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Vaccines
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Vaccines Against Antibiotic Resistant Bacteria: From Bench to Bedside
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Vaccines Against Antibiotic Resistant Bacteria: From Bench to Bedside

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

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 11840

Special Issue Editors

Dr. Michael J. McConnell

E-Mail Website
Guest Editor
Instituto de Salud Carlos III, Madrid, Spain
Interests: vaccines; antibiotic resistance; emerging infections
Dr. Mireia López Siles

E-Mail Website
Guest Editor
Department of Biology, Universitat de Girona, Catalonia, Spain
Interests: gut microbiota; biomarkers; pathogenesis; antimicrobial resistance; DNA vaccines
Dr. Andrés Corral Lugo

E-Mail Website
Guest Editor
National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain
Interests: animal models and vaccine development

Special Issue Information

Dear Colleagues,

The emergence and global dissemination of bacterial strains from numerous species with resistance to multiple antibiotic classes has increased over the recent years, both in the healthcare and the community setting. Nowadays antimicrobial resistance is a major threat to global public health which can be aggravated in the years to come.

To overcome this situation, in addition to existing approaches, novel strategies to fight against the most worrisome species, including both Gram-positive and Gram-negative bacteria, are required. In this context, vaccination has been proven as an effective approach to prevent and reduce bacterial infections. Despite the efforts of the scientific community over the past decades, it has not been successfully applied to infections caused by some of the most problematic antibiotic resistant pathogens.

We are pleased to invite you to contribute to this Special Issue with the aim to gather together studies elucidating the potential for vaccines to contribute to reducing the burden of disease of infections caused by antibiotic resistant bacteria, with special focus on pre-clinical studies.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following:

  • Genomic, proteomic or bioinformatics approaches for antigens identification, selection or immunogenicity assessment
  • In vitro development of candidate vaccines including different technologies from whole-cell to subunit or nucleic acid vaccines.
  • In vivo studies of immune response, including development of novel animal models or testing methodologies
  • Improvement on vaccine formulation, adjuvants, delivery methods and/or administration routes
  • Advances in vaccines production with special focus on regulatory affairs, commercial utilization, and policy safety considerations
  • Studies for vaccine personalization: effect on host’s microbiota, effect of host’s genetics, effect of host’s immune profile and epidemiology considerations for target population.

We look forward to receiving your manuscripts.

Dr. Michael J. McConnell
Dr. Mireia López-Siles
Dr. Andrés Corral Lugo
Guest Editors

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.

Published Papers (5 papers)

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Research

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20 pages, 3583 KiB  
Article
TonB-Dependent Receptor Protein Displayed on Spores of Bacillus subtilis Stimulates Protective Immune Responses against Acinetobacter baumannii
by Nor-Aziyah MatRahim, Kathryn Marie Jones, Brian P. Keegan, Ulrich Strych, Bin Zhan, Hai-Yen Lee and Sazaly AbuBakar
Vaccines 2023, 11(6), 1106; https://doi.org/10.3390/vaccines11061106 - 16 Jun 2023
Viewed by 1274
Abstract
The emergence of antibiotic-resistant Acinetobacter baumannii strains with limited treatment options has become a significant global health concern. Efforts to develop vaccines against the bacteria have centred on several potential protein targets, including the TonB-dependent receptors (TBDRs). In the present study, TBDRs from [...] Read more.
The emergence of antibiotic-resistant Acinetobacter baumannii strains with limited treatment options has become a significant global health concern. Efforts to develop vaccines against the bacteria have centred on several potential protein targets, including the TonB-dependent receptors (TBDRs). In the present study, TBDRs from A. baumannii were displayed on the surface of Bacillus subtilis spores. The immunogenicity of the recombinant spores was evaluated in orally vaccinated mice. None of the immunized mice demonstrated signs of illness and were observed to be healthy throughout the study. Sera and the intestinal secretions from the recombinant spores-treated mice demonstrated mucosal and humoral antibody responses to the vaccine antigen. In addition, bactericidal activities of the sera against A. baumannii clinical isolates were demonstrated. These observations suggest that the B. subtilis spore-displayed TBDRs should be further explored as much-needed potential oral vaccine candidates against A. baumannii. Full article
(This article belongs to the Special Issue Vaccines Against Antibiotic Resistant Bacteria: From Bench to Bedside)
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24 pages, 3892 KiB  
Article
Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis
by Mahnoor Malik, Saifullah Khan, Asad Ullah, Muhammad Hassan, Mahboob ul Haq, Sajjad Ahmad, Alhanouf I. Al-Harbi, Samira Sanami, Syed Ainul Abideen, Muhammad Irfan and Muhammad Khurram
Vaccines 2023, 11(2), 263; https://doi.org/10.3390/vaccines11020263 - 25 Jan 2023
Cited by 8 | Viewed by 2060
Abstract
The ongoing antibiotic-resistance crisis is becoming a global problem affecting public health. Urgent efforts are required to design novel therapeutics against pathogenic bacterial species. Brucella melitensis is an etiological agent of brucellosis, which mostly affects sheep and goats but several cases have also [...] Read more.
The ongoing antibiotic-resistance crisis is becoming a global problem affecting public health. Urgent efforts are required to design novel therapeutics against pathogenic bacterial species. Brucella melitensis is an etiological agent of brucellosis, which mostly affects sheep and goats but several cases have also been reported in cattle, water buffalo, yaks and dogs. Infected animals also represent the major source of infection for humans. Development of safer and effective vaccines for brucellosis remains a priority to support disease control and eradication in animals and to prevent infection to humans. In this research study, we designed an in-silico multi-epitopes vaccine for B. melitensis using computational approaches. The pathogen core proteome was screened for good vaccine candidates using subtractive proteomics, reverse vaccinology and immunoinformatic tools. In total, 10 proteins: catalase; siderophore ABC transporter substrate-binding protein; pyridoxamine 5′-phosphate oxidase; superoxide dismutase; peptidylprolyl isomerase; superoxide dismutase family protein; septation protein A; hypothetical protein; binding-protein-dependent transport systems inner membrane component; and 4-hydroxy-2-oxoheptanedioate aldolase were selected for epitopes prediction. To induce cellular and antibody base immune responses, the vaccine must comprise both B and T-cells epitopes. The epitopes were next screened for antigenicity, allergic nature and water solubility and the probable antigenic, non-allergic, water-soluble and non-toxic nine epitopes were shortlisted for multi-epitopes vaccine construction. The designed vaccine construct comprises 274 amino acid long sequences having a molecular weight of 28.14 kDa and instability index of 27.62. The vaccine construct was further assessed for binding efficacy with immune cell receptors. Docking results revealed that the designed vaccine had good binding potency with selected immune cell receptors. Furthermore, vaccine-MHC-I, vaccine-MHC-II and vaccine-TLR-4 complexes were opted based on a least-binding energy score of −5.48 kcal/mol, 0.64 kcal/mol and −2.69 kcal/mol. Those selected were then energy refined and subjected to simulation studies to understand dynamic movements of the docked complexes. The docking results were further validated through MMPBSA and MMGBSA analyses. The MMPBSA calculated −235.18 kcal/mol, −206.79 kcal/mol, and −215.73 kcal/mol net binding free energy, while MMGBSA estimated −259.48 kcal/mol, −206.79 kcal/mol and −215.73 kcal/mol for TLR-4, MHC-I and MHC-II complexes, respectively. These findings were validated by water-swap and entropy calculations. Overall, the designed vaccine construct can evoke proper immune responses and the construct could be helpful for experimental researchers in formulation of a protective vaccine against the targeted pathogen for both animal and human use. Full article
(This article belongs to the Special Issue Vaccines Against Antibiotic Resistant Bacteria: From Bench to Bedside)
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22 pages, 7318 KiB  
Article
Iron Acquisition Proteins of Pseudomonas aeruginosa as Potential Vaccine Targets: In Silico Analysis and In Vivo Evaluation of Protective Efficacy of the Hemophore HasAp
by Abdelrahman S. Hamad, Eva A. Edward, Eman Sheta, Hamida M. Aboushleib and Mohammed Bahey-El-Din
Vaccines 2023, 11(1), 28; https://doi.org/10.3390/vaccines11010028 - 23 Dec 2022
Cited by 2 | Viewed by 1567
Abstract
Background: Pseudomonas aeruginosa (PA) is a Gram-negative pathogen responsible for fatal nosocomial infections worldwide. Iron is essential for Gram-negative bacteria to establish an infection. Therefore, iron acquisition proteins (IAPs) of bacteria are attractive vaccine targets. Methodology: A “Reverse Vaccinology” approach was employed in [...] Read more.
Background: Pseudomonas aeruginosa (PA) is a Gram-negative pathogen responsible for fatal nosocomial infections worldwide. Iron is essential for Gram-negative bacteria to establish an infection. Therefore, iron acquisition proteins (IAPs) of bacteria are attractive vaccine targets. Methodology: A “Reverse Vaccinology” approach was employed in the current study. Expression levels of 37 IAPs in various types of PA infections were analyzed in seven previously published studies. The IAP vaccine candidate was selected based on multiple criteria, including a high level of expression, high antigenicity, solubility, and conservation among PA strains, utilizing suitable bioinformatics analysis tools. The selected IAP candidate was recombinantly expressed in Escherichia coli and purified using metal affinity chromatography. It was further evaluated in vivo for protection efficacy. The novel immune adjuvant, naloxone (NAL), was used. Results and discussion: HasAp antigen met all the in silico selection criteria, being highly antigenic, soluble, and conserved. In addition, it was the most highly expressed IAP in terms of average fold change compared to control. Although HasAp did excel in the in silico evaluation, subcutaneous immunization with recombinant HasAp alone or recombinant HasAp plus NAL (HasAP-NAL) did not provide the expected protection compared to controls. Immunized mice showed a low IgG2a/IgG1 ratio, indicating a T-helper type 2 (Th2)-oriented immune response that is suboptimal for protection against PA infections. Surprisingly, the bacterial count in livers of both NAL- and HasAp-NAL-immunized mice was significantly lower than the count in the HasAp and saline groups. The same trend was observed in kidneys and lungs obtained from these groups, although the difference was not significant. Such protection could be attributed to the enhancement of innate immunity by NAL. Conclusions: We provided a detailed in silico analysis of IAPs of PA followed by in vivo evaluation of the best IAP, HasAp. Despite the promising in silico results, HasAp did not provide the anticipated vaccine efficacy. HasAp should be further evaluated as a vaccine candidate through varying the immunization regimens, models of infection, and immunoadjuvants. Combination with other IAPs might also improve vaccination efficacy. We also shed light on several highly expressed promising IAPs whose efficacy as vaccine candidates is worthy of further investigation. Full article
(This article belongs to the Special Issue Vaccines Against Antibiotic Resistant Bacteria: From Bench to Bedside)
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14 pages, 2982 KiB  
Article
Bacterial Ghosts of Pseudomonas aeruginosa as a Promising Candidate Vaccine and Its Application in Diabetic Rats
by Salah A. Sheweita, Amro A. Amara, Heba Gamal, Amany A. Ghazy, Ahmed Hussein and Mohammed Bahey-El-Din
Vaccines 2022, 10(6), 910; https://doi.org/10.3390/vaccines10060910 - 07 Jun 2022
Cited by 3 | Viewed by 2147
Abstract
Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to immunocompromised patients. As a novel vaccine network for many kinds of bacteria, bacterial ghosts (BGs) have recently been introduced. In the present research, using Sponge-Like Reduced Protocol, P. [...] Read more.
Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to immunocompromised patients. As a novel vaccine network for many kinds of bacteria, bacterial ghosts (BGs) have recently been introduced. In the present research, using Sponge-Like Reduced Protocol, P. aeruginosa ghosts (PAGs) were prepared to maintain surface antigens and immunogenicity. This is the first study, to our knowledge, on the production of chemically induced well-structured bacterial ghosts for PA using concentrations of different chemicals. The research was carried out using diabetic rats who were orally immunized at two-week intervals with three doses of PAGs. Rats were subsequently challenged either by the oral route or by the model of ulcer infection with PA. In challenged rats, in addition to other immunological parameters, organ bioburden and wound healing were determined, respectively. Examination of the scanning and transmission electron microscope (EM) proved that PAGs with a proper three-dimensional structure were obtained. In contrast to control groups, oral PAGs promoted the generation of agglutinating antibodies, the development of IFN-γ, and the increase in phagocytic activity in vaccinated groups. Antibodies of the elicited PAGs were reactive to PA proteins and lipopolysaccharides. The defense against the PA challenge was observed in PAGs-immunized diabetic rats. The resulting PAGs in orally vaccinated diabetic rats were able to evoke unique humoral and cell-mediated immune responses and to defend them from the threat of skin wound infection. These results have positive implications for future studies on the PA vaccine. Full article
(This article belongs to the Special Issue Vaccines Against Antibiotic Resistant Bacteria: From Bench to Bedside)
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Review

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21 pages, 1422 KiB  
Review
The Potential Role of Vaccines in Preventing Antimicrobial Resistance (AMR): An Update and Future Perspectives
by Vincenzo Costanzo and Giovanni N. Roviello
Vaccines 2023, 11(2), 333; https://doi.org/10.3390/vaccines11020333 - 01 Feb 2023
Cited by 13 | Viewed by 3962
Abstract
In the modern era, the consumption of antibiotics represents a revolutionary weapon against several infectious diseases, contributing to the saving of millions of lives worldwide. However, the misuse of antibiotics for human and animal purposes has fueled the process of antimicrobial resistance (AMR), [...] Read more.
In the modern era, the consumption of antibiotics represents a revolutionary weapon against several infectious diseases, contributing to the saving of millions of lives worldwide. However, the misuse of antibiotics for human and animal purposes has fueled the process of antimicrobial resistance (AMR), considered now a global emergency by the World Health Organization (WHO), which significantly increases the mortality risk and related medical costs linked to the management of bacterial diseases. The current research aiming at developing novel efficient antibiotics is very challenging, and just a few candidates have been identified so far due to the difficulties connected with AMR. Therefore, novel therapeutic or prophylactic strategies to fight AMR are urgently needed. In this scenario, vaccines constitute a promising approach that proves to be crucial in preventing pathogen spreading in primary infections and in minimizing the usage of antibiotics following secondary bacterial infections. Unfortunately, most of the vaccines developed against the main resistant pathogens are still under preclinical and clinical evaluation due to the complexity of pathogens and technical difficulties. In this review, we describe not only the main causes of AMR and the role of vaccines in reducing the burden of infectious diseases, but we also report on specific prophylactic advancements against some of the main pathogens, focusing on new strategies that aim at improving vaccine efficiency. Full article
(This article belongs to the Special Issue Vaccines Against Antibiotic Resistant Bacteria: From Bench to Bedside)
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