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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Pathogens-host Immune Interface".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 30938

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Dr. Anke Osterloh

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Research Center Borstel, 23845 Sülfeld, Germany
Interests: rickettsioses; adaptive and innate immunity; immunopathology; antigen identification; vaccination

Special Issue Information

Dear Colleagues,

While there are vaccines against certain bacterial infectious diseases, such as cholera, diphtheria, pertussis, and typhoid fever, there is a lack of prophylactic vaccines against many other bacterial pathogens. This is especially true for neglected bacterial diseases that are emerging and/or related to poverty and unsanitary living conditions. Some of these bacterial infections, e.g., leptospirosis and rickettsial infections, affect billions of people, especially in developing countries, where they occur at high incidence, prevalence, and claim many lives.

Apart from a potentially high morbidity, prophylactic vaccines against various bacterial pathogens are needed for several other reasons. In general, the development of antibiotic resistance of bacterial pathogens is a major threat observed in an increasing number of bacterial species. This is especially a problem with bacteria that already respond to a very limited repertoire of antibiotics, making alternative drugs for treatment scarce. Finally, there is great concern that certain bacterial species could be used as bioterror weapons, e.g., the agents of anthrax, epidemic typhus, plague, and tularemia.

Knowledge of the immune mechanisms involved in protection and the immunogenic determinants of a pathogen is generally essential for vaccine development. In this regard, the development of vaccines against intracellular bacterial pathogens, whose defense requires special immune mechanisms, presents a particular challenge.

The aim of this Special Issue is to draw attention to research on bacterial infectious diseases, focusing on protective immune mechanisms and vaccine development. We invite you to submit articles for this Special Issue describing mechanisms of immunity to bacterial infections, immunogenic antigens of bacterial pathogens, systems of antigen delivery, and vaccination. We welcome both original research articles and reviews.

We look forward to receiving your contributions.

Dr. Anke Osterloh
Guest Editor

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Keywords

bacterial infections
protective immunity
immunogens
vaccines
antigen delivery

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Published Papers (10 papers)

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Research

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13 pages, 1932 KiB

Open AccessArticle

BCG Vaccination-Associated Lower HbA1c and Increased CD25 Expression on CD8⁺ T Cells in Patients with Type 1 Diabetes in Ghana

by Wilfred Aniagyei, Sumaya Mohayideen, Osei Sarfo-Kantanka, Sarah Bittner, Monika M. Vivekanandan, Joseph F. Arthur, Agnes O. Boateng, Augustine Yeboah, Hubert S. Ahor, Shadrack O. Asibey, Elizabeth Owusu, Diran Herebian, Maximilian Huttasch, Volker Burkart, Robert Wagner, Michael Roden, Ernest Adankwah, Dorcas O. Owusu, Ertan Mayatepek, Marc Jacobsen, Richard O. Phillips and Julia Seyfarth Show full author list Hide full author list

Vaccines 2024, 12(5), 452; https://doi.org/10.3390/vaccines12050452 - 24 Apr 2024

Viewed by 1718

Abstract

BCG vaccination affects other diseases beyond tuberculosis by unknown—potentially immunomodulatory—mechanisms. Recent studies have shown that BCG vaccination administered during overt type 1 diabetes (T1D) improved glycemic control and affected immune and metabolic parameters. Here, we comprehensively characterized Ghanaian T1D patients with or without routine neonatal BCG vaccination to identify vaccine-associated alterations. Ghanaian long-term T1D patients (n = 108) and matched healthy controls (n = 214) were evaluated for disease-related clinical, metabolic, and immunophenotypic parameters and compared based on their neonatal BCG vaccination status. The majority of study participants were BCG-vaccinated at birth and no differences in vaccination rates were detected between the study groups. Notably, glycemic control metrics, i.e., HbA1c and IDAA1c, showed significantly lower levels in BCG-vaccinated as compared to unvaccinated patients. Immunophenotype comparisons identified higher expression of the T cell activation marker CD25 on CD8⁺ T cells from BCG-vaccinated T1D patients. Correlation analysis identified a negative correlation between HbA1c levels and CD25 expression on CD8⁺ T cells. In addition, we observed fractional increases in glycolysis metabolites (phosphoenolpyruvate and 2/3-phosphoglycerate) in BCG-vaccinated T1D patients. These results suggest that neonatal BCG vaccination is associated with better glycemic control and increased activation of CD8⁺ T cells in T1D patients. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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13 pages, 4388 KiB

Open AccessArticle

Mycobacterium avium subsp. paratuberculosis Candidate Vaccine Strains Are Pro-apoptotic in RAW 264.7 Murine Macrophages

by Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk K. Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy and Denise K. Zinniel

Vaccines 2023, 11(6), 1085; https://doi.org/10.3390/vaccines11061085 - 10 Jun 2023

Cited by 2 | Viewed by 1778

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne’s disease, a severe gastroenteritis of ruminants. This study developed a model cell culture system to rapidly screen MAP mutants with vaccine potential for apoptosis. Two wild-type strains, a transposon mutant, and two deletion mutant MAP strains (MOI of 10 with 1.2 × 10⁶ CFU) were tested in murine RAW 264.7 macrophages to determine if they induce apoptosis and/or necrosis. Both deletion mutants were previously shown to be attenuated and immunogenic in primary bovine macrophages. All strains had similar growth rates, but cell morphology indicated that both deletion mutants were elongated with cell wall bulging. Cell death kinetics were followed by a real-time cellular assay to measure luminescence (apoptosis) and fluorescence (necrosis). A 6 h infection period was the appropriate time to assess apoptosis that was followed by secondary necrosis. Apoptosis was also quantified via DAPI-stained nuclear morphology and validated via flow cytometry. The combined analysis confirmed the hypothesis that candidate vaccine deletion mutants are pro-apoptotic in RAW 264.7 cells. In conclusion, the increased apoptosis seen in the deletion mutants correlates with the attenuated phenotype and immunogenicity observed in bovine macrophages, a property associated with good vaccine candidates. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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11 pages, 1235 KiB

Open AccessArticle

BCG-Vaccinated Children with Contact to Tuberculosis Patients Show Delayed Conversion of Mycobacterium tuberculosis-Specific IFN-γ Release

by Dorcas O. Owusu, Ernest Adankwah, Wilfred Aniagyei, Isaac Acheampong, Difery Minadzi, Augustine Yeboah, Joseph F. Arthur, Millicent Lamptey, Monika M. Vivekanandan, Mohammed K. Abass, Francis Kumbel, Francis Osei-Yeboah, Amidu Gawusu, Linda Batsa Debrah, Alexander Debrah, Ertan Mayatepek, Julia Seyfarth, Richard O. Phillips and Marc Jacobsen

Vaccines 2023, 11(4), 855; https://doi.org/10.3390/vaccines11040855 - 17 Apr 2023

Cited by 2 | Viewed by 3299

Abstract

Mycobacterium (M.) bovis BCG vaccination is recommended for healthy babies after birth in several countries with a high prevalence of tuberculosis, including Ghana. Previous studies showed that BCG vaccination prevents individuals from developing severe clinical manifestations of tuberculosis, but BCG vaccination effects on the induction of IFN-γ after M. tuberculosis infection have hardly been investigated. Here, we performed IFN-γ-based T-cell assays (i.e., IFN-γ Release Assay, IGRA; T-cell activation and maturation marker assay, TAM-TB) in children who had contact with index tuberculosis patients (contacts). These contacts were classified as either being BCG vaccinated at birth (n = 77) or non-BCG-vaccinated (n = 17) and were followed up at three timepoints for a period of one year to determine immune conversion after M. tuberculosis exposure and potential infection. At baseline and month 3, BCG-vaccinated contacts had significantly lower IFN-γ levels after stimulation with M. tuberculosis-specific proteins as compared to non-BCG-vaccinated contacts. This resulted in decreased proportions of positive IGRA results (BCG-vaccinated: 60% at baseline, 57% at month 3; non-BCG-vaccinated: 77% and 88%, respectively) at month 3. However, until month 12, immune conversion in BCG-vaccinated contacts led to balanced proportions in IGRA responders and IFN-γ expression between the study groups. TAM-TB assay analyses confirmed higher proportions of IFN-γ-positive T-cells in non-BCG-vaccinated contacts. Low proportions of CD38-positive M. tuberculosis-specific T-cells were only detected in non-BCG-vaccinated contacts at baseline. These results suggest that BCG vaccination causes delayed immune conversion as well as differences in the phenotype of M. tuberculosis-specific T-cells in BCG-vaccinated contacts of tuberculosis patients. These differences are immune biomarker candidates for protection against the development of severe clinical tuberculosis manifestations. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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14 pages, 683 KiB

Open AccessArticle

The Interferon-Gamma Release Assay versus the Tuberculin Skin Test in the Diagnosis of Mycobacterium tuberculosis Infection in BCG-Vaccinated Children and Adolescents Exposed or Not Exposed to Contagious TB

by Magdalena Druszczynska, Michal Seweryn, Sebastian Wawrocki, Anna Pankowska, Magdalena Godkowicz and Magdalena Kowalewska-Pietrzak

Vaccines 2023, 11(2), 387; https://doi.org/10.3390/vaccines11020387 - 7 Feb 2023

Cited by 4 | Viewed by 1795

Abstract

Background: Children have an increased risk of developing active tuberculosis (TB) after exposure to Mycobacterium tuberculosis (M.tb), and they are more likely to develop the most severe forms of TB. Rapid diagnosis and treatment of latent M.tb infection (LTBI) is essential to lessen the devastating consequences of TB in children. Objective: The aim of the study was to evaluate TST (tuberculin skin test) and IGRA (interferon-gamma release assay) utility in identifying LTBI in a cohort of Bacille Calmette–Guérin (BCG)-vaccinated Polish children and adolescents exposed or not exposed to contagious TB. In addition, we asked whether quantitative assessment of IGRA results could be valuable in predicting active TB disease. Results: Of the 235 recruited volunteers, 89 (38%) were TST-positive (TST+), 74 (32%) were IGRA-positive (IGRA+), and 62 (26%) were both TST+ and IGRA+. The frequency of TST positivity was significantly higher in the group with (59%) than without TB contact (18%). The percentage of TST+ subjects increased with age from 36% in the youngest children (<2 years) to 47% in the oldest group (>10 years). All positive IGRA results were found solely in the group of children with TB contact. There was a significant increase in the rate of positive IGRA results with age, from 9% in the youngest to 48% in the oldest group. The 10 mm TST cutoff showed good sensitivity and specificity in both TB exposed and nonexposed children and was associated with excellent negative predictive value, especially among nonexposed volunteers. Mean IFN-γ concentrations in IGRA cultures were significantly higher in the group of LTBI compared to the children with active TB disease, both TST+ and TST−. Conclusions: Both TST and IGRA can be used as screening tests for BCG-vaccinated children and adolescents exposed to contagious TB. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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13 pages, 1737 KiB

Open AccessArticle

Rickettsia Vaccine Candidate pVAX1-OmpB24 Stimulates TCD4+INF-γ+ and TCD8+INF-γ+ Lymphocytes in Autologous Co-Culture of Human Cells

by Karla Dzul-Rosado, Luis Donis-Maturano, Juan Arias-León, Jesús Machado-Contreras, Guillermo Valencia-Pacheco, Candi Panti-Balam, Javier Balam-Romero, Angela Ku-González, Gaspar Peniche-Lara, Juan Mosqueda, Oscar E. Zazueta, Cesar Lugo-Caballero and Fernando Puerto-Manzano

Vaccines 2023, 11(1), 173; https://doi.org/10.3390/vaccines11010173 - 13 Jan 2023

Cited by 1 | Viewed by 2558

Abstract

Background: In recent years, promising vaccination strategies against rickettsiosis have been described in experimental animal models and human cells. OmpB is considered an immunodominant antigen that is recognized by T and B cells. The aim of this study was to identify TCD4+INF-γ+ and TCD8+INF-γ+ lymphocytes in an autologous system with macrophages transfected with the vaccine candidate pVAX1-OmpB24. Lymphocytes and monocytes from 14 patients with Rickettsia were isolated from whole blood. Monocytes were differentiated into macrophages and transfected with the plasmid pVAX1-OmpB24 pVax1. Isolated lymphocytes were cultured with transfected macrophages. IFN-γ-producing TCD4+ and TCD8+ lymphocyte subpopulations were identified by flow cytometry, as was the percentage of macrophages expressing CD40+, CD80+, HLA-I and HLA-II. Also, we analyzed the exhausted condition of the T lymphocyte subpopulation by PD1 expression. Macrophages transfected with pVAX1-OmpB24 stimulated TCD4+INF-γ+ cells in healthy subjects and patients infected with R. typhi. Macrophages stimulated TCD8+INF-γ+ cells in healthy subjects and patients infected with R. rickettsii and R. felis. Cells from healthy donors stimulated with OmpB-24 showed a higher percentage of TCD4+PD1+. Cells from patients infected with R. rickettsii had a higher percentage of TCD8+PD-1+, and for those infected with R. typhi the larger number of cells corresponded to TCD4+PD1+. Human macrophages transfected with pVAX1-OmpB24 activated TCD4+IFN-γ+ and CD8+IFN-γ+ in patients infected with different Rickettsia species. However, PD1 expression played an important role in the inhibition of T lymphocytes with R. felis. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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21 pages, 2289 KiB

Open AccessArticle

Mycobacterium bovis Wild-Type BCG or Recombinant BCG Secreting Murine IL-18 (rBCG/IL-18) Strains in Driving Immune Responses in Immunocompetent or Immunosuppressed Mice

by Marek Fol, Marcin Włodarczyk, Magdalena Kowalewicz-Kulbat, Magdalena Druszczyńska, Krzysztof T. Krawczyk, Sebastian Wawrocki, Wiesława Rudnicka and Magdalena Chmiela

Vaccines 2022, 10(4), 615; https://doi.org/10.3390/vaccines10040615 - 14 Apr 2022

Viewed by 2716

Abstract

Mycobacterium tuberculosis infections remain a global health problem in immunosuppressed patients. The effectiveness of BCG (Bacillus Calmette–Guérin), an anti-tuberculosis vaccine, is unsatisfactory. Finding a new vaccine candidate is a priority. We compared numerous immune markers in BCG-susceptible C57BL/6 and BCG-resistant C3H mice who had been injected with 0.9% NaCl (control) or with wild-type BCG or recombinant BCG secreting interleukin (IL)-18 (rBCG/IL-18) and in immunized mice who were immunocompromised with cyclophosphamide (CTX). The inoculation of rBCG/IL-18 in immunocompetent mice increased the percentage of bone marrow myeloblasts and promyelocytes, which were further elevated in the rBCG/IL-18/CTX-treated mice: C57BL/6 mice—3.0% and 11.4% (control) vs. 18.6% and 42.4%, respectively; C3H mice—1.1% and 7.7% (control) vs. 18.4% and 44.9%, respectively, p < 0.05. The bone marrow cells showed an increased mean fluorescence index (MFI) in the CD34 adhesion molecules: C57BL/6 mice—4.0 × 10³ (control) vs. 6.2 × 10³; C3H mice—4.0 × 10³ (control) vs. 8.0 × 10³, p < 0.05. Even in the CTX-treated mice, the rBCG/IL-18 mobilized macrophages for phagocytosis, C57BL/6 mice—4% (control) vs. 8%; C3H mice—2% (control) vs. 6%, and in immunocompetent mice, C57BL/6 induced the spleen homing of effector memory CD4⁺ and CD8⁺ T cells (T_EM), 15% (control) vs. 28% and 8% (control) vs. 22%, respectively, p < 0.05. In conclusion, rBCG/IL-18 effectively induced selected immune determinants that were maintained even in immunocompromised mice. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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Review

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18 pages, 781 KiB

Open AccessReview

BCG and SARS-CoV-2—What Have We Learned?

by Jakub Kulesza, Ewelina Kulesza, Piotr Koziński, Wojciech Karpik, Marlena Broncel and Marek Fol

Vaccines 2022, 10(10), 1641; https://doi.org/10.3390/vaccines10101641 - 30 Sep 2022

Cited by 7 | Viewed by 2926

Abstract

Despite controversy over the protective effect of the BCG (Bacille Calmette-Guérin) vaccine in preventing pulmonary tuberculosis (TB) in adults, it has been used worldwide since 1921. Although the first reports in the 1930s had noted a remarkable decrease in child mortality after BCG immunization, this could not be explained solely by a decrease in mortality from TB. These observations gave rise to the suggestion of nonspecific beneficial effects of BCG vaccination, beyond the desired protection against M. tuberculosis. The existence of an innate immunity-training mechanism based on epigenetic changes was demonstrated several years ago. The emergence of the pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in 2019 revived the debate about whether the BCG vaccine can affect the immune response against the virus or other unrelated pathogens. Due to the mortality of the coronavirus disease (COVID-19), it is important to verify each factor that may have a potential protective value against the severe course of COVID-19, complications, and death. This paper reviews the results of numerous retrospective studies and prospective trials which shed light on the potential of a century-old vaccine to mitigate the pandemic impact of the new virus. It should be noted, however, that although there are numerous studies intending to verify the hypothesis that the BCG vaccine may have a beneficial effect on COVID-19, there is no definitive evidence on the efficacy of the BCG vaccine against SARS-CoV-2. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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14 pages, 339 KiB

Open AccessReview

A Vaccine for Canine Rocky Mountain Spotted Fever: An Unmet One Health Need

by David H. Walker, Lucas S. Blanton, Maureen Laroche, Rong Fang and Hema P. Narra

Vaccines 2022, 10(10), 1626; https://doi.org/10.3390/vaccines10101626 - 28 Sep 2022

Cited by 5 | Viewed by 2501

Abstract

Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health opportunity. The reality of the problem has been observed strikingly in Mexico, Brazil, Colombia, and Native American tribal lands in Arizona. The brown dog tick, Rhipicephalus sanguineus sensu lato, acquires the rickettsia from bacteremic dogs and can maintain the bacterium transtadially to the next tick stage. The subsequent adult tick can then transmit infection to a new host, as shown by guinea pig models. These brown dog ticks maintain spotted fever group rickettsiae transovarially through many generations, thus serving as both vector and reservoir. Vaccine containing whole-killed R. rickettsii does not stimulate sufficient immunity. Studies of Rickettsia subunit antigens have demonstrated that conformationally preserved outer-membrane autotransporter proteins A and B are the leading vaccine candidates. The possibility of a potentially safe and effective live attenuated vaccine has only begun to be explored as gene knockout methods are applied to these obligately intracellular pathogens. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

18 pages, 2993 KiB

Open AccessReview

NOD1, NOD2, and NLRC5 Receptors in Antiviral and Antimycobacterial Immunity

by Magdalena Godkowicz and Magdalena Druszczyńska

Vaccines 2022, 10(9), 1487; https://doi.org/10.3390/vaccines10091487 - 7 Sep 2022

Cited by 13 | Viewed by 2767

Abstract

The innate immune system recognizes pathogen-associated molecular motifs through pattern recognition receptors (PRRs) that induce inflammasome assembly in macrophages and trigger signal transduction pathways, thereby leading to the transcription of inflammatory cytokine genes. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) represent a family of cytosolic PRRs involved in the detection of intracellular pathogens such as mycobacteria or viruses. In this review, we discuss the role of NOD1, NOD2, and NLRC5 receptors in regulating antiviral and antimycobacterial immune responses by providing insight into molecular mechanisms as well as their potential health and disease implications. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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33 pages, 1784 KiB

Open AccessReview

Vaccination against Bacterial Infections: Challenges, Progress, and New Approaches with a Focus on Intracellular Bacteria

by Anke Osterloh

Vaccines 2022, 10(5), 751; https://doi.org/10.3390/vaccines10050751 - 10 May 2022

Cited by 16 | Viewed by 6478

Abstract

Many bacterial infections are major health problems worldwide, and treatment of many of these infectious diseases is becoming increasingly difficult due to the development of antibiotic resistance, which is a major threat. Prophylactic vaccines against these bacterial pathogens are urgently needed. This is also true for bacterial infections that are still neglected, even though they affect a large part of the world’s population, especially under poor hygienic conditions. One example is typhus, a life-threatening disease also known as “war plague” caused by Rickettsia prowazekii, which could potentially come back in a war situation such as the one in Ukraine. However, vaccination against bacterial infections is a challenge. In general, bacteria are much more complex organisms than viruses and as such are more difficult targets. Unlike comparatively simple viruses, bacteria possess a variety of antigens whose immunogenic potential is often unknown, and it is unclear which antigen can elicit a protective and long-lasting immune response. Several vaccines against extracellular bacteria have been developed in the past and are still used successfully today, e.g., vaccines against tetanus, pertussis, and diphtheria. However, while induction of antibody production is usually sufficient for protection against extracellular bacteria, vaccination against intracellular bacteria is much more difficult because effective defense against these pathogens requires T cell-mediated responses, particularly the activation of cytotoxic CD8⁺ T cells. These responses are usually not efficiently elicited by immunization with non-living whole cell antigens or subunit vaccines, so that other antigen delivery strategies are required. This review provides an overview of existing antibacterial vaccines and novel approaches to vaccination with a focus on immunization against intracellular bacteria. Full article

(This article belongs to the Special Issue Immunity and Vaccination against Bacterial Infections)

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