Measles, mumps and rubella vs diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b as the most recent vaccine and risk of early ‘childhood asthma’

Abstract

Background and objective Live vaccines may have beneficial non-specific effects. We tested whether the live measles, mumps and rubella (MMR) vaccine compared with the non-live diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine as the most recent vaccine was associated with less childhood asthma and fewer acute hospital contacts for childhood asthma among boys and girls. Methods This study is a nationwide register-based cohort study of 338 761 Danish children born between 1999 and 2006. We compared (i) the incidence of first-registered childhood asthma based on hospital contacts and drug prescriptions and (ii) the incidence of severe asthma defined as acute hospital contacts for childhood asthma between the ages of 15 and 48 months among children whose last received vaccine was three doses of DTaP-IPV-Hib and then MMR with children whose last received vaccine was three doses of DTaP-IPV-Hib. Results For boys, following the recommended vaccine schedule of MMR after DTaP-IPV-Hib3 compared with DTaP-IPV-Hib3 as the last received vaccine, MMR was associated with 8.1 (95% confidence interval 3.9–12.3) fewer childhood asthma cases per 1000 boys, corresponding to 10% (5–15%) reduction in the cumulative incidence of childhood asthma. MMR, when given last, was also associated with 16.3 (95% confidence interval 12.7–20.0) fewer acute hospital admissions for childhood asthma per 1000 boys, corresponding to a 27% (22–31%) reduction in the cumulative incidence. No associations were seen for girls. Conclusion MMR may have a protective effect against childhood asthma for boys. This calls for an understanding of whether non-specific effects of vaccines can be used to optimize our vaccine programmes.

Cohort Profile: Childhood morbidity and potential non-specific effects of the childhood vaccination programmes in the Nordic countries (NONSEnse): register-based cohort of children born 1990–2017/2018

“…5 Most immigration dates were not known, thus all children born abroad were excluded. 6 Date of birth was assigned as a random integer within the month of birth, thus children with date of death or migration within the month of birth is regarded as having no follow-up time in the cohort.…”

“…2 Studies of non-specific effects from highincome countries have primarily focused on infectious disease morbidity 3 and atopic diseases. [4][5][6][7][8] Most of these studies are observational because it would often be unethical to randomise children to refrain from or delay recommended childhood vaccinations. Therefore, concerns about different types…”

Harnessing Mycobacterium bovis BCG Trained Immunity to Control Human and Bovine Babesiosis

“…This paradigm shift sheds light on potential mechanisms for the observed effects that live vaccines have on unrelated pathogens. Of particular interest is the fact that BCG induces TI; however, this observation has also been reported after inoculation with other live vaccines, such as those against measles, smallpox, and the Sabin polio vaccine [47,132]. An important body of work indicates that BCG induces TI in myeloid innate immune cells by epigenetic mechanisms involving DNA methylation, histone modification, and expression of non-coding RNA [53,132].…”

“…Of particular interest is the fact that BCG induces TI; however, this observation has also been reported after inoculation with other live vaccines, such as those against measles, smallpox, and the Sabin polio vaccine [47,132]. An important body of work indicates that BCG induces TI in myeloid innate immune cells by epigenetic mechanisms involving DNA methylation, histone modification, and expression of non-coding RNA [53,132]. In addition, BCG induces metabolic changes in immune and non-immune cells of vaccinated hosts, which may have an impact on how the cells respond to pathogens [44,51,129,130,133].…”