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3 pages, 201 KiB

Open AccessEditorial

Molecular Immunology in Bacterial Vaccine Discovery

by Rita Berisio

Cells 2022, 11(23), 3803; https://doi.org/10.3390/cells11233803 - 28 Nov 2022

Viewed by 1088

Abstract

The global threat of antimicrobial resistance (AMR) poses a difficult challenge, as underscored by the World Health Organization (WHO), which identifies AMR as one of the three greatest threats to human health [...] Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

Review

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16 pages, 2881 KiB

Open AccessReview

Thinking Outside the Bug: Targeting Outer Membrane Proteins for Burkholderia Vaccines

by Megan E. Grund, Jeon Choi Soo, Christopher K. Cote, Rita Berisio and Slawomir Lukomski

Cells 2021, 10(3), 495; https://doi.org/10.3390/cells10030495 - 25 Feb 2021

Cited by 12 | Viewed by 3210

Abstract

Increasing antimicrobial resistance due to misuse and overuse of antimicrobials, as well as a lack of new and innovative antibiotics in development has become an alarming global threat. Preventative therapeutics, like vaccines, are combative measures that aim to stop infections at the source, [...] Read more.

Increasing antimicrobial resistance due to misuse and overuse of antimicrobials, as well as a lack of new and innovative antibiotics in development has become an alarming global threat. Preventative therapeutics, like vaccines, are combative measures that aim to stop infections at the source, thereby decreasing the overall use of antibiotics. Infections due to Gram-negative pathogens pose a significant treatment challenge because of substantial multidrug resistance that is acquired and spread throughout the bacterial population. Burkholderia spp. are Gram-negative intrinsically resistant bacteria that are responsible for environmental and nosocomial infections. The Burkholderia cepacia complex are respiratory pathogens that primarily infect immunocompromised and cystic fibrosis patients, and are acquired through contaminated products and equipment, or via patient-to-patient transmission. The Burkholderia pseudomallei complex causes percutaneous wound, cardiovascular, and respiratory infections. Transmission occurs through direct exposure to contaminated water, water-vapors, or soil, leading to the human disease melioidosis, or the equine disease glanders. Currently there is no licensed vaccine against any Burkholderia pathogen. This review will discuss Burkholderia vaccine candidates derived from outer membrane proteins, OmpA, OmpW, Omp85, and Bucl8, encompassing their structures, conservation, and vaccine formulation. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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20 pages, 3523 KiB

Open AccessReview

PE_PGRS33, an Important Virulence Factor of Mycobacterium tuberculosis and Potential Target of Host Humoral Immune Response

by Eliza Kramarska, Flavia Squeglia, Flavio De Maio, Giovanni Delogu and Rita Berisio

Cells 2021, 10(1), 161; https://doi.org/10.3390/cells10010161 - 15 Jan 2021

Cited by 16 | Viewed by 3796

Abstract

PE_PGRS proteins are surface antigens of Mycobacterium tuberculosis (Mtb) and a few other pathogenic mycobacteria. The PE_PGRS33 protein is among the most studied PE_PGRSs. It is known that the PE domain of PE_PGRS33 is required for the protein translocation through the [...] Read more.

PE_PGRS proteins are surface antigens of Mycobacterium tuberculosis (Mtb) and a few other pathogenic mycobacteria. The PE_PGRS33 protein is among the most studied PE_PGRSs. It is known that the PE domain of PE_PGRS33 is required for the protein translocation through the mycobacterial cell wall, where the PGRS domain remains available for interaction with host receptors. Interaction with Toll like receptor 2 (TLR2) promotes secretion of inflammatory chemokines and cytokines, which are key in the immunopathogenesis of tuberculosis (TB). In this review, we briefly address some key challenges in the development of a TB vaccine and attempt to provide a rationale for the development of new vaccines aimed at fostering a humoral response against Mtb. Using PE_PGRS33 as a model for a surface-exposed antigen, we exploit the availability of current structural data using homology modeling to gather insights on the PGRS domain features. Our study suggests that the PGRS domain of PE_PGRS33 exposes four PGII sandwiches on the outer surface, which, we propose, are directly involved through their loops in the interactions with the host receptors and, as such, are promising targets for a vaccination strategy aimed at inducing a humoral response. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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17 pages, 808 KiB

Open AccessReview

Developing New Anti-Tuberculosis Vaccines: Focus on Adjuvants

by Ana Rita Franco and Francesco Peri

Cells 2021, 10(1), 78; https://doi.org/10.3390/cells10010078 - 5 Jan 2021

Cited by 20 | Viewed by 4629

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that sits in the top 10 leading causes of death in the world today and is the current leading cause of death among infectious diseases. Although there is a licensed vaccine against [...] Read more.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that sits in the top 10 leading causes of death in the world today and is the current leading cause of death among infectious diseases. Although there is a licensed vaccine against TB, the Mycobacterium bovis bacilli Calmette–Guérin (BCG) vaccine, it has several limitations, namely its high variability of efficacy in the population and low protection against pulmonary tuberculosis. New vaccines for TB are needed. The World Health Organization (WHO) considers the development and implementation of new TB vaccines to be a priority. Subunit vaccines are promising candidates since they can overcome safety concerns and optimize antigen targeting. Nevertheless, these vaccines need adjuvants in their formulation in order to increase immunogenicity, decrease the needed antigen dose, ensure a targeted delivery and optimize the antigens delivery and interaction with the immune cells. This review aims to focus on adjuvants being used in new formulations of TB vaccines, namely candidates already in clinical trials and others in preclinical development. Although no correlates of protection are defined, most research lines in the field of TB vaccination focus on T-helper 1 (Th1) type of response, namely polyfunctional CD4+ cells expressing simultaneously IFN-γ, TNF-α, and IL-2 cytokines, and also Th17 responses. Accordingly, most of the adjuvants reviewed here are able to promote such responses. In the future, it might be advantageous to consider a wider array of immune parameters to better understand the role of adjuvants in TB immunity and establish correlates of protection. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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19 pages, 4662 KiB

Open AccessReview

Current Status on Therapeutic Molecules Targeting Siglec Receptors

by María Pia Lenza, Unai Atxabal, Iker Oyenarte, Jesús Jiménez-Barbero and June Ereño-Orbea

Cells 2020, 9(12), 2691; https://doi.org/10.3390/cells9122691 - 15 Dec 2020

Cited by 32 | Viewed by 6474

Abstract

The sialic acid-binding immunoglobulin-type of lectins (Siglecs) are receptors that recognize sialic acid-containing glycans. In the majority of the cases, Siglecs are expressed on immune cells and play a critical role in regulating immune cell signaling. Over the years, it has been shown [...] Read more.

The sialic acid-binding immunoglobulin-type of lectins (Siglecs) are receptors that recognize sialic acid-containing glycans. In the majority of the cases, Siglecs are expressed on immune cells and play a critical role in regulating immune cell signaling. Over the years, it has been shown that the sialic acid-Siglec axis participates in immunological homeostasis, and that any imbalance can trigger different pathologies, such as autoimmune diseases or cancer. For all this, different therapeutics have been developed that bind to Siglecs, either based on antibodies or being smaller molecules. In this review, we briefly introduce the Siglec family and we compile a description of glycan-based molecules and antibody-based therapies (including CAR-T and bispecific antibodies) that have been designed to therapeutically targeting Siglecs. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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16 pages, 1556 KiB

Open AccessReview

Recent Advances in the Development of Protein- and Peptide-Based Subunit Vaccines against Tuberculosis

by Chiara Bellini and Kata Horváti

Cells 2020, 9(12), 2673; https://doi.org/10.3390/cells9122673 - 15 Dec 2020

Cited by 26 | Viewed by 6231

Abstract

The World Health Organization (WHO) herald of the “End TB Strategy” has defined goals and targets for tuberculosis prevention, care, and control to end the global tuberculosis endemic. The emergence of drug resistance and the relative dreadful consequences in treatment outcome has led [...] Read more.

The World Health Organization (WHO) herald of the “End TB Strategy” has defined goals and targets for tuberculosis prevention, care, and control to end the global tuberculosis endemic. The emergence of drug resistance and the relative dreadful consequences in treatment outcome has led to increased awareness on immunization against Mycobacterium tuberculosis (Mtb). However, the proven limited efficacy of Bacillus Calmette-Guérin (BCG), the only licensed vaccine against Mtb, has highlighted the need for alternative vaccines. In this review, we seek to give an overview of Mtb infection and failure of BCG to control it. Afterward, we focus on the protein- and peptide-based subunit vaccine subtype, examining the advantages and drawbacks of using this design approach. Finally, we explore the features of subunit vaccine candidates currently in pre-clinical and clinical evaluation, including the antigen repertoire, the exploited adjuvanted delivery systems, as well as the spawned immune response. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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22 pages, 381 KiB

Open AccessReview

Current Advances in Burkholderia Vaccines Development

by Guanbo Wang, Paulina Zarodkiewicz and Miguel A. Valvano

Cells 2020, 9(12), 2671; https://doi.org/10.3390/cells9122671 - 11 Dec 2020

Cited by 17 | Viewed by 3563

Abstract

The genus Burkholderia includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are Burkholderia mallei, Burkholderia pseudomallei, and the members of the Burkholderia cepacia complex (Bcc). B. mallei [...] Read more.

The genus Burkholderia includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are Burkholderia mallei, Burkholderia pseudomallei, and the members of the Burkholderia cepacia complex (Bcc). B. mallei and B. pseudomallei, the cause of glanders and melioidosis, respectively, are considered potential bioweapons. The Bcc comprises a subset of Burkholderia species associated with respiratory infections in people with chronic granulomatous disease and cystic fibrosis. Antimicrobial treatment of Burkholderia infections is difficult due to the intrinsic multidrug antibiotic resistance of these bacteria; prophylactic vaccines provide an attractive alternative to counteract these infections. Although commercial vaccines against Burkholderia infections are still unavailable, substantial progress has been made over recent years in the development of vaccines against B. pseudomallei and B. mallei. This review critically discusses the current advances in vaccine development against B. mallei, B. pseudomallei, and the Bcc. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

47 pages, 2417 KiB

Open AccessReview

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

by Maite Sainz-Mejías, Irene Jurado-Martín and Siobhán McClean

Cells 2020, 9(12), 2617; https://doi.org/10.3390/cells9122617 - 5 Dec 2020

Cited by 40 | Viewed by 12180

Abstract

Pseudomonas aeruginosa is a leading cause of chronic respiratory infections in people with cystic fibrosis (CF), bronchiectasis or chronic obstructive pulmonary disease (COPD), and acute infections in immunocompromised individuals. The adaptability of this opportunistic pathogen has hampered the development of antimicrobial therapies, and [...] Read more.

Pseudomonas aeruginosa is a leading cause of chronic respiratory infections in people with cystic fibrosis (CF), bronchiectasis or chronic obstructive pulmonary disease (COPD), and acute infections in immunocompromised individuals. The adaptability of this opportunistic pathogen has hampered the development of antimicrobial therapies, and consequently, it remains a major threat to public health. Due to its antimicrobial resistance, vaccines represent an alternative strategy to tackle the pathogen, yet despite over 50 years of research on anti-Pseudomonas vaccines, no vaccine has been licensed. Nevertheless, there have been many advances in this field, including a better understanding of the host immune response and the biology of P. aeruginosa. Multiple antigens and adjuvants have been investigated with varying results. Although the most effective protective response remains to be established, it is clear that a polarised Th2 response is sub-optimal, and a mixed Th1/Th2 or Th1/Th17 response appears beneficial. This comprehensive review collates the current understanding of the complexities of P. aeruginosa-host interactions and its implication in vaccine design, with a view to understanding the current state of Pseudomonal vaccine development and the direction of future efforts. It highlights the importance of the incorporation of appropriate adjuvants to the protective antigen to yield optimal protection. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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17 pages, 609 KiB

Open AccessReview

Advances and Prospects in Vaccine Development against Enterococci

by Ermioni Kalfopoulou and Johannes Huebner

Cells 2020, 9(11), 2397; https://doi.org/10.3390/cells9112397 - 2 Nov 2020

Cited by 9 | Viewed by 3260

Abstract

Enterococci are the second most common Gram-positive pathogen responsible for nosocomial infections. Due to the limited number of new antibiotics that reach the medical practice and the resistance of enterococci to the current antibiotic options, passive and active immunotherapies have emerged as a [...] Read more.

Enterococci are the second most common Gram-positive pathogen responsible for nosocomial infections. Due to the limited number of new antibiotics that reach the medical practice and the resistance of enterococci to the current antibiotic options, passive and active immunotherapies have emerged as a potential prevention and/or treatment strategy against this opportunistic pathogen. In this review, we explore the pathogenicity of these bacteria and their interaction with the host immune response. We provide an overview of the capsular polysaccharides and surface-associated proteins that have been described as potential antigens in anti-enterococcal vaccine formulations. In addition, we describe the current status in vaccine development against enterococci and address the importance and the current advances toward the development of well-defined vaccines with broad coverage against enterococci. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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16 pages, 2739 KiB

Open AccessReview

Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

by Samuel T. Pasco and Juan Anguita

Cells 2020, 9(9), 2109; https://doi.org/10.3390/cells9092109 - 16 Sep 2020

Cited by 15 | Viewed by 6541

Abstract

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has [...] Read more.

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined. Full article

(This article belongs to the Special Issue Molecular Immunology in Bacterial Vaccine Discovery)

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