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Vaccines
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Vaccines Targeting Bacterial Infections
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Vaccines Targeting Bacterial Infections

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Infectious Diseases".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 9599

Special Issue Editor

Dr. Stephanie Ascough

E-Mail Website
Guest Editor
Department of Infectious Disease, Imperial College, London, UK
Interests: adaptive immunity; anthrax; b cells; bacteria; influenza; plague; respiratory; RSV; T cells; virus

Special Issue Information

Dear Colleagues,

Vaccines against bacterial pathogens are recognised as incredibly effective tools, capable of preventing morbidity and mortality caused by a wide variety of pathogens every year. However, despite the global success of vaccines against Mycobacterium tuberculosis, Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, Corynebacterium diphtheriae and Bordetella pertussis, these bacterial pathogens still evade eradication. There is therefore an urgent unmet need for improved vaccines to combat these and other circulating and emerging bacterial infections. This need has become especially pressing in the face of growing antimicrobial resistance (AMR), which is steadily reducing the effectiveness of therapeutic agents previously relied upon to treat bacterial infections. In addition, as the population of older adults continues to grow, close attention should be paid to age-related changes which affect the innate and adaptive immune systems, modulating older individuals’ capacity to mount an effective immune response. This ‘inflammaging’ and immunosenescence may mandate different vaccine requirements at different stages of life—a factor which has often been overlooked in bacterial vaccine design.

In recent years it has become evident that a major hurdle to vaccine development is the lack of knowledge regarding antigen-specific immunity for a variety of bacterial infections. This Special Issue of Vaccines focuses on research that aims to understand how adaptive and innate immunity against bacterial pathogens can be harnessed to develop new antigens, adjuvants, and vaccine delivery systems which will provide life-long protection.

Dr. Stephanie Ascough
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vaccine development
  • bacterial infection
  • immunity
  • host response
  • pathogens
  • immunogens
  • antigens
  • adjuvants
  • memory
  • vaccine efficacy
  • antimicrobial resistance
  • inflammaging
  • immunosenescence
  • toxoids
  • subunit vaccines
  • killed whole-cell vaccines
  • live attenuated vaccines
  • next-generation vaccines

Published Papers (4 papers)

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Research

17 pages, 1801 KiB  
Article
An RNA-Based Vaccine Platform for Use against Mycobacterium tuberculosis
by Sasha E. Larsen, Jesse H. Erasmus, Valerie A. Reese, Tiffany Pecor, Jacob Archer, Amit Kandahar, Fan-Chi Hsu, Katrina Nicholes, Steven G. Reed, Susan L. Baldwin and Rhea N. Coler
Vaccines 2023, 11(1), 130; https://doi.org/10.3390/vaccines11010130 - 05 Jan 2023
Cited by 15 | Viewed by 3264
Abstract
Mycobacterium tuberculosis (M.tb), a bacterial pathogen that causes tuberculosis disease (TB), exerts an extensive burden on global health. The complex nature of M.tb, coupled with different TB disease stages, has made identifying immune correlates of protection challenging and subsequently slowing vaccine candidate progress. [...] Read more.
Mycobacterium tuberculosis (M.tb), a bacterial pathogen that causes tuberculosis disease (TB), exerts an extensive burden on global health. The complex nature of M.tb, coupled with different TB disease stages, has made identifying immune correlates of protection challenging and subsequently slowing vaccine candidate progress. In this work, we leveraged two delivery platforms as prophylactic vaccines to assess immunity and subsequent efficacy against low-dose and ultra-low-dose aerosol challenges with M.tb H37Rv in C57BL/6 mice. Our second-generation TB vaccine candidate ID91 was produced as a fusion protein formulated with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion) or as a novel replicating-RNA (repRNA) formulated in a nanostructured lipid carrier. Protein subunit- and RNA-based vaccines preferentially elicit cellular immune responses to different ID91 epitopes. In a single prophylactic immunization screen, both platforms reduced pulmonary bacterial burden compared to the controls. Excitingly, in prime-boost strategies, the groups that received heterologous RNA-prime, protein-boost or combination immunizations demonstrated the greatest reduction in bacterial burden and a unique humoral and cellular immune response profile. These data are the first to report that repRNA platforms are a viable system for TB vaccines and should be pursued with high-priority M.tb antigens containing CD4+ and CD8+ T-cell epitopes. Full article
(This article belongs to the Special Issue Vaccines Targeting Bacterial Infections)
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12 pages, 12886 KiB  
Article
The Subunit AEC/BC02 Vaccine Combined with Antibiotics Provides Protection in Mycobacterium tuberculosis-Infected Guinea Pigs
by Xiaonan Guo, Jinbiao Lu, Junli Li, Weixin Du, Xiaobing Shen, Cheng Su, Yongge Wu, Aihua Zhao and Miao Xu
Vaccines 2022, 10(12), 2164; https://doi.org/10.3390/vaccines10122164 - 16 Dec 2022
Cited by 4 | Viewed by 1424
Abstract
A latent tuberculosis infection (LTBI) is a major source of active tuberculosis, and addressing an LTBI is crucial for the elimination of tuberculosis. The treatment of tuberculosis often requires a 6-month course of multidrug therapy, and for drug-resistant tuberculosis, a longer course of [...] Read more.
A latent tuberculosis infection (LTBI) is a major source of active tuberculosis, and addressing an LTBI is crucial for the elimination of tuberculosis. The treatment of tuberculosis often requires a 6-month course of multidrug therapy, and for drug-resistant tuberculosis, a longer course of multidrug therapy is needed, which has many drawbacks. At present, vaccines are proposed as an adjunct to chemotherapy to protect populations with an LTBI and delay its recurrence. In this study, we analyzed the protective effect of a novel subunit vaccine, AEC/BC02, in a guinea pig latent infection model. Through the optimization of different chemotherapy durations and immunization times, it was found that 4 weeks of administration of isoniazid–rifampin tablets combined with three or six injections of the vaccine could significantly reduce the gross pathological score and bacterial load in organs and improve the pathological lesions. This treatment regimen had a better protective effect than the other administration methods. Furthermore, no drug resistance of Mycobacterium tuberculosis was detected after 2 or 4 weeks of administration of the isoniazid–rifampin tablets, indicating a low risk of developing drug-resistant bacteria during short-term chemotherapy. The above results provided the foundation for an AEC/BC02 clinical protocol. Full article
(This article belongs to the Special Issue Vaccines Targeting Bacterial Infections)
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20 pages, 3703 KiB  
Article
Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei
by Muhammad Irfan, Saifullah Khan, Alaa R. Hameed, Alhanouf I. Al-Harbi, Syed Ainul Abideen, Saba Ismail, Asad Ullah, Sumra Wajid Abbasi and Sajjad Ahmad
Vaccines 2022, 10(10), 1580; https://doi.org/10.3390/vaccines10101580 - 21 Sep 2022
Cited by 4 | Viewed by 1893
Abstract
The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted in high mortality as well as high health care costs. Burkholderia mallei is one of the etiological agents of health care-associated infections. As no licensed [...] Read more.
The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted in high mortality as well as high health care costs. Burkholderia mallei is one of the etiological agents of health care-associated infections. As no licensed vaccine is available against the pathogen herein, using reverse vaccinology, bioinformatics, and immunoinformatics approaches, a multi-epitope-based vaccine against B. mallei was designed. In completely sequenced proteomes of B. mallei, 18,405 core, 3671 non-redundant, and 14,734 redundant proteins were predicted. Among the 3671 non-redundant proteins, 3 proteins were predicted in the extracellular matrix, 11 were predicted as outer membrane proteins, and 11 proteins were predicted in the periplasmic membrane. Only two proteins, type VI secretion system tube protein (Hcp) and type IV pilus secretin proteins, were selected for epitope prediction. Six epitopes, EAMPERMPAA, RSSPPAAGA, DNRPISINL, RQRFDAHAR, AERERQRFDA, and HARAAQLEPL, were shortlisted for multi-epitopes vaccine design. The predicted epitopes were linked to each other via a specific GPGPG linker and the epitopes peptide was then linked to an adjuvant molecule through an EAAAK linker to make the designed vaccine more immunologically potent. The designed vaccine was also found to have favorable physicochemical properties with a low molecular weight and fewer transmembrane helices. Molecular docking studies revealed vaccine construct stable binding with MHC-I, MHC-II, and TLR-4 with energy scores of −944.1 kcal/mol, −975.5 kcal/mol, and −1067.3 kcal/mol, respectively. Molecular dynamic simulation assay noticed stable dynamics of the docked vaccine-receptors complexes and no drastic changes were observed. Binding free energies estimation revealed a net value of −283.74 kcal/mol for the vaccine-MHC-I complex, −296.88 kcal/mol for the vaccine-MHC-II complex, and −586.38 kcal/mol for the vaccine-TLR-4 complex. These findings validate that the designed vaccine construct showed promising ability in terms of binding to immune receptors and may be capable of eliciting strong immune responses once administered to the host. Further evidence from experimentations in mice models is required to validate real immune protection of the designed vaccine construct against B. mallei. Full article
(This article belongs to the Special Issue Vaccines Targeting Bacterial Infections)
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17 pages, 1028 KiB  
Article
Impact of HLA Polymorphism on the Immune Response to Bacillus Anthracis Protective Antigen in Vaccination versus Natural Infection
by Stephanie Ascough, Rebecca J. Ingram, Karen K. Y. Chu, Stephen J. Moore, Theresa Gallagher, Hugh Dyson, Mehmet Doganay, Gökhan Metan, Yusuf Ozkul, Les Baillie, E. Diane Williamson, John H. Robinson, Bernard Maillere, Rosemary J. Boyton and Daniel M. Altmann
Vaccines 2022, 10(10), 1571; https://doi.org/10.3390/vaccines10101571 - 20 Sep 2022
Cited by 1 | Viewed by 2375
Abstract
The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies [...] Read more.
The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6. The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural infection and vaccination is vital in planning protective strategies against anthrax. Full article
(This article belongs to the Special Issue Vaccines Targeting Bacterial Infections)
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