Heterologous Effects of Infant BCG Vaccination: Potential Mechanisms of Immunity

Abstract

The current antituberculosis vaccine, BCG, was derived in the 1920s, yet the mechanisms of BCG-induced protective immunity and the variability of protective efficacy among populations are still not fully understood. BCG challenges the concept of vaccine specificity, as there is evidence that BCG may protect immunized infants from pathogens other than Mycobacterium tuberculosis – resulting in heterologous or nonspecific protection. This review summarizes the up-to-date evidence for this phenomenon, potential immunological mechanisms and implications for improved childhood vaccine design. BCG induces functional changes in infant innate and adaptive immune compartments, encouraging their collaboration in the first year of life. Understanding biological mechanisms beyond heterologous BCG effects is crucial to improve infant protection from infectious diseases.

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“…There has already been evidence showing that the BCG vaccine not only provides protection against tuberculosis, but also has a so-called heterologous immunomodulatory effect, which results in protection against various viral infections as well [5][6][7]. Its exact mechanism is not yet fully understood, but involves the activation of both heterologous lymphocytes and the trained immune system resulting in lower rates of neonatal sepsis and respiratory tract infections [5,6]. Protection of BCG vaccination against viral infections has also been described for Herpes and Influenza viruses [8].…”

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“…The population that has been previously shown to benefit from BCG-induced heterologous immunity is restricted to the pediatric population. [10][11][12][13][14][15][22][23] Furthermore, this benefit seems to only be apparent when the regions involved already have high childhood mortality, as evidenced by the Danish Calmette Study. 16 The pediatric population can contract COVID-19 and even serve as potential carriers .…”

“…10,11 This reduction in mortality has been found to be more noticeable in regions with high childhood mortality and infectious disease burden such as West Africa. 12,13 Similarly, the rates of infection by non . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

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“…It has been hypothesized that live vaccines may reduce infant mortality by direct enhancement of innate immune protection, whereas nonlive vaccines may do the opposite. There is substantial evidence that these effects are generally stronger in females than in males [69]. Another idea is that the vaccine-mediated heterologous protection would be partly mediated by heterologous effects on the adaptive immunity and by potentiating innate immune responses through epigenetics [70].…”