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Fulltext Measles infection causing Bacillus Calmette-Guérin reactivation: a case report

Muthuvelu S, Lim KS, Huang LY, Chin ST, Mohan A

BMC Pediatr, 2019 07 24;19(1):251.
PMID: 31340782 DOI: 10.1186/s12887-019-1635-z

BACKGROUND: Reactivation of the Bacillus Calmette-Guérin (BCG), manifesting as erythema, induration, ulceration or crust formation at a previous BCG inoculation site, is a common and highly specific feature of Kawasaki disease (KD). We report the unusual finding of BCG reactivation in an infant with laboratory-confirmed measles.
CASE PRESENTATION: A previously healthy 7-month old infant presented initially with fever, cough and coryza, and subsequently developed Koplik's spots followed by a typical morbilliform skin rash. There was significant contact history with a household relative who had recently been diagnosed with measles. On examination, a 2.5 cm area of erythema and induration was seen at the previous BCG inoculation site, in addition to the widespread maculopapular rash. No other clinical features of KD were present. Measles virus was isolated from the throat swab and measles antibodies (IgM) were present in the serum. The patient recovered completely with oral vitamin A and supportive therapy, and had normal echocardiography examination on follow up.
CONCLUSIONS: This case report highlights the rare finding of BCG reactivation in a child with confirmed measles infection, and suggests that this clinical manifestation may occasionally occur in children with infections or conditions other than KD.

Matched MeSH terms: BCG Vaccine/immunology*
Fulltext Vaccines for TB: Lessons from the Past Translating into Future Potentials

Tye GJ, Lew MH, Choong YS, Lim TS, Sarmiento ME, Acosta A, et al.

J Immunol Res, 2015;2015:916780.
PMID: 26146643 DOI: 10.1155/2015/916780

Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB.

Matched MeSH terms: BCG Vaccine/immunology
Fulltext Risk of tuberculosis to healthcare workers

Liam CK

Med J Malaysia, 2001 Mar;56(1):107-11; quiz 112.
PMID: 11503290
Matched MeSH terms: BCG Vaccine/immunology
Fulltext Protective effect of a lipid-based preparation from Mycobacterium smegmatis in a murine model of progressive pulmonary tuberculosis

García Mde L, Borrero R, Lanio ME, Tirado Y, Alvarez N, Puig A, et al.

Biomed Res Int, 2014;2014:273129.
PMID: 25548767 DOI: 10.1155/2014/273129

A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.

Matched MeSH terms: BCG Vaccine/immunology
Immunogenicity of a recombinant Mycobacterium bovis bacille Calmette-Guèrin expressing malarial and tuberculosis epitopes

Rapeah S, Norazmi MN

Vaccine, 2006 Apr 24;24(17):3646-53.
PMID: 16494975 DOI: 10.1016/j.vaccine.2006.01.053

Recombinant Mycobacterium bovis bacille Calmette-Guèrin (rBCG) expressing the malarial epitopes F2R(II)EBA and (NANP)3 as well as two T cell epitopes of the M. tuberculosis ESAT-6 antigen, generated in favour of mycobacterium codon usage elicited specific immune response against these epitopes. Immunised Balb/c mice demonstrated an increase in almost all of the IgG subclasses against both malarial epitopes and enhanced splenocyte proliferative response against the malarial epitopes as well as selected peptides of ESAT-6. Furthermore, flow cytometric analyses showed elevated numbers of CD4+ lymphocytes expressing IFN-gamma and IL-2 against the ESAT-6 peptides, suggesting a specific Th1-mediated response. This study demonstrated that expressing malarial and TB epitopes in a single rBCG construct induced appropriate humoral and cellular immune response against immunogenic epitopes from both organisms.

Matched MeSH terms: BCG Vaccine/immunology*
Fulltext The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

Abbas MA, Suppian R

J Infect Dev Ctries, 2019 11 30;13(11):1057-1061.
PMID: 32087079 DOI: 10.3855/jidc.11331

INTRODUCTION: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4).
METHODOLOGY: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively.
RESULTS: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242.
CONCLUSIONS: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

Matched MeSH terms: BCG Vaccine/immunology*
Fulltext Immunogenicity of recombinant Mycobacterium bovis bacille Calmette-Guèrin clones expressing T and B cell epitopes of Mycobacterium tuberculosis antigens

Mohamud R, Azlan M, Yero D, Alvarez N, Sarmiento ME, Acosta A, et al.

BMC Immunol, 2013;14 Suppl 1:S5.
PMID: 23458635 DOI: 10.1186/1471-2172-14-S1-S5

Recombinant Mycobacterium bovis bacille Calmette-Guèrin (rBCG) expressing three T cell epitopes of Mycobacterium tuberculosis (MTB) Ag85B antigen (P1, P2, P3) fused to the Mtb8.4 protein (rBCG018) or a combination of these antigens fused to B cell epitopes from ESAT-6, CFP-10 and MTP40 proteins (rBCG032) were used to immunize Balb/c mice. Total IgG responses were determined against Mtb8.4 antigen and ESAT-6 and CFP-10 B cell epitopes after immunization with rBCG032. Mice immunized with rBCG032 showed a significant increase in IgG1 and IgG2a antibodies against ESAT-6 and MTP40 (P1) B cell epitopes and IgG3 against both P1 and P2 B cell epitopes of MPT40. Splenocytes from mice immunized with rBCG018 proliferated against Ag85B P2 and P3 T cell epitopes and Mtb8.4 protein whereas those from mice-immunized with rBCG032 responded against all Ag85B epitopes and the ESAT-6 B cell epitope. CD4⁺ and CD8⁺ lymphocytes from mice immunized with rBCG018 produced primarily Th1 type cytokines in response to the T cell epitopes. Similar pattern of recognition against the T cell epitopes were obtained with rBCG032 with the additional recognition of ESAT-6, CFP-10 and one of the MTP40 B cell epitopes with the same pattern of cytokines. This study demonstrates that rBCG constructs expressing either T or T and B cell epitopes of MTB induced appropriate immunogenicity against MTB.

Matched MeSH terms: BCG Vaccine/immunology*
Fulltext Immunogenicity of recombinant BCG-based vaccine expressing the 22 kDa of serine repeat antigen (SE22) of Plasmodium falciparum

Teo WH, Nurul AA, Norazmi MN

Trop Biomed, 2012 Jun;29(2):239-53.
PMID: 22735846 MyJurnal

The Plasmodium falciparum serine repeat antigen (SERA) is one of the promising blood-stage malarial vaccine candidates. In this study, recombinant Mycobacterium bovis bacille Calmette-Guerin (rBCG) expressing the 22 kDa protein (SE22) from the 47 kDa Nterminal domain of serine repeat antigen (SERA), generated in favour of mycobacterium codon usage, elicited specific immune response in BALB/c mice with a mixed Th1/Th2 profile. Immunized sera containing high levels of specific IgG1 and IgG2a against the epitope (as determined by ELISA) were reactive with fixed P. falciparum merozoites as demonstrated by indirect immunofluorescence assay (IFA). Furthermore, the lymphocyte proliferative response to SE22 antigen from rBCG-immunized mice was higher than that of controls. The expression of intracellular cytokines (IL-2, IL-4 and IFNγ) in CD4+- and CD8+-cells was also enhanced following in-vitro stimulation with SE22. These findings indicate that a rBCG-based vaccine candidate expressing a blood-stage antigen of P. falciparum could enhance both humoral and cellular immune responses, thus paving the way for the rational use of rBCG as a vaccine candidate against malaria.

Matched MeSH terms: BCG Vaccine/immunology*