Table 1 Clinical trials of BCG as a mitigation factor against infectious diseases other than TB.
From: The double-sided effects of Mycobacterium Bovis bacillus Calmette–Guérin vaccine
Pathogens | ID | Possible mechanism | Phase | Country | Time | Enrollment | Subjects | Aims | Outcome measures |
|---|---|---|---|---|---|---|---|---|---|
Influenza virus | NCT02114255 | Trained immunity | II/III | Netherlands | May 2014–Sep. 2014 | 40 | Healthy adult (male) | To investigate whether prior BCG vaccination improves the efficacy of influenza vaccination in young and/or old healthy volunteers. | ✧ Thrombocyte function. ✧ Seroprotection (Influenza antibody titer ≥1:40 or ≥4-fold rise). ✧ Granzyme B, IFN-γ, IL-10, IL-17, and IL-22 by leukocytes ex vivo stimulated with inactivated/live influenza virus. ✧ TNF-α, IL-1β, IFN-γ, IL-10, IL-17, IL-22 by leukocytes ex vivo stimulated with different not-related stimuli. |
Hepatitis B | NCT02444611 | Trained immunity | NA | Australia | Mar. 2015–Jun. 2016 | 185 | Child | To investigate the effects of BCG and Hepatitis B vaccine, given at birth, on the neonatal immune responses against non-specific antigens. | ✧ Cytokine concentrations in response to in vitro stimulation with a range of homologous or heterologous antigens (IL-1α, IL-1β, MCP-1, MIP-1α, MIP-1β, IFN-γ, IL-10, MIF, MIG, TNF-α). |
HIV | NCT00331474 | Immune activation | I/II | South Africa | May 2006–Aug. 2009 | 180 | Infant | To investigate whether BCG can trigger immune responses against HIV, and whether BCG can regulate the spreading of HIV and early progression to AIDS in babies borned from HIV-positive mothers. | ✧ BCG-induced cellular immune responses. ✧ Serum antibody responses. ✧ BCG scarring and TB incidence. |
NCT02062580 | Immune activation | II | South Africa | Jun. 2010–Apr. 2012 | 149 | Infant | To investigate whether routine BCG immunization of neonates contributes to generalized immune activation in HIV-exposed infants and increased rates of disease progression in HIV-infected infants. | ✧ Percentage of all CD4+ T cells expressing HLA-DR. ✧ Percent of CD4+ T cells expressing Ki-67 after stimulation in vitro with BCG. | |
NCT02606526 | Trained immunity | III | Uganda | Jul. 2016– | 2200 | Infant | To investigate whether BCG vaccination at birth, in a high-risk HIV-exposed can protect infants against serious infections other than TB. | ✧ Proportion of infants with severe illness. ✧ Production of TNF-α, IL-1β, IL-6 and IFN-γ in response to mycobacterial and non-mycobacterial antigens. ✧ Adverse events and infant death. | |
Malarial parasites | NCT00126217 | Trained immunity | IV | Guinea | Jul. 2002–Sep. 2006 | 2871 | Child | To investigate whether BCG boosting or no boosting have has an effect on the prevalence of malaria parasitaemia. | ✧ Adverse effects. ✧ Mortality till 5 years of age and malaria morbidity/parasitaemia within 12 months after intervention. ✧ Antibody and cellular immune responses 18 months after intervention. |
NCT00131794 | Trained immunity | III | Guinea | Jan. 2003–Dec. 2003 | 1200 | Child | Effect of BCG vaccine on morbidity caused by malaria infection. | ✧ Incidence of clinical malaria. ✧ Prevalence of malaria parasitemia. | |
NCT02692963 | Trained immunity | II | Netherlands | Apr. 2016–Feb. 2017 | 20 | Healthy adult | To investigate whether BCG vaccination can offer protection against malaria in the Controlled Human Malaria Infection (CHMI) model. | ✧ Frequency and magnitude of adverse events. ✧ Time to blood stage parasitemia detectable by qPCR. ✧ Changes in cellular (innate and adaptive) immune responses. ✧ Changes in plasma cytokine levels. | |
Bordetella pertussis | NCT02771782 | Trained immunity | IV | Netherlands | Jan. 2015–Jul. 2016 | 75 | Healthy adult (female) | To investigate whether BCG vaccination modulates an immune response against non-vaccine target antigens. | ✧ Antibody titers. ✧ PBMC cytokine response to homologous or heterologous antigens (IL-6, TNF-α, IL-1β, IL-10, IL-17, IL-22, IFN-γ). |
Corynebacterium diphtheria | NCT02771782 | Trained immunity | IV | Netherlands | Jan. 2015–Jul. 2016 | 75 | Healthy adult (female) | To investigate whether BCG vaccination modulates an immune response against non-vaccine target antigens. | ✧ Antibody titers. ✧ T-cell response and B-cell phenotype analysis. ✧ PBMC cytokine response to homologous or heterologous antigens (IL-6, TNF-α, IL-1β, IL-10, IL-17, IL-22, IFN-γ). |
