Bacillus Calmette-Guerin (BCG): the adroit vaccine

Abstract

Background The Bacillus Calmette-Guerin (BCG) vaccine has been in use for 99 years, and is regarded as one of the oldest human vaccines known today. It is recommended primarily due to its effect in preventing the most severe forms of tuberculosis, including disseminated tuberculosis and meningeal tuberculosis in children; however, its efficacy in preventing pulmonary tuberculosis and TB reactivation in adults has been questioned. Several studies however have found that asides from its role in tuberculosis prevention, the BCG vaccine also has protective effects against a host of other viral infections in humans, an effect which has been termed: heterologous, non-specific or off-target. Objectives As we approach 100 years since the discovery of the BCG vaccine, we review the evidence of the non-specific protection offered by the vaccine against viral infections, discuss the possible mechanisms of action of these effects, highlight the implications these effects could have on vaccinology and summarize the recent epidemiological correlation between the vaccine and the on-going COVID-19 pandemic. Results Several epidemiological studies have established that BCG does reduce all-cause mortality in infants, and also the time of vaccination influences this effect significantly. This effect has been attributed to the protective effect of the vaccine in preventing unrelated viral infections during the neonatal period. Some of such viral infections that have been investigated include: herpes simplex virus (HSV), human Papilloma virus (HPV), yellow fever virus (YFV), respiratory syncytial virus (RSV) and influenza virus type A (H1N1). These effects are thought to be mediated via induction of innate immune memory as well as heterologous lymphocytic activation. While epidemiological studies have suggested a correlation, the potential protection of the BCG vaccine against COVID-19 transmission and mortality rates is currently unclear. Ongoing clinical trials and further research may shed more light on the subject in the future. Conclusion BCG is a multifaceted vaccine, with many numerous potential applications to vaccination strategies being employed for current and future viral infections. There however is a need for further studies into the immunologic mechanisms behind these non-specific effects, for these potentials to become reality, as we usher in the beginning of the second century since the vaccine's discovery.

Progressive Host-Directed Strategies to Potentiate BCG Vaccination Against Tuberculosis

“…The research demonstrates the impact of BCG vaccination on the induction of genome-wide histone modifications in trained monocytes which participate in IL-1β generation and the reduction of the yellow fever virus (YFV) burden ( 58 ). BCG-induced protection against YFV infection substantiates the broad-spectrum effectiveness of the vaccine against diverse viral infections such as influenza A (H1N1) virus, herpes simplex virus (HSV), and human papillomavirus (HPV) ( 59 ). Based on this information, BCG vaccination was evaluated initially during the COVID-19 pandemic.…”

Barriers and facilitators to nationwide implementation of the malaria vaccine in Ghana

“…This is comparable to the Bacillus Calmette-Gu é rin (BCG) vaccine implementation in Ghana and Kenya when the efficacy was 56%. Today, the BCG vaccine is accepted globally (Hogan et al, 2020;Adesanya et al, 2021). For previous vaccines introduced in Ghana, the EPI has strengthened its communication to fit the introduction of each vaccine and has shown that acceptance of a new vaccine is dependent on public education and adequate dissemination of evidence (MOH/GHS, 2014).…”

Overwhelming Evidence for a Major Role for Herpes Simplex Virus Type 1 (HSV1) in Alzheimer’s Disease (AD); Underwhelming Evidence against

“…Whichever viruses are involved in AD, one would assume that to prevent their action, specific vaccines would be needed against each one. However, vaccines-in particular Bacillus Calmette Guérin (BCG), which was designed to protect against tuberculosis-have been known since the early years of the 20th century to induce diverse non-specific (offtarget) effects (see reviews [45][46][47]). These effects include reduction of infant mortality independently of its effect on tuberculosis, e.g., in West Africa a 50% reduction in overall mortality was demonstrated in children vaccinated with BCG-too large an effect to be explained by protection against tuberculosis alone [46].…”

“…In the reviews of Pittet and Curtis [47] and Adesanya et al [45], very relevantly to the HSV1-AD concept several studies on the effects of BCG on recurrence of herpes labialis and of genital herpes were analysed. These included Hippman et al [54] who investigated the efficacy of a single intracutaneous BCG injection in preventing recurrent herpes labialis in Tine-test-negative (i.e., negative for infection with M. tuberculosis) subjects, most of whom had had a recurrence rate at least of one per month for many years.…”