Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a top killer among infectious diseases. While Bacillus Calmette-Guerin (BCG) is the sole TB vaccine, the clumped-clustered features of BCG in intradermal immunization appear to limit both the BCG protection efficacy and the BCG vaccination safety. We hypothesize that engineering of clumped-clustered BCG into nanoscale particles would improve safety and also facilitate the antigen-presenting-cell (APC)’s uptake and the following processing/presentation for better anti-TB protective immunity. Here, we engineered BCG protoplasts into nanoscale membraned BCG particles, termed as “BCG-Nanocage” to enhance the anti-TB vaccination efficiency and safety. BCG-Nanocage could readily be ingested/taken by APC macrophages selectively; BCG-Nanocage-ingested macrophages exhibited better viability and developed similar antimicrobial responses with BCG-infected macrophages. BCG-Nanocage, like live BCG bacilli, exhibited the robust capability to activate and expand innate-like T effector cell populations of Vγ2+ T, CD4+ T and CD8+ T cells of rhesus macaques in the ex vivo PBMC culture. BCG-Nanocage immunization of rhesus macaques elicited similar or stronger memory-like immune responses of Vγ2Vδ2 T cells, as well as Vγ2Vδ2 T and CD4+/CD8+ T effectors compared to live BCG vaccination. BCG-Nanocage- immunized macaques developed rapidly-sustained pulmonary responses of Vγ2Vδ2 T cells upon Mtb challenge. Furthermore, BCG- and BCG-Nanocage- immunized macaques, but not saline controls, exhibited undetectable Mtb infection loads or TB lesions in the Mtb-challenged lung lobe and hilar lymph node at endpoint after challenge. Thus, the current study well justifies a large pre-clinical investigation to assess BCG-Nanocage for safe and efficacious anti-TB vaccination, which is expected to further develop novel vaccines or adjuvants. Graphical Abstract

Bacillus Calmette-Guerin Vaccine-Associated Lymphadenitis in Children

Background: Tuberculosis (TB) is one of the most important infectious diseases worldwide. Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine, entered into the childhood immunization program by the World Health Organization (WHO) in 1974 to prevent TB. One of the relatively common complications of BCG vaccination is regional lymphadenitis. Objectives: This study aimed to determine the lymphadenitis incidence in BCG-vaccinated children in southwest Iran. Methods: In a prospective descriptive study, infants born from March to June 2017 were evaluated for BCG vaccine complications at two, four, six, nine, and 12 months of age in Ahvaz, southwestern Iran. Results: The study enrolled 1,506 infants (794 males and 712 females). Among the vaccinated infants, four (0.26%) had injection site reactions, and 106 (7.03%) presented lymphadenitis (66 males and 40 females). The lymphadenitis rate was significantly higher in males than in females (P = 0.024). The mean age at presentation was 4.28 ± 0.79 months. Suppurative lymphadenitis was seen in 53 (50%) cases and nonsuppurative lymphadenitis in 53 (50%) cases. About 80% of nonsuppurative lymphadenitis resolved entirely or partially after a one-year follow-up. Of 53 cases with suppurative lymphadenitis, 46 (43.4%) developed spontaneous drainage, and seven (6.6%) were drained by needle aspiration. No significant relationship was found between the BCG inoculation site and lymphadenitis rate. No other complications such as osteomyelitis or disseminated BCG infection were observed after one year of follow-up. Conclusions: The relatively high incidence of BCG lymphadenitis in this study may be due to the vaccine strain, young vaccinees, and improper vaccination techniques. In most cases, nonsuppurative lymphadenitis regressed spontaneously, and suppurative lymphadenitis was drained spontaneously or by needle aspiration.

Characteristics of severely malnourished under-five children immunized with Bacillus Calmette-Guérin following Expanded Programme on Immunization schedule and their outcomes during hospitalization at an urban diarrheal treatment centre, Bangladesh

Background Bacillus Calmette-Guérin (BCG) vaccination has recently been found to have beneficial effects among children infected other than Mycobacterium tuberculosis. Due to the paucity of data on the outcomes of children who had successful BCG vaccination following Expanded Programme on Immunization (EPI) schedule, we aimed to investigate the characteristics of such children and their outcomes who were hospitalized for severe malnutrition. Methods A prospective observational study was conducted to determine the viral etiology of pneumonia in severely malnourished children those were admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between April 2015 and December 2017, constituted the study population. Using a case-control design for the analysis, children having BCG vaccination prior hospital admission were treated as cases (n = 611) and those without vaccination, constituted as controls (n = 83). Bi-variate analysis was conducted using socio-demographic, clinical, laboratory, and treatment characteristics on admission and outcomes during hospitalization. Finally, log-linear binomial regression analysis was done to identify independent impact of BCG vaccination. Results The cases more often presented with older age, have had lower proportion of maternal illiteracy, higher rate of breastfeeding, severe wasting and lower rate of hypoglycemia, compared to the controls. The cases were also found to have lower risk of severe sepsis and deaths, compared to the controls (for all, p<0.05). However, in log-linear binomial regression analysis, after adjusting for potential confounders, BCG vaccination following EPI schedule (RR:0.54; 95%CI = 0.33–0.89; p = 0.015) and breastfeeding (RR:0.53; 95%CI = 0.35–0.81; p = 0.003) were found to be protective for the development of severe sepsis. Conclusion BCG vaccination and breastfeeding were found to be protective for the development of severe sepsis in hospitalized severely malnourished under-five children which underscores the importance of continuation of BCG vaccination at birth and breastfeeding up to two years of age.

Tuberculosis, BCG Vaccination and COVID-19: Are They Connected?

Evidence from multiple scientific studies suggests that the Bacillus Calmette–Guérin (BCG) vaccine, widely used worldwide as a preventive measure against tuberculosis, also offers cross-protection against other pathogens. This review aimed to gather data from research that studied the mechanisms involved in the immunological protection induced by the BCG vaccine, which may be important in the control of viral infections, such as COVID-19. Through a literature review, we compiled information about the different BCG strains used worldwide, as well as the responses and protection elicited by them. We commented on the mechanisms of immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and we discussed the possibility of cross-protection of different BCG strains on the control of COVID-19. Due to the immunomodulatory properties of BCG, some BCG strains were able to induce an effective cellular immune response and, through epigenetic modifications, activate cells of the innate immune system, such as monocytes, macrophages and natural killer cells, which are crucial for the control of viral infections. Although several vaccines have already been developed and used in an attempt to control the COVID-19 pandemic, some BCG vaccine strains may help stimulate the basal defences against these pathogens and can be used as additional defences in this and future pandemics.

Transurethrale Resektion von Blasentumoren (TUR-B)

ZusammenfassungDie transurethrale Resektion von Blasengewebe (TUR-B) ist für die Diagnostik und Therapie bei Blasentumoren indiziert. Diese werden fragmentiert mittels diathermaler Schlinge abgetragen. Der Wundgrund wird zur Blutstillung koaguliert. Zu achten ist auf eine ausreichende Schnitttiefe, sodass die Detrusormuskulatur erfasst ist. Postoperativ kann zur Rezidivprophylaxe eine intravesikale Single-shot-Chemotherapie verabreicht werden. Methoden zur verbesserten Tumorvisualisation (insbesondere photodynamische Diagnostik) helfen, besonders bei multilokulärem Befund oder Carcinoma in situ (CIS) bessere Detektionsraten zu erreichen sowie das Rezidiv- und Progressionsrisiko zu senken. In Abhängigkeit von der Histologie ergibt sich das weitere Vorgehen: bei nicht muskelinvasivem Blasenkarzinom Nachsorge, adjuvante Instillationstherapie mittels Chemotherapie oder Bacillus Calmette-Guérin (BCG), die Nachresektion („second look TUR-B“), die Frühzystektomie oder bei muskelinvasivem Blasenkarzinom die Zystektomie oder (onkologisch nachrangig) die trimodale Therapie mit erneuter TUR‑B, Radiotherapie und Chemotherapie. Mögliche Komplikationen im Rahmen der TUR‑B sind v. a. Nachblutung mit Blasentamponade, extra- oder intraperitoneale Blasenperforation oder Infektionen des Urogenitaltrakts.