Vaccines

Research

11 pages, 1371 KiB

Open AccessArticle

Development and Validation of Enzyme-Linked Immunosorbent Assay for Group B Streptococcal Polysaccharide Vaccine

by A-Yeung Jang, Min-Joo Choi, Yong Zhi, Hyun-Jung Ji, Ji-Yun Noh, Jin-Gu Yoon, Hee-Jin Cheong, Woo-Joo Kim, Ho-Seong Seo and Joon-Young Song

Vaccines 2021, 9(6), 545; https://doi.org/10.3390/vaccines9060545 - 21 May 2021

Cited by 2 | Viewed by 2621

Abstract

Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of neonatal sepsis and meningitis in infants. Limitations of prenatal GBS screening and intrapartum antibiotic prophylaxis render developing GBS vaccines a high priority. In this study, we developed an enzyme-linked immunosorbent assay [...] Read more.

Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of neonatal sepsis and meningitis in infants. Limitations of prenatal GBS screening and intrapartum antibiotic prophylaxis render developing GBS vaccines a high priority. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) for the practical and large-scale evaluation of GBS capsular polysaccharide (PS) vaccine immunogenicity against three main serotypes, Ia, III, and V. GBS-ELISA was developed and subsequently validated using a standardized curve-fitting four-parameter logistic method. Specificity was measured using adsorption of serum with homologous and heterologous PS. Homologous adsorption showed a ≥75% inhibition of all three serotypes, whereas with heterologous PS, IgG GBS-ELISA inhibited only ≤25% of serotypes III and V. However, with serotype Ia, IgG antibody levels decreased by >50%, even after adsorption with heterologous PS (III or V). In comparison, the inhibition opsonophagocytic killing assay (OPA) of serotypes Ia GBS exhibited a reduction in opsonophagocytic activity of only 20% and 1.1% for serotypes III and V GBS, respectively. The precision of the GBS-ELISA was assessed in five independent experiments using four serum samples. The coefficient of variation was <5% for all three serotypes. This standardized GBS-ELISA would be useful for GBS vaccine development and its evaluation. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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13 pages, 1533 KiB

Open AccessArticle

Immune Responses to Irradiated Pneumococcal Whole Cell Vaccine

by Eunbyeol Ko, Soyoung Jeong, Min Yong Jwa, A Reum Kim, Ye-Eun Ha, Sun Kyung Kim, Sungho Jeong, Ki Bum Ahn, Ho Seong Seo, Cheol-Heui Yun and Seung Hyun Han

Vaccines 2021, 9(4), 405; https://doi.org/10.3390/vaccines9040405 - 19 Apr 2021

Cited by 2 | Viewed by 3034

Abstract

Streptococcus pneumoniae (pneumococcus) can cause respiratory and systemic diseases. Recently, γ-irradiation-inactivated, non-encapsulated, intranasal S. pneumoniae (r-SP) vaccine has been introduced as a novel serotype-independent and cost-effective vaccine. However, the immunogenic mechanism of r-SP is poorly understood. Here, we comparatively investigated the protective immunity [...] Read more.

Streptococcus pneumoniae (pneumococcus) can cause respiratory and systemic diseases. Recently, γ-irradiation-inactivated, non-encapsulated, intranasal S. pneumoniae (r-SP) vaccine has been introduced as a novel serotype-independent and cost-effective vaccine. However, the immunogenic mechanism of r-SP is poorly understood. Here, we comparatively investigated the protective immunity and immunogenicity of r-SP to the heat-(h-SP) or formalin-inactivated vaccine (f-SP) without adjuvants. Mice were intranasally immunized with each vaccine three times and then challenged with a lethal dose of S. pneumoniae TIGR4 strain and then subsequently evaluated for their immune responses. Immunization with r-SP elicited modestly higher protection against S. pneumoniae than h-SP or f-SP. Immunization with r-SP enhanced pneumococcal-specific IgA in the nasal wash and IgG in bronchoalveolar lavage fluid. Immunization with r-SP enhanced S. pneumoniae-specific IgG, IgG1, and IgG2b in the serum. r-SP more potently induced the maturation of dendritic cells in the cervical lymph nodes than h-SP or f-SP. Interestingly, populations of follicular helper T cells and IL-4-producing cells were potently increased in cervical lymph nodes of r-SP-immunized mice. Collectively, r-SP could be an effective intranasal, inactivated whole-cell vaccine in that it elicits S. pneumoniae-specific antibody production and follicular helper T cell activation leading to protective immune responses against S. pneumoniae infection. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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12 pages, 3252 KiB

Open AccessArticle

Roles of the Fc Receptor γ-Chain in Inducing Protective Immune Responses after Heterologous Vaccination against Respiratory Syncytial Virus Infection

by Hye Suk Hwang, Young-Tae Lee, Ki-Hye Kim, Ho Seong Seo, Kap Seung Yang, Hoonsung Cho and Sang-Moo Kang

Vaccines 2021, 9(3), 232; https://doi.org/10.3390/vaccines9030232 - 8 Mar 2021

Viewed by 2563

Abstract

The roles of the Fc receptor (FcR) in protection or inflammatory disease after respiratory syncytial virus (RSV) vaccination and infection remain unknown. Virus-like particles containing RSV fusion proteins (RSV F-VLPs) induce T-helper type 1 antibody responses and protection against RSV. Heterologous RSV F-VLP [...] Read more.

The roles of the Fc receptor (FcR) in protection or inflammatory disease after respiratory syncytial virus (RSV) vaccination and infection remain unknown. Virus-like particles containing RSV fusion proteins (RSV F-VLPs) induce T-helper type 1 antibody responses and protection against RSV. Heterologous RSV F-VLP prime and formalin-inactivated RSV (FI-RSV) boost vaccination has been reported to be effective in providing protection without inflammatory disease. Here, we investigated whether the FcRγ-chain is important for immune protection by the heterologous F-VLP and FI-RSV vaccination using FcRγ-chain knockout (−/−) mice. RSV F-VLP-primed and FI-RSV-boosted FcRγ −/− mice displayed less protective efficacy, as shown by higher lung viral titers upon RSV challenge, compared to RSV F-VLP-primed and FI-RSV-boosted immunized wild-type mice. RSV F-VLP and FI-RSV immunization induced lower levels of neutralizing activity and interferon-γ-producing CD8 T-cells in the bronchoalveolar lavage cells of FcRγ −/− mice than in those of wild-type mice. In addition, FcRγ −/− mice displayed a trend of enhancing lung histopathology after RSV vaccination and infection. This study suggests that the FcRγ-chain plays an important role in inducing antiviral protection and CD8 T-cell responses in RSV F-VLP prime and FI-RSV boost vaccination after RSV infections. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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17 pages, 2357 KiB

Open AccessArticle

Stability of Outer Membrane Vesicles-Based Vaccines, Identifying the Most Appropriate Methods to Detect Changes in Vaccine Potency

by Elena Palmieri, Vanessa Arato, Davide Oldrini, Beatrice Ricchetti, Maria Grazia Aruta, Werner Pansegrau, Sara Marchi, Fabiola Giusti, Ilaria Ferlenghi, Omar Rossi, Renzo Alfini, Carlo Giannelli, Gianmarco Gasperini, Francesca Necchi and Francesca Micoli

Vaccines 2021, 9(3), 229; https://doi.org/10.3390/vaccines9030229 - 6 Mar 2021

Cited by 17 | Viewed by 3684

Abstract

Ensuring the stability of vaccines is crucial to successfully performing global immunization programs. Outer Membrane Vesicles (OMV) are receiving great attention as vaccine platforms. OMV are complex molecules and few data have been collected so far on their stability. OMV produced by bacteria, [...] Read more.

Ensuring the stability of vaccines is crucial to successfully performing global immunization programs. Outer Membrane Vesicles (OMV) are receiving great attention as vaccine platforms. OMV are complex molecules and few data have been collected so far on their stability. OMV produced by bacteria, genetically modified to increase their spontaneous release, simplifying their production, are also known as Generalized Modules for Membrane Antigens (GMMA). We have performed accelerated stability studies on GMMA from different pathogens and verified the ability of physico-chemical and immunological methods to detect possible changes. High-temperature conditions (100 °C for 40 min) did not affect GMMA stability and immunogenicity in mice, in contrast to the effect of milder temperatures for a longer period of time (37 °C or 50 °C for 4 weeks). We identified critical quality attributes to monitor during stability assessment that could impact vaccine efficacy. In particular, specific recognition of antigens by monoclonal antibodies through competitive ELISA assays may replace in vivo tests for the potency assessment of GMMA-based vaccines. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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17 pages, 3701 KiB

Open AccessArticle

Salmonella Vaccine Vector System for Foot-and-Mouth Disease Virus and Evaluation of Its Efficacy with Virus-Like Particles

by Yong Zhi, Hyun Jung Ji, Huichen Guo, Jae Hyang Lim, Eui-Baek Byun, Woo Sik Kim and Ho Seong Seo

Vaccines 2021, 9(1), 22; https://doi.org/10.3390/vaccines9010022 - 5 Jan 2021

Cited by 5 | Viewed by 3671

Abstract

Foot-and-mouth disease virus (FMDV) causes a highly contagious and devastating disease in livestock animals and has a great potential to cause severe economic loss worldwide. The major antigen of FMDV capsid protein, VP1, contains the major B-cell epitope responsible for effectively eliciting protective [...] Read more.

Foot-and-mouth disease virus (FMDV) causes a highly contagious and devastating disease in livestock animals and has a great potential to cause severe economic loss worldwide. The major antigen of FMDV capsid protein, VP1, contains the major B-cell epitope responsible for effectively eliciting protective humoral immunity. In this study, irradiated Salmonella Typhimurium (KST0666) were used as transgenic vectors containing stress-inducible plasmid pRECN-VP1 to deliver the VP1 protein from FMDV-type A/WH/CHA/09. Mice were orally inoculated with ATOMASal-L3 harboring pRECN-VP1, and FMDV virus-like particles, where (VLP_FMDV)-specific humoral, mucosal, and cellular immune responses were evaluated. Mice vaccinated with attenuated Salmonella (KST0666) expressing VP1 (named KST0669) showed high levels of VLP-specific IgA in feces and IgG in serum, with high FMDV neutralization titer. Moreover, KST0669-vaccinated mice showed increased population of IFN-γ (type 1 T helper cells; Th1 cells)-, IL-5 (Th2 cells)-, and IL-17A (Th17 cells)-expressing CD4⁺ as well as activated CD8⁺ T cells (IFN-γ⁺CD8⁺ cells), detected by stimulating VLP_FMDV. All data indicate that our Salmonella vector system successfully delivered FMDV VP1 to immune cells and that the humoral and cellular efficacy of the vaccine can be easily evaluated using VLP_FMDV in a Biosafety Level I (BSL1) laboratory. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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10 pages, 621 KiB

Open AccessArticle

Bacterial Immunogenicity Prediction by Machine Learning Methods

by Ivan Dimitrov, Nevena Zaharieva and Irini Doytchinova

Vaccines 2020, 8(4), 709; https://doi.org/10.3390/vaccines8040709 - 30 Nov 2020

Cited by 12 | Viewed by 3581

Abstract

The identification of protective immunogens is the most important and vigorous initial step in the long-lasting and expensive process of vaccine design and development. Machine learning (ML) methods are very effective in data mining and in the analysis of big data such as [...] Read more.

The identification of protective immunogens is the most important and vigorous initial step in the long-lasting and expensive process of vaccine design and development. Machine learning (ML) methods are very effective in data mining and in the analysis of big data such as microbial proteomes. They are able to significantly reduce the experimental work for discovering novel vaccine candidates. Here, we applied six supervised ML methods (partial least squares-based discriminant analysis, k nearest neighbor (kNN), random forest (RF), support vector machine (SVM), random subspace method (RSM), and extreme gradient boosting) on a set of 317 known bacterial immunogens and 317 bacterial non-immunogens and derived models for immunogenicity prediction. The models were validated by internal cross-validation in 10 groups from the training set and by the external test set. All of them showed good predictive ability, but the xgboost model displays the most prominent ability to identify immunogens by recognizing 84% of the known immunogens in the test set. The combined RSM-kNN model was the best in the recognition of non-immunogens, identifying 92% of them in the test set. The three best performing ML models (xgboost, RSM-kNN, and RF) were implemented in the new version of the server VaxiJen, and the prediction of bacterial immunogens is now based on majority voting. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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14 pages, 11344 KiB

Open AccessArticle

Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine

by Woo Sik Kim, DaeSeong Choi, Ji Min Park, Ha-Yeon Song, Ho Seong Seo, Dong-Eun Lee and Eui-Baek Byun

Vaccines 2020, 8(4), 699; https://doi.org/10.3390/vaccines8040699 - 19 Nov 2020

Cited by 21 | Viewed by 3398

Abstract

Cancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-induced tumor exosomes have [...] Read more.

Cancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-induced tumor exosomes have may provide novel therapeutic approaches and more effective vaccine designs. Here, we confirmed the phenotypical and functional alterations of dendritic cells (DCs), which act as a bridge between the innate and adaptive arms of immunity, following non-irradiated (N-exo) and gamma-irradiated melanoma cancer cell-derived exosome (G-exo) stimulation, and evaluated the N-exo- and G-exo-stimulated DCs as therapeutic cancer vaccine candidates. We demonstrated that G-exo-stimulated DCs result in DC maturation by the upregulation of surface molecule expression, pro-inflammatory cytokine release, and antigen-presenting ability, and the downregulation of endocytic capacity. In addition, these cells promoted T cell proliferation and the generation of T helper type 1 (Th1) and interferon (IFN)-γ-producing CD8⁺ T cells. However, N-exo-stimulated DCs induced semi-mature phenotypes and functions, eventually inhibiting T cell proliferation, decreasing IFN-γ, and increasing IL-10-producing CD4⁺ T cells. In addition, although N-exo and G-exo stimulations showed similar levels of antigen-specific IFN-γ production, which served as tumor antigen sources in melanoma-specific T cells, G-exo-stimulated DC vaccination conferred a stronger tumor growth inhibition than N-exo-stimulated DC vaccination; further, this was accompanied by a high frequency of tumor-specific, multifunctional effector T cells. These results suggest that gamma irradiation could provide important clues for designing and developing effective exosome vaccines that can induce strong immunogenicity, especially tumor-specific multifunctional T cell responses. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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Review

Jump to: Research, Other

14 pages, 1890 KiB

Open AccessReview

The Immune Correlates of Orthohantavirus Vaccine

by Joon-Yong Bae, Jin Il Kim, Mee Sook Park, Gee Eun Lee, Heedo Park, Ki-Joon Song and Man-Seong Park

Vaccines 2021, 9(5), 518; https://doi.org/10.3390/vaccines9050518 - 18 May 2021

Cited by 2 | Viewed by 3035

Abstract

Zoonotic transmission of orthohantaviruses from rodent reservoirs to humans has been the cause of severe fatalities. Human infections are reported worldwide, but vaccines have been approved only in China and Korea. Orthohantavirus vaccine development has been pursued with no sense of urgency due [...] Read more.

Zoonotic transmission of orthohantaviruses from rodent reservoirs to humans has been the cause of severe fatalities. Human infections are reported worldwide, but vaccines have been approved only in China and Korea. Orthohantavirus vaccine development has been pursued with no sense of urgency due to the relative paucity of cases in countries outside China and Korea. However, the orthohantaviruses continuously evolve in hosts and thus the current vaccine may not work as well against some variants. Therefore, a more effective vaccine should be prepared against the orthohantaviruses. In this review, we discuss the issues caused by the orthohantavirus vaccine. Given the pros and cons of the orthohantavirus vaccine, we suggest strategies for the development of better vaccines in terms of pandemic preparedness. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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Other

Jump to: Research, Review

8 pages, 705 KiB

Open AccessPerspective

Evaluating Functional Immunity Following Encapsulated Bacterial Infection and Vaccination

by Zheng Quan Toh, Rachel A. Higgins, Nadia Mazarakis, Elysia Abbott, Jordan Nathanielsz, Anne Balloch, Kim Mulholland and Paul V. Licciardi

Vaccines 2021, 9(6), 677; https://doi.org/10.3390/vaccines9060677 - 20 Jun 2021

Cited by 6 | Viewed by 6300

Abstract

Encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis cause significant morbidity and mortality in young children despite the availability of vaccines. Highly specific antibodies are the primary mechanism of protection against invasive disease. Robust and standardised assays [...] Read more.

Encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis cause significant morbidity and mortality in young children despite the availability of vaccines. Highly specific antibodies are the primary mechanism of protection against invasive disease. Robust and standardised assays that measure functional antibodies are also necessary for vaccine evaluation and allow for the accurate comparison of data between clinical studies. This mini review describes the current state of functional antibody assays and their importance in measuring protective immunity. Full article

(This article belongs to the Special Issue Vaccine Evaluation Methods and Studies)

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