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Vaccines
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Adjuvants and Antigen Delivery Systems for Tuberculosis Subunit Vaccines
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Adjuvants and Antigen Delivery Systems for Tuberculosis Subunit Vaccines

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccine Adjuvants".

Deadline for manuscript submissions: closed (10 May 2021) | Viewed by 10002

Special Issue Editor

Prof. Dr. Abu Salim Mustafa

E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait
Interests: tuberculosis; vaccines; immunodiagnosis; immuno-pathogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The only licensed vaccine against tuberculosis is BCG. However, BCG has failed to provide consistent protection against tuberculosis, specially pulmonary disease in adults. The research towards development of new vaccines against TB includes the use of M. tuberculosis antigens as subunit vaccines. Such vaccines may be used either alone or in prime-boost model in BCG-vaccinated people. However, the antigens for subunit vaccines require adjuvants and/or delivery systems to induce appropriate and protective immune responses.  This special issue will focus on the use of different adjuvants and delivery systems, e.g. chemical adjuvants, liposomes,  nanoparticles, naked DNA, and viral and bacterial vectors, etc. in inducing the protective immune responses after immunization with subunit vaccines. The issue will include manuscripts related to the research in animal models and clinical trials in humans. 

Prof. Dr. Abu Mustafa
Guest Editor

Keywords

  • Tuberculosis
  • Subunit Vaccines
  • Adjuvants
  • Delivery systems
  • Liposomes
  • Nanoparticles
  • Bacterial vectors
  • Viral vectors
  • Plasmid (naked) DNA
  • Edible-based strategies

Published Papers (4 papers)

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Research

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14 pages, 3983 KiB  
Article
Decrease of IL-5 Production by Naive T Cells Cocultured with IL-18-Producing BCG-Pulsed Dendritic Cells from Patients Allergic to House Dust Mite
by Magdalena Kowalewicz-Kulbat, Piotr Szpakowski, Krzysztof T. Krawczyk, Marek L. Kowalski, Slawomir Kosinski, Franck Biet, Wieslawa Rudnicka and Camille Locht
Vaccines 2021, 9(3), 277; https://doi.org/10.3390/vaccines9030277 - 18 Mar 2021
Cited by 4 | Viewed by 2052
Abstract
The only currently available anti-tuberculosis vaccine, Bacillus Calmette–Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to [...] Read more.
The only currently available anti-tuberculosis vaccine, Bacillus Calmette–Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to reduce IL-5 production and bronchoalveolar eosinophilia in mice. However, their ability to decrease the immune polarization of human Th2 cells is not known. Here, we show that BCG and recombinant BCG producing human IL-18 (rBCG-hIL-18) induced the maturation of Der p 1-stimulated monocyte-derived dendritic cells (MD-DCs) from healthy controls and from patients allergic to house dust mites. After incubation with mycobacteria and Der p 1, MD-DCs produced significantly more IL-23 and IP-10 but had no effect on IL-12p70 or IL-10 production compared to Der p 1-pulsed MD-DCs in the absence of mycobacteria. In the presence of Der p 1, BCG- and rBCG-hIL-18-pulsed MD-DCs cocultured with naive, but not with memory T cells from allergic patients, resulted in a decrease in IL-5 production compared to non-pulsed MD-DCs cultured in the presence of Der p 1. BCG, and especially rBCG-hIL-18, may thus be potential therapeutic tools to reduce exacerbated Th2 responses in patients with allergic asthma. Full article
(This article belongs to the Special Issue Adjuvants and Antigen Delivery Systems for Tuberculosis Subunit Vaccines)
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9 pages, 386 KiB  
Article
The Spectrum of Bacille Calmette–Guérin Diseases in Children—A Decade of Data from Neonatal Vaccination Settings
by Noora Al Busaidi, Prakash KP, Amina Al-Jardani, Nashat Al-Sukaiti, Salem Al Tamemi, Bader Al-Rawahi, Zaid Al Hinai, Fatma Alyaquobi, Seif Al-Abri and Amal Al-Maani
Vaccines 2021, 9(2), 150; https://doi.org/10.3390/vaccines9020150 - 13 Feb 2021
Cited by 1 | Viewed by 1776
Abstract
In this paper, we present a multicentre record-based descriptive study used to estimate the incidence and characterize the spectrum of confirmed bacille Calmette–Guérin (BCG) vaccine-related disease among children in Oman. This study included all children (age ≤ 14 years) who had culture and/or [...] Read more.
In this paper, we present a multicentre record-based descriptive study used to estimate the incidence and characterize the spectrum of confirmed bacille Calmette–Guérin (BCG) vaccine-related disease among children in Oman. This study included all children (age ≤ 14 years) who had culture and/or polymerase chain reaction (PCR)-confirmed BCG disease from January 2006 to December 2018, as identified from Central Public Health Laboratory data and International Classification of Diseases coding of an electronic patient information system. In total, 88 children confirmed to have BCG disease were included in the study, making an average incidence of 9.2 cases per 100,000 vaccinated neonates. The males comprised 65.9%, Omanis 93.2%, and the median age of presentation was 4 months in children with BCG disease. The most common type of disease was BCG abscesses (72.4%). Children with immunodeficiency and those presenting within 6 months were found to have a more severe and disseminated disease. In total, 28 children had immunodeficiency. The age of presentation and type of BCG disease was significantly associated with immunodeficiency status. The majority of cases required therapy (both medical and surgical) and recovered well. The incidence of laboratory-confirmed BCG vaccine-related disease was low in Oman supporting continuing the use of the BCG vaccination practice at birth. Full article
(This article belongs to the Special Issue Adjuvants and Antigen Delivery Systems for Tuberculosis Subunit Vaccines)
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14 pages, 2418 KiB  
Article
Id3 and Bcl6 Promote the Development of Long-Term Immune Memory Induced by Tuberculosis Subunit Vaccine
by Jiangyuan Han, Yanlin Ma, Lan Ma, Daquan Tan, Hongxia Niu, Chunxiang Bai, Youjun Mi, Tao Xie, Wei Lv, Juan Wang and Bingdong Zhu
Vaccines 2021, 9(2), 126; https://doi.org/10.3390/vaccines9020126 - 05 Feb 2021
Cited by 11 | Viewed by 2187
Abstract
Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging [...] Read more.
Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging the immune memory induced by a tuberculosis (TB) subunit vaccine. To address this research gap, mice were treated with the Mycobacterium tuberculosis (M. tuberculosis) subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64<190–198>-Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1 at 0, 2, and 4 weeks, respectively. Immune responses induced by the vaccine were examined at 25 weeks after last immunization. The results showed that adeno-associated virus-mediated IL-7 allowed the TB subunit vaccine to induce the formation of long-lived memory T cells. Meanwhile, IL-7 increased the expression of Id3, Bcl6, and bach2—the three key transcription factors for the generation of long-lived memory T cells. The adjuvant effects of transcriptional factors, together with TB fusion protein MH/LT70 vaccination, showed that both Bcl6 and Id3 increased the production of antigen-specific antibodies and long-lived memory T cells, characterized by high proliferative potential of antigen-specific CD4+ and CD8+ T cells, and IFN-γ secretion in CD4+ and CD8+ T cells, respectively, after re-exposure to the same antigen. Overall, our study suggests that IL-7 and transcriptional factors Id3 and Bcl6 help the TB subunit vaccine to induce long-term immune memory, which contributes to providing immune protection against M. tuberculosis infection. Full article
(This article belongs to the Special Issue Adjuvants and Antigen Delivery Systems for Tuberculosis Subunit Vaccines)
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Review

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17 pages, 688 KiB  
Review
Immunological Characterization of Proteins Expressed by Genes Located in Mycobacterium tuberculosis-Specific Genomic Regions Encoding the ESAT6-like Proteins
by Abu Salim Mustafa
Vaccines 2021, 9(1), 27; https://doi.org/10.3390/vaccines9010027 - 07 Jan 2021
Cited by 9 | Viewed by 3320
Abstract
The 6 kDa early secreted antigen target (ESAT6) is a low molecular weight and highly immunogenic protein of Mycobacterium tuberculosis with relevance in the diagnosis of tuberculosis and subunit vaccine development. The gene encoding the ESAT6 protein is located in the M. tuberculosis [...] Read more.
The 6 kDa early secreted antigen target (ESAT6) is a low molecular weight and highly immunogenic protein of Mycobacterium tuberculosis with relevance in the diagnosis of tuberculosis and subunit vaccine development. The gene encoding the ESAT6 protein is located in the M. tuberculosis-specific genomic region known as the region of difference (RD)1. There are 11 M. tuberculosis-specific RDs absent in all of the vaccine strains of BCG, and three of them (RD1, RD7, and RD9) encode immunodominant proteins. Each of these RDs has genes for a pair of ESAT6-like proteins. The immunological characterizations of all the possible proteins encoded by genes in RD1, RD7 and RD9 have shown that, besides ESAT-6 like proteins, several other proteins are major antigens useful for the development of subunit vaccines to substitute or supplement BCG. Furthermore, some of these proteins may replace the purified protein derivative of M. tuberculosis in the specific diagnosis of tuberculosis by using interferon-gamma release assays and/or tuberculin-type skin tests. At least three subunit vaccine candidates containing ESAT6-like proteins as antigen components of multimeric proteins have shown efficacy in phase 1 and phase II clinical trials in humans. Full article
(This article belongs to the Special Issue Adjuvants and Antigen Delivery Systems for Tuberculosis Subunit Vaccines)
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