Olaf Müller and Heiko Becher: International Health: Non-specific effects of vaccinations. In: Deutsches Ärzteblatt . October 9, 2015, accessed March 8, 2020 .
  9. ↑ a b Non-specific vaccination effects: Training for the immune system. In: Pharmaceutical newspaper . September 5, 2018, accessed March 8, 2020 .
  10. ↑ LCJ de Bree et al .: Non-specific effects of vaccines: Current evidence and potential implications . In: Seminars in Immunology . tape 39 , October 2018, p. 35-43 , doi : 10.1016 / j.smim.2018.06.002 , PMID 30007489 .
  11. ^ A b Babita Agrawal: Heterologous Immunity: Role in Natural and Vaccine-Induced Resistance to Infections . In: Frontiers in Immunology . tape 10 , 2019, ISSN  1664-3224 , p. 2631 , doi : 10.3389 / fimmu.2019.02631 , PMID 31781118 , PMC 6856678 (free full text).
  12. ↑ INCREASED MORTALITY AFTER DEAD VACCINES? In: arznei-telegram . November 18, 2016, accessed March 11, 2020 .
  13. ^ Julian PT Higgins et al .: Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review . In: BMJ . tape 355 , October 13, 2016, doi : 10.1136 / bmj.i5170 , PMID 27737834 .