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Approaches towards the development of a vaccine against tuberculosis: recombinant BCG and DNA vaccine

Mohd Nor N, Musa M

Tuberculosis (Edinb), 2004;84(1-2):102-9.
PMID: 14670351 DOI: 10.1016/j.tube.2003.08.011

The last few years have witnessed intense research on vaccine development against tuberculosis. This has been driven by the upsurge of tuberculosis cases globally, especially those caused by multi-drug-resistant Mycobacterium tuberculosis strains. Various vaccine strategies are currently being developed which can be broadly divided into the so-called living and non-living vaccines. Examples are attenuated members of the M. tuberculosis complex, recombinant mycobacteria, subunit proteins and DNA vaccines. Given current developments, we anticipate that recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M. tuberculosis may need to be cloned in a vaccine construct for the desired efficacy to be achieved. The technique of assembly polymerase chain reaction could facilitate such a cloning procedure.
Fulltext Immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum on LPS- or LPS+IFN-γ-stimulated J774A.1 cells

Mohamad D, Suppian R, Mohd Nor N

Hum Vaccin Immunother, 2014;10(7):1880-6.
PMID: 25424796 DOI: 10.4161/hv.28695

Macrophage phagocytosis is the first line of defense of the innate immune system against malaria parasite infection. This study evaluated the immunomodulatory effects of BCG and recombinant BCG (rBCG) strains expressing the C-terminus of the merozoite surface protein-1 (MSP-1C) of Plasmodium falciparum on mouse macrophage cell line J774A.1 in the presence or absence of lipopolysaccharide (LPS) or LPS + IFN-γ. The rBCG strain significantly enhanced phagocytic activity, production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nitric oxide (NO), and inducible nitric oxide synthase (iNOS) as compared with parental BCG strain, and these activities increased in the presence of LPS and LPS+IFN-γ. Furthermore, the rBCG strain also significantly reduced the macrophage viability as well as the rBCG growth suggesting the involvement of macrophage apoptosis. Taken together, these data indicate that the rBCG strain has an immunomodulatory effect on macrophages, thus strengthen the rational use of rBCG to control malaria infection.
Understanding the genetic history of Malay populations in Peninsular Malaysia via KIR genes diversity

Hanis Zainal Abidin NW, Mohd Nor N, Sundararajulu P, Zafarina Z

Am J Hum Biol, 2020 Dec 01.
PMID: 33289243 DOI: 10.1002/ajhb.23545

OBJECTIVES: Killer cell immunoglobulin-like receptor (KIR) genes with high polymorphism at genotypic levels are important in providing immune defense and have been expanded towards human population genetics. The aim of this study is to provide supporting information from this new biomarker to strengthen the comprehension of genetic history of the complex Malay population.
METHODS: KIR genotyping for 213 unadmixed Malay individuals from six subethnic groups (Acheh, Bugis, Champa, Mandailing, Minang and Kedah) was carried out using PCR-SSP (sequence specific primers) method in 16 independent reactions.
RESULTS: The most frequent KIR genotype observed is AA1, followed by AB4 and AB5. Five genotypes; AA1, AB4, AB5, AB7 and AB8 were shared among all Malay subethnic groups. The highest frequency of KIR haplotype A was observed in Minang Malays, whereas Acheh and Kedah Malays carry a balanced distribution of A and B KIR haplotypes. PCA for the KIR genes clearly illustrated six ethnogeographical population clusters; Africans, Amerindian, Northeast Asian, South Asian, Oceania and Southeast Asian populations. All six Malay subethnic groups fell within the Southeast Asian cluster.
CONCLUSIONS: The complex array of KIR genotypes observed in the Malays indicates their historical interactions with various populations, especially with the Chinese, Indians and Orang Asli. This study has demonstrated the potential of KIR genes as a genetic marker for deducing population structure and genetic relationship between populations.
Application of Reverse Vaccinology and Immunoinformatic Strategies for the Identification of Vaccine Candidates Against Shigella flexneri

Leow CY, Chuah C, Abdul Majeed AB, Mohd Nor N, Leow CH

Methods Mol Biol, 2022;2414:17-35.
PMID: 34784029 DOI: 10.1007/978-1-0716-1900-1_2

Reverse vaccinology (RV) was first introduced by Rappuoli for the development of an effective vaccine against serogroup B Neisseria meningitidis (MenB). With the advances in next generation sequencing technologies, the amount of genomic data has risen exponentially. Since then, the RV approach has widely been used to discover potential vaccine protein targets by screening whole genome sequences of pathogens using a combination of sophisticated computational algorithms and bioinformatic tools. In contrast to conventional vaccine development strategies, RV offers a novel method to facilitate rapid vaccine design and reduces reliance on the traditional, relatively tedious, and labor-intensive approach based on Pasteur"s principles of isolating, inactivating, and injecting the causative agent of an infectious disease. Advances in biocomputational techniques have remarkably increased the significance for the rapid identification of the proteins that are secreted or expressed on the surface of pathogens. Immunogenic proteins which are able to induce the immune response in the hosts can be predicted based on the immune epitopes present within the protein sequence. To date, RV has successfully been applied to develop vaccines against a variety of infectious pathogens. In this chapter, we apply a pipeline of bioinformatic programs for identification of Shigella flexneri potential vaccine candidates as an illustration immunoinformatic tools available for RV.
Fulltext Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis

Alvarez N, Infante JF, Borrero R, Mata D, Payan JB, Hossain MM, et al.

Malays J Med Sci, 2014 May;21(3):31-7.
PMID: 25246833 MyJurnal

Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis.
Parasitic infections in Malaysian aborigines with pulmonary tuberculosis: a comparative cross-sectional study

Wong WK, Mohd-Nor N, Noordin R, Foo PC, Mohamed Z, Haq JA, et al.

Parasitol Res, 2019 Sep;118(9):2635-2642.
PMID: 31363922 DOI: 10.1007/s00436-019-06406-7

The geographical distribution of tuberculosis (TB) overlaps with various parasitic infections. Uncovering the characteristics of coinfecting parasites that potentially affect the host susceptibility to TB is pertinent as it may provide input to current TB therapeutic and prophylactic measures. The present study was aimed at examining the types of parasitic infections in TB patients and healthy TB contacts (HC) in Orang Asli, Malaysian aborigines, who dwelled in the co-endemic areas. Stool and serum samples were collected from Orang Asli who fulfilled the selection criteria and provided written informed consents. Selected parasitic infections in the two study groups were determined by stool examination and commercial serum antibody immunoassays. The prevalence of parasitic infections in TB and HC participants were 100% (n = 82) and 94.6% (n = 55) respectively. The parasitic infections comprised toxocariasis, trichuriasis, amoebiasis, toxoplasmosis, hookworm infection, ascariasis, strongyloidiasis, and brugian filariasis, in decreasing order of prevalence. Overall, helminth or protozoa infection did not show any significant association with the study groups. However, when the species of the parasite was considered, individuals exposed to trichuriasis and toxoplasmosis showed significant odds reduction (odds ratio (OR) 0.338; 95% confidence interval (CI) 0.166, 0.688) and odds increment (OR 2.193; 95% CI 1.051, 4.576) to have active pulmonary TB, respectively. In conclusion, trichuriasis and toxoplasmosis may have distinct negative and positive associations respectively with the increase of host susceptibility to TB.
Fulltext Draft Genome Sequences of Local Clinical Isolates of Drug-Resistant and Drug-Sensitive Mycobacterium tuberculosis

Zainal Abidin N, Noorizhab MNF, Teh LK, Lim WF, Mohd Noordin N, Aziz ZA, et al.

Microbiol Resour Announc, 2021 Jun 24;10(25):e0035221.
PMID: 34165334 DOI: 10.1128/MRA.00352-21

In the battle against tuberculosis (TB), plasticity of the Mycobacterium tuberculosis genome is believed to contribute to the pathogen's virulence and drug resistance. Here, we report 10 draft genome sequences of clinical M. tuberculosis isolated in Malaysia as the basis for understanding the genome plasticity of the M. tuberculosis isolates.