Progress in research on novel BC adjuvant system / 中国生物制品学杂志

@#Vaccines with novel adjuvants have been listed abroad,while in China,except for aluminum adjuvants widely used in vaccine research and production,few other novel adjuvants have been successfully listed. This paper briefly summarized the source,development history,research progress on biological activity and immune mechanism as well as safety evaluation of the novel BC adjuvant system with independent intellectual property right which has been applied to the vaccine in clinical research stage,so as to provide theoretical support for selection of the adjuvant in the development of novel vaccine.

CRX-527 as a candidate adjuvant in a recombinant BCG-based malaria vaccine

@#Abstract: Objective: To investigate the role of CRX-527, a Toll-like receptor 4 agonist, as the possible adjuvant for recombinant Mycobacterium bovis Bacillus Calmette-Guerin expressing merozoite surface protein 1C (BCG-MSP-1C). Methods: The mice were immunized with BCG and BCG-MSP- 1C in the presence and absence of CRX-527. The untreated mice (injected with PBS-T80 only) were the negative control. The ability of CRX-527 to enhance IgG and its subclasses, as well as IL-4 and IFN-γ production in the serum and spleen supernatant was evaluated using ELISA. Results: Mice immunized with BCG-MSP-1C exhibited the highest production of IgGs, IL-4 and IFN-γ after third immunization. In addition, CRX-527 further promoted the production of total IgG and IgG subclasses as well as IFN-γ and IL-4 in the serum and splenocytes of immunized mice. Conclusions: CRX-527 has the potential as an adjuvant candidate for the candidate vaccines. Further study is needed to verify appropriate dosage for immunization and its efficacy.

Increased risk of bladder cancer recurrence due to bacillus Calmette-Guérin shortage in Brazil

SUMMARY OBJECTIVE: Our study aimed to evaluate the impact of bacillus Calmette-Guérin shortage on recurrence and progression in patients with non-muscle invasive bladder cancer in a Brazilian cohort. METHODS: We retrospectively reviewed the clinicopathological data of 409 patients who had their first transurethral resection of the bladder tumor for intermediate or high-risk non-muscle invasive bladder cancer between June 2014 and May 2021 in a tertiary public hospital in Brazil. Patients included had non-muscle-invasive urothelial carcinoma of the bladder resected completely for the first time, regardless of bacillus Calmette-Guérin use. Low-risk disease patients were excluded from the analysis. Demographic, clinicopathological, and bacillus Calmette-Guérin use data were collected from our database. Recurrence and progression data were obtained from patient records or through telephone interviews. Recurrence-free survival and progression-free survival were calculated from the date of transurethral resection of the bladder tumor until the events of recurrence, progression, last office visit, or phone interview. RESULTS: Within a median follow-up period of 26.7 months, 168 (41.1%) patients experienced a recurrence in a median time of 27 months (95%CI 16.1-38). Bacillus Calmette-Guérin was administered to 57 (13.9%) individuals after transurethral resection of the bladder tumor. Patients with ≥3 lesions (p<0.001), those with lesions >3 cm (p=0.02), and those without bacillus Calmette-Guérin treatment (p<0.001) had shorter recurrence-free survival. According to a Cox multivariate regression model, bacillus Calmette-Guérin use was independently associated with a reduced recurrence rate, with an HR of 0.43 (95%CI 0.25-0.72). Out of the patients studied, 26 (6.4%) experienced progression. T1 stage (p<0.001) and high-grade (p<0.001) were associated with shorter progression-free survival. Bacillus Calmette-Guérin did not influence bladder cancer progression. In the Cox multivariate analysis, high-risk disease was independently associated with progression (p<0.001). CONCLUSION: Our study confirms that non-muscle invasive bladder cancer exhibits a high recurrence rate. The use of adjuvant bacillus Calmette-Guérin in intermediate and high-risk patients significantly reduces this rate. Furthermore, the bacillus Calmette-Guérin shortage could have negatively impacted these patients.

Vacunación de BCG en el medio rural y la importancia del conocimiento de sus beneficios / BCG vaccination in rural areas and the importance of knowledge of its benefits

Objetivo General: Establecer nivel de conocimiento sobre tuberculosis y vacuna, BCG., de padres y representantes, en Ambulatorio Gabriel Trompiz, Tucacas, Estado Falcón. Metodología: Es un estudio descriptivo de tipo transversal, con una muestra poblacional de 180 madres, padres y representantes entre octubre y diciembre de 2022. Se utilizaron encuestas, formularios elaborados y validados en estudios anteriores; la información fue procesada con el programa estadístico Microsoft Excel. Resultados: la mayor parte de la población respondió que la tuberculosis es una enfermedad producida por un virus, con respecto a la importancia de las inmunizaciones, un 20% desconocía la importancia de la vacunación. El 77% conocían información básica acerca de la vacuna BCG. En cuanto a las enfermedades prevenibles por esta vacuna, un 54% respondió que se trataba sobre la tuberculosis, mientras que casi la mitad de la población estudiada tenía la creencia que tenía que ver con el resfriado común. El 72% de la población considera que la fiebre es una contraindicación para la aplicación de la vacuna BCG. Se demostró que existía una gran desinformación con respecto a la vacunación en la población infantil en el medio rural venezolano(AU)

To establish the level of knowledge about tuberculosis and BCG vaccine., of parents and representatives in the Gabriel Trompiz outpatient clinic, Tucacas, Falcon State. Methodology: it is a descriptive cross-sectional study, with a population sample of 180 mothers, fathers and representatives between October and December 2022. Surveys, forms prepared and validated in previous studies were used, the information was processedwith the Microsoft Excel statistical program. Results: most of the population answered that tuberculosis was a disease caused by a virus, regarding the importance of immunizations, 20% were unaware of the importance of vaccination. 77% knew basic information about the BCG vaccine. Regarding the diseases preventable by this vaccine, 54% answered that it was about tuberculosis, while almost half of the population studied believed that it had to do with the common cold. 72% of the population considers that fever is a contraindication for the application of the BCG vaccine. It was demonstrated that there was a great amount of misinformation regarding vaccination in the child population in rural Venezuela(AU)

Cardiorespiratory Adverse Events after First Vaccination in Preterm Neonates With Gestational Age ?30 Weeks

Objectives: To document the adverse cardiorespiratory events following first routine immunization in preterm neonates. Methods: We retrieved records of neonates with gestational age ?30 weeks, and included those who developed cardiorespiratory events after first vaccines before discharge. Our Unit’s protocol is to administer Bacillus Calmette-Guerin (BCG), hepatitis B vaccine to those discharged at <8 weeks postnatal age. Hexavalent, BCG, pneumococcal vaccine and rotavirus vaccines are given at 8 weeks of age, if hospital stay is predicted to be longer. Unit compliance to vaccination administration at appropriate ages were also measured. Results: Data of 161 neonates ?30 weeks (17.4% <27 week) who completed care in the unit was studied. Cardio-respiratory adverse events were reported in 21(13.7%). None of these required initiation of invasive ventilation. High flow nasal cannula therapy and caffeine restart were required for these events in 14 (9.3%) and 6 (3.9%) neonates, respectively. Lower gestational age, bronchopulmonary dysplasia and sepsis were significant risk factors on univariate analysis. On multivariate analysis, continued need for respiratory support at 4 weeks of age (P=aOR 14.5 (95% CI 5-59.1) was the only independent risk factor for post-vaccination cardiorespiratory adverse events. Of 38 who were not vaccinated at recommended ages by unit policy, 25 were missed opportunities, the rest were deemed unstable for vaccinations at that age by the clinical team. Conclusion: Adverse cardiorespiratory events were uncommon after first vaccinations in very preterm neonates. Administering vaccines in this group before discharge would allow monitoring for these events, especially for those who require long-term respiratory support.

Implications of the non-specific effect induced by Bacillus Calmette-Guerin (BCG) vaccine on vaccine recommendations

Abstract Objectives: Since the beginning of its use for the prevention of tuberculosis (TB) in 1921, other uses of BCG (Bacillus Calmette-Guérin) have been proposed, particularly in the treatment of malignant solid tumors, multiple sclerosis, and other autoimmune diseases. Its beneficial impact on other infections, by nontuberculous mycobacteria, and by viruses, has been more often studied in recent years, especially after the introduction of the concept of trained immunity. The present study's objective was to review the possible indications of BCG and the immunological rationale for these indications. Data source: Non-systematic review carried out in the PubMed, SciELO and Google Scholar databases, using the following search terms: "BCG" and "history", "efficacy", "use", "cancer", "trained immunity", "other infections", "autoimmune diseases". Data synthesis: There is epidemiological evidence that BCG can reduce overall child morbidity/mortality beyond what would be expected from TB control. BCG is able to promote cross-immunity with nontuberculous mycobacteria and other bacteria. BCG promotes in vitro changes that increase innate immune response to other infections, mainly viral ones, through mechanisms known as trained immunity. Effects on cancer, except bladder cancer, and on autoimmune and allergic diseases are debatable. Conclusions: Despite evidence obtained from in vitro studies, and some epidemiological and clinical evidence, more robust evidence of in vivo efficacy is still needed to justify the use of BCG in clinical practice, in addition to what is recommended by the National Immunization Program for TB prevention and bladder cancer treatment.

Revisiting the Chingleput BCG vaccination trial for the impact of BCG revaccination on the incidence of tuberculosis disease

Background & objectives: Vaccines play a crucial role in the prevention of tuberculosis (TB). Revaccination with Bacille Calmette–Guerin (BCG) for the prevention of TB is an important strategy that is currently gaining interest. The objective of this study was to reanalyze the community-based Chingleput BCG vaccination trial for protective efficacy of BCG revaccination against incident TB disease. Methods: A retrospective analysis of the Chingleput BCG vaccination trial (conducted in 1968) data was carried out. Data on participants with evidence of prior BCG vaccination at trial intake and randomized to BCG vaccine [low dose (0.01 mg), high dose (0.1 mg)] and placebo arms were analyzed. The incidence of TB disease, which was based on sputum culture and/or chest X-ray was compared between the BCG and placebo arms over a 15 yr follow up period. Results: Of the 269,727 individuals randomized in the trial; 263,158 had no evidence of TB at baseline, of which 4436 (1.68%) had evidence of BCG vaccination at trial intake (2890 in the BCG vaccine and 1546 in the placebo arms, respectively). There were 77 (190 per 100,000) and 64 (296 per 100,000) incident TB cases in the BCG and placebo arm, respectively, at 15 yr post-vaccination. The incidence of TB disease was significantly lower in the BCG arm [Hazard ratio of BCG arm (95% confidence interval): 0.64 (0.46-0.89)]. Interpretation & conclusions: Retrospective data analysis of this community-based trial revealed that BCG revaccination in a community offered modest protection against the development of TB disease at the end of 15 years which, however, requires further evaluation.

Eventos adversos sistémicos post-vacuna BCG. Serie de casos pediátricos / Systemic adverse events post-BCG vaccine. Pediatric case series

La vacuna BCG es clave para el control de la tuberculosis. En ocasiones se observan eventos adversos sistémicos causados por Mycobacterium bovis BCG; usualmente asociados a inmunodeficiencia. Describimos seis casos clínicos de niños vacunados con BCG al nacer, con complicaciones sistémicas post-vacunación. M{ETODO: Revisión de historias clínicas de pacientes con infección por M. bovis BCG atendidos en un hospital pediátrico, entre 2010 y 2019. RESULTADOS: De 400 casos confirmados de infecciones por complejo Mycobacterium tuberculosis; ocho fueron identificados como M. bovis BCG; seis casos correspondieron a eventos adversos sistémicos post-vacuna BCG: dos con lesiones cutáneas a distancia, dos osteomielitis y dos infecciones generalizadas. En cinco de los seis pacientes se detectó una alteración de la respuesta inmune. Un paciente falleció por falla multiorgánica, uno se derivó y cuatro completaron 12 meses de tratamiento: dos meses de isoniacida, rifampicina, etambutol, y moxifloxacina, y 10 meses de isoniacida y rifampicina. Tuvieron buena tolerancia a los medicamentos, sin recaída a los dos años. CONCLUSIÓN: La infección grave por M. bovis BCG es una rara complicación sistémica de la vacunación. Es razonable buscar defectos inmunológicos en los niños que desarrollan este tipo de eventos adversos.

The BCG vaccine is key to tuberculosis control. Systemic adverse events caused by Mycobacterium bovis BCG are occasionally observed; usually associated with immunodeficiency. In this report we describe six cases of children vaccinated with BCG at birth, with post-vaccination systemic complications. METHOD: retrospective review of medical records of patients with M. bovis BCG infection treated in a pediatric hospital between 2010 and 2019. RESULTS: Of 400 confirmed cases of Mycobacterium tuberculosis complex infection, eight identified as M. bovis BCG, six corresponded to systemic adverse events post-BCG vaccine: two distant skin lesions, two osteomyelitis and two generalized infections. An altered immune response was detected in five of the six patients. One patient died of multiorgan failure, one was referred and four completed 12 months of treatment: two months of isoniazid, rifampin, ethambutol, and moxifloxacin, and 10 months of isoniazid and rifampin. They had good tolerance to medications, without relapse at two years. CONCLUSION Serious M. bovis BCG infection is a rare systemic complication of vaccination. It is reasonable to look for immunological defects in children who develop these types of adverse events.

Genome sequencing and analysis of BCG strain for vaccine production in China / 上海预防医学

ObjectiveTo conduct the sequencing and preliminarily analysis of the whole genome of BCG Shanghai D2PB302 strain （hereinafter referred to as BCG Shanghai D2 strain）， which has been used exclusively for the vaccine production in China. MethodsThe DNA of of BCG Shanghai D2 strain （D2-JIA12-1） was extracted， and the whole genome was sequenced by Pacbio-RS Ⅱ. The sequence data was assembled by Smrtlink and polished with the illumina data. Genes， tRNA and rRNA were predicted based on the sequence data. The functional annotation of predicted genes was performed through BLASTP. The IVE-TB antigen gene and MTBVAC were selected as the target sequences to be compared with Mycobacterium tuberculosis H37Rv （NC_000962.3）. ResultsThe sequence length of BCG Shanghai D2 strain was 4 045 232 bp， and the GC content was 65.66%. A total of 4 259 protein-encoding genes were predicted， with an average gene size of 933 bp. 2 476 genes had biological functions and others were hypothetical proteins.144 virulence genes were obtained by comparing with the VFDB. There were 29 type Ⅶ secretion system genes and 10 PE/PPE protein family genes. ConclusionThe whole genome sequence of BCG Shanghai D2 strain is clarified. It lays a broad foundation for subsequent detection of the stability of major antigen genes.

Advances in Bacillus Calmette-Guerin / 中国生物制品学杂志

@#Tuberculosis(TB) is a chronic and debilitating infectious disease caused by Mycobacterium tuberculosis(Mtb). It is a significant health concern that poses a serious threat to human well-being. Bacillus Calmette-Guerin(BCG)is the only approved vaccine for the prevention of TB. BCG is made from attenuated bovine Mtb and is highly effective in preventing tuberculous meningitis and granulomatous TB,which are particularly lethal in infants. However,BCG provides limited protection in both children and adults,and this protective effect decreases over time. Currently,there are ongoing improvements being made to BCG,which involve modifications in immunization routes and procedures. Additionally,researchers are working on the development of new TB vaccines. BCG is primarily used for the prevention of TB and the treatment of bladder cancer,although it also has other indications. This paper reviewed the recent research progress of BCG,focusing on its development history,improvements,and indications.

Use of a catch-up programme to improve routine immunization in 13 provinces of Papua New Guinea, 2020–2022

@#Objective: Routine immunization coverage in Papua New Guinea has decreased in the past 5 years. This persistently low routine immunization coverage has resulted in low population immunity and frequent outbreaks of vaccine-preventable disease across the country. We describe the use of a catch-up programme to improve routine immunization during the coronavirus disease pandemic in Papua New Guinea during 2020–2022. Methods: In June 2020, 13 provinces of Papua New Guinea were selected to undergo a vaccination catch-up programme, with technical support from the World Health Organization (WHO) and the United Nations Children’s Fund. Twelve provinces received financial and logistic support through the Accelerated Immunization and Health Systems Strengthening programme, and one received support from WHO. All stakeholders were involved in planning and implementing the catch-up programme. Results: Between July 2020 and June 2022, about 340 health facilities conducted catch-up activities. The highest number of children aged under 1 year were vaccinated in 2022 (n = 33 652 for third dose of pentavalent vaccine). The national coverage of routine immunization (including the catch-up vaccinations) increased between 2019 and 2020 – by 5% for the third dose of pentavalent vaccine, 11% for the measles-rubella vaccine and 16% for the inactivated poliovirus vaccine. The coverage declined slightly in 2021 before increasing again in 2022. Discussion: The catch-up programme was an instrumental tool to improve routine immunization coverage between 2020 and 2022 and during the pandemic in Papua New Guinea. With appropriate technical and logistic support, including financial and human resources, catch-up programmes can strengthen routine immunization coverage across the country.

BCG + piroxicam versus BCG + gemcitabine for prevention of postoperative recurrence in intermediate- and high-risk bladder cancer and effects on serum AGR and PON1 / 中国临床药理学与治疗学

AIM: To investigate the effect of BCG + piroxicam versus BCG + gemcitabine in the prevention of postoperative recurrence in intermediate - to high-risk bladder cancer and the effect on serum albumin / globulin ratio (AGR) and paraoxonase 1 (PON1). METHODS: Eighty patients with medium-high risk bladder cancer in our hospital from October 2021 to April 2022 were randomly divided into two groups with 40 cases each. Both groups received transurethral resection of bladder tumor. The control group received postoperative bladder perfusion of pirubicin combined with BCG vaccine, and the study group received postoperative bladder perfusion of gemcitabine combined with BCG vaccine. The therapeutic effect, serum tumor markers secretory protein Dickkopf (DKK), bladder cancer specific nuclear matrix protein-1 (BLCA-1), β2-microglobulin (β2-MG), new angiogenesis factorsvascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), AGR and PON were compared between the two groups 1. Level, quality of lifeCore Quality of Life Questionnaire Scale (EORTC QLQ-C30), functional status Functional status Scoring Scale (KPS), adverse reactions, The recurrence rates at 1 year after surgery were compared between the two groups. RESULTS: The total effective rate of the study group was 92.50%(37/40) higher than that of the control group 75.00%(30/40) (P<0.05). The serum levels of DKK, BLCA-1, β2-MG, VEGF, FGF and AGR in the study group were lower than those in the control group at 1 month, 3 months and 6 months after surgery, while the level of PON1 was higher than that in the control group (P<0.05). The EORTC QLQC30 and KPS scores of the study group were higher than those of the control group at 1, 3 and 6 months after surgery (P<0.05). The incidence of nausea/vomiting, diarrhea, leukopenia and cystitis in the study group was lower than that in the control group (P<0.05). The recurrence rate of the study group 1 year and 2 years after surgery was lower than that of the control group (P<0.05). CONSLUSION: Compared with pirubicin combined with BCG vaccine, gemcitabine combined with BCG vaccine is more effective in the treatment of middle and high-risk bladder cancer, which can inhibit tumor angiogenesis, regulate AGR and PON1 levels, prevent postoperative recurrence, improve quality of life, improve functional status, and have higher safety.

Protective effects of BCG / 公共卫生与预防医学

BCG vaccine is one of the most widely used vaccines in human history, with tens of billions of doses administered annually over the past century as an important means of preventing tuberculosis. However, BCG is also used for non-traditional purposes of prevention and treatment, such as bladder cancer immunotherapy. In addition to cancer immunotherapy, BCG is increasingly found to be helpful for a variety of immune diseases, including multiple sclerosis, typeⅠdiabetes, and some atopic diseases. It also can protect against non-tuberculous mycobacterium infections, viral infections and even COVID-19. This allogenic protective effect lies in the BCG vaccine's ability to alter immune set points through allogenic T cell immunity, as well as in the epigenetic and immunological effects of metabolomic changes in innate immune cells, a process known as “training immunity”. This paper summarizes the anti-TB effect of BCG and focuses on its heterologous protection and related mechanism.

Curcumin inhibits oxidative stress in BCG-infected macrophages based on Nrf2 pathway / 中国免疫学杂志

Objective:To investigate the inhibitory effect of curcumin on oxidative stress in BCG-infected macrophages based on the Nrf2 pathway.Methods:THP-1-derived macrophages were infected.The experiment was divided into control group,BCG group,BCG+curcumin group and BCG+curcumin+ML385 group.Cellular ROS fluorescence intensity were observed under a fluores-cence microscope;Glutathione(GSH)levels were measured by Colorimetry;Western blot was used to detect the protein expressions of Nrf2,HO-1 and NQO1;MTT was used to detect the proliferation rate of macrophages.Results:BCG infection significantly enhanced ROS fluorescence intensity,reduced cell GSH content(P<0.01),inhibited protein expressions of Nrf2,HO-1 and NQO1,at the same time inhibited cell proliferation(P<0.01);curcumin significantly weakened ROS fluorescence intensity,increased GSH level(P<0.05),promoted Nrf2,HO-1 and NQO1 protein expressions and cell proliferation(P<0.01);Nrf2 inhibitor ML385 reversed the effect of curcumin.Conclusion:Curcumin can alleviate BCG-induced oxidative stress in macrophages by increasing the expression of Nrf2 and inducing the transcription of downstream antioxidant molecules.

Immunogenicity of BCG-CpG-DNA adjuvant rabies vaccine(MRC-5 cell)for human use in cynomolgus monkeys / 中国人兽共患病学报

To evaluate the immunogenicity of BCG-CpG-DNA-adjuvanted human rabies vaccine(MRC-5 cell)in cynomol-gus monkeys,we randomly divided monkeys into a control group,three-dose group,and four-dose group.The three-dose and four-dose groups were vaccinated with BCG-CpG-DNA-adjuvanted human rabies vaccine for human use at 0,7,and 21,or at 0,3,7,and 14 days,respectively.The control group was vaccinated with a commercially available domestic vaccine with a 2-1-1 protocol.Serum samples were collected from all monkeys before(0 day)and after immunization,on days 7,14,28,35,49,and 63.RFFIT and ELISPOT were used to detect anti-rabies virus neutralizing antibodies and cytokines(IFN-γ and IL-2).The anti-rabies virus neutralizing antibodies in all groups were negative before immunization.The three-dose and control groups showed an increasing trend from 7 to 28 days after primary immunization,and the highest level was reached on the 28th day;in contrast,the four-dose group showed a peak on the 14th day.On the 28th day,the neutralizing antibody levels in the control and three-dose groups were significantly higher than those in the four-dose group.On the 35th day after the initial immuniza-tion,the neutralizing antibodies in the three-dose group was significantly higher than those in the four-dose group.The levels of IL-2 and IFN-γ in peripheral blood lymphocytes in the three-dose and four-dose groups tended to increase from 7 to 14 days and peaked on the 14th day;the level of IFN-γ in the three-dose group was significantly higher than that in the control group on the 14th day.Otherwise,no significant differences in the levels of neutrali-zing antibodies and cytokines were observed among all groups at all other time points.Thus,BCG-CpG-DNA adjuvanted human rabies vaccine(MRC-5 cell)has excellent immunogenicity and application value for optimizing immunization procedures.

Sea-buckthorn slows down-regulation of CYP 2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway / 中国药理学通报

Aim To explore whether sea-buckthorn slows down-regulation of hepatic cytochrome P450 2C(CYP 2C)in mice with liver injury by BCG vaccine(BCG)-induced via PXR/NF-κB pathway.Methods The mouse model of liver injury was induced by a single tail vein injection of BCG 125 mg·kg-1 for hepatitis B research,and the mice were randomly di-vided into control group,BCG group,BCG+sea-buckthorn granules(SG)group(gavage 50,100,200 mg·kg-1,twice a day),BCG+PCN group(intraper-itoneal injection 100 mg·kg-1,once a day).The levels of serum transaminase and TNF-α and IL-1β in liver tissue were detected by ELISA.The nuclear pro-tein expression NF-κB p65 and the total protein expres-sion of pregnane X receptor(PXR),CYP2C in liver were detected by Western blot.Liver pathological changes were observed by HE staining.Results Sea-buckthorn inhibited overexpression of TNF-α,IL-1βand NF-κB p65,alleviated the down-regulation of CYP2C and PXR protein expression,and improved liv-er pathology and serum transaminase in a dose-depend-ent manner.After intervention with PCN,a mouse specific agonist of PXR,it was similar to the high dose group of SG.Conclusion Sea-buckthorn slows down-regulation of CYP2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway.

Coinfección por helmintos y Mycobacteriumtuberculosis

Introducción: Las infecciones por helmintos y Mycobacterium tuberculosis se superponen geográficamente, en particular en los países de ingresos económicos bajos y medianos, donde son altamente endémicas. En estos, la mayoría de las personas se infectan crónicamente por uno o ambos tipos de patógenos en etapas tempranas de sus vidas. Objetivo: Incursionar en los principales aspectos inmunológicos de la coinfección helmintos-M. tuberculosis y sus consecuencias para la progresión de la infección por M. tuberculosis y la vacunación contra la tuberculosis. Métodos: Revisión de artículos sobre inmunología, diagnóstico, tratamiento y control de las infecciones por helmintos y M. tuberculosis publicados entre 2010-2022 en las bases de datos PubMed, Medline y Google Scholar. Se consultaron, además, algunas monografías y artículos originales fechados con anterioridad. Análisis y síntesis de la información: Durante la infección crónica por helmintos, la modulación de las respuestas inmunitarias Th2 y Tregs por parte de esos parásitos podría inhibir las respuestas inmunitarias Th1 y Th17 contra la infección por M. tuberculosis y conducir a su progresión desde la fase latente, de escasa expresión clínica, hasta la fase activa de la tuberculosis. La modulación inmune de los helmintos podría dar lugar a una respuesta deficiente a la vacunación con BCG. Resultados epidemiológicos demuestran que la inmunomodulación podría revertirse mediante tratamientos antihelmínticos. Conclusiones: En la infección crónica por helmintos, es importante considerar que la modulación de sus respuestas inmunitarias activa circuitos inmunorreguladores complejos que pueden conducir a formas graves de la tuberculosis en el hospedero y a respuesta deficiente a la vacunación con BCG.

Introduction: Helminth and Mycobacterium tuberculosis infections overlap geographically, particularly in low- and middle-income countries, where they are highly endemic. There, most people are chronically infected by one or both types of pathogens early in their lives. Objective: To explore the main immunological aspects of helminth-M tuberculosis coinfection and its consequences for the progression of M. tuberculosis infection and vaccination against tuberculosis. Methods: A review of articles on immunology, diagnosis, treatment, and control of helminth and M. tuberculosis infections was conducted on those published between 2010-2022 in PubMed, Medline, and Google Scholar databases. In addition, some previously dated original monographs and articles were consulted. Analysis and synthesis of information: During chronic helminth infection, modulation of Th2 and Treg immune responses by these parasites could inhibit Th1 and Th17 immune responses against M. tuberculosis infection and lead to its progression from the latent phase, with little clinical expression, to the active phase of tuberculosis. Immune modulation of helminths could lead to poor response to BCG vaccination. Epidemiological results show that immunomodulation could be reversed by anthelmintic treatments. Conclusions: In chronic helminth infection, it is important to consider that the modulation of their immune responses activates complex immunoregulatory circuits that can lead to severe forms of tuberculosis in the host and poor response to BCG vaccination.

Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur

BACKGROUND The Bacille Calmette-Guérin (BCG) vaccine comprises a family of strains with variable protective efficacy against pulmonary tuberculosis (TB) and leprosy, partly due to genetic differences between strains. OBJECTIVES Previous data highlighting differences between the genomes and proteomic profiles of BCG strains Moreau and Pasteur led us to evaluate their behaviour in the macrophage microenvironment, capable of stimulating molecular responses that can impact the protective effect of the vaccine. METHODS Strain infectivity, viability, co-localisation with acidified vesicles, macrophage secretion of IL-1 and MCP-1 and lipid droplet biogenesis were evaluated after infection. FINDINGS We found that BCG Moreau is internalised more efficiently, with significantly better intracellular survival up to 96 h p.i., whereas more BCG Pasteur bacilli were found co-localised in acidified vesicles up to 6 h p.i. IL-1β and MCP-1 secretion and lipid droplet biogenesis by infected macrophages were more prominent in response to BCG Pasteur. MAIN CONCLUSION Overall, our results show that, compared to Pasteur, BCG Moreau has increased fitness and better endurance in the harsh intracellular environment, also regulating anti-microbial responses (lower IL-1b and MCP-1). These findings contribute to the understanding of the physiology of BCG Moreau and Pasteur in response to the intraphagosomal environment in a THP-1 macrophage model.

Does BCG Or MMR Or Routine Vaccination Coverage Protect Against COVID Infection And Mortality In India?

Background: The routine vaccinations and acquired immunity by other viral infections were believed to be acting as a protective factor against severe COVID-19 outbreaks in some countries. Objective: This study is overviewing the relationship of routine BCG, MMR vaccinations and reported MMR disease outbreak with reported COVID-19 infection across the Indian states. Methods: The data on vaccination coverage and respiratory disease infection was obtained from Univer-sal immunization program and Integrated disease surveillance project reports. Spearman rank correla-tion has been used to assess the relationship of routine vaccination and COVID-19 infection. Results: The result did not find any relationship of routine vaccination with BCG and MMR or exposure to MMR infection on COVID-19 infections in India. Conclusion: The exposure to BCG or MMR vaccination did not have a non-specific protection against COVID-19 infection. The results imply that a larger proportion of the Indian population is still vulnerable to COVID-19 infection.

Producción de vacunas en el antiguo Instituto Bacteriológico de Chile / Vaccine production at the ancient Bacteriological Institute of Chile

Se relata el nacimiento, auge y decadencia, de la producción de vacunas en el antiguo Instituto Bacteriológico de Chile, desde su fundación en 1929 hasta su fin en 1980, por boca de quien fuera por diecisiete años primero encargado de la fabricación de vacunas bacterianas y luego director de la institución. Las vicisitudes de la vacuna BCG, la introducción del toxoide tetánico, el fin de la vacuna antivariólica y el triunfo de vacuna antirrábica de Fuenzalida y Palacios, se narran a menudo con comentarios de quienes participaron en estos hechos.

The birth, rise and decline, of vaccine production at the Bacteriological Institute of Chile is recounted by mouth of who was for seventeen years first in charge of manufacturing and then director of the institution. The vicissitudes of the BCG vaccine, the introduction of tetanus toxoid, the end of smallpox vaccine, and the triumph of the rabies vaccine are often related with comments from those who participated in the events.