Restriction endonuclease analysis was performed on reference strains of each unknown adenovirus subgenus, in comparison with 40 isolates not identified by our routine methods of neutralization with antisera of species 1 to 8. Several uncommon species would not have been identified initially without the assistance of reference laboratories (species 15, 35, and 37). Other species were identified by comparison with published adenovirus DNA restriction endonuclease patterns or from DNA analysis of reference strains (species 31, 40, and 41). Some isolates could not be matched beyond the level of presumptive adenovirus subgenus. Genomic DNA restriction endonuclease analysis of adenoviruses was useful for the identification of adenovirus isolates in a diagnostic virology laboratory. However, accurate interpretation of results will require more extensive DNA restriction endonuclease fragment analysis of a broader range of adenovirus species and genomic variant strains.
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.
Following the discovery of the Bacillus Calmette-Guerin (BCG) vaccine, its efficacy against Mycobacterium tuberculosis was soon established, with several countries adopting universal BCG vaccination schemes for their populations. Soon, however, studies aimed to further establish the efficacy of the vaccine in different populations discovered that the vaccine has a larger effect in reducing mortality rate than could be explained by its effect on tuberculosis alone, which sparked suggestions that the BCG vaccine could have effects on other unrelated or non-mycobacterial pathogens causing diseases in humans. These effects were termed heterologous, non-specific or off-target effects and have been shown to be due to both innate and adaptive immune system responses. Experiments carried out in a bid to further understand these effects led to many more discoveries about the applicability of the BCG vaccine for the prevention, diagnosis, and treatment of certain disease conditions. As we approach the second century since the discovery of the vaccine, we believe it is timely to review these interesting applications of the BCG vaccine, such as in the prevention of diabetes, atherosclerosis, and leukemia; the diagnosis of Kawasaki disease; and the treatment of multiple sclerosis, non-muscle invading bladder cancer, and stage III melanoma. Furthermore, complications associated with the administration of the BCG vaccine to certain groups of patients, including those with severe combined immunodeficiency and HIV, have been well described in literature, and we conclude by describing the mechanisms behind these complications and discuss their implications on vaccination strategies, especially in low-resource settings.
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