Aaby, P., Benn, C.S., Flanagan, K.L.
et al. The non-specific and sex-differential effects of vaccines.
Nat Rev Immunol 20, 464–470 (2020).
https://doi.org/10.1038/s41577-020-0338-x
Abstract
The textbook view of vaccination is that it functions to induce immune memory of the specific pathogen components of the vaccine, leading to a quantitatively and qualitatively better response if the host is exposed to infection with the same pathogen. However, evidence accumulated over the past few decades increasingly suggests that vaccines can also have non-specific effects on unrelated infections and diseases, with important implications for childhood mortality particularly in low-income settings. Furthermore, many of these non-specific effects, as well as the pathogen-specific effects, of vaccines show differences between the sexes. Here, members of the Optimmunize consortium discuss the evidence for and potential mechanisms of non-specific and sex-differential effects of vaccines, as well as their potential policy implications. Given that the non-specific effects of some vaccines are now being tested for their ability to protect against COVID-19, the authors also comment on the broader implications of these trials.
...
Peter Aaby and Christine Stabell Benn. So far, all vaccines tested in epidemiological studies have shown important NSEs on child survival in low-income countries. Observations support a pattern whereby live vaccines (such as smallpox vaccine, BCG vaccine, measles vaccine and oral polio vaccine (OPV)) increase resistance to vaccine-unrelated infections, mainly pneumonia and sepsis, and therefore reduce overall mortality more than would be expected from preventing the vaccine-targeted infections. Hence, these live vaccines have a double benefit in that they prevent both target and non-target infections[SUP]
4[/SUP]. By contrast, non-live vaccines (such as DTP vaccine, the pentavalent vaccine for DTP, hepatitis B virus (HBV) and
Haemophilus influenzae type b, inactivated polio vaccine, single HBV vaccine, the RTS,S/AS01 malaria vaccine, and the H1N1 influenza vaccine) seem to increase susceptibility to vaccine-unrelated infections, particularly in females[SUP]
4[/SUP].
Hence, non-live vaccines may have beneficial effects in preventing the target infection but negative effects by enhancing susceptibility to non-target infections. In epidemiological studies, the negative effects seem to be more pronounced than the beneficial effects, with the net effect being increased overall mortality for females. Fortunately, the most recent vaccine to be administered has the strongest NSEs, and so
the negative effects of non-live vaccines can be at least partly abrogated by providing a live vaccine after the non-live vaccine...
