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Vaccines
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Analysis and Modification of Existing Vaccines for the Development of...
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Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Attenuated/Inactivated/Live and Vectored Vaccines".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 29442

Special Issue Editor

Dr. Takashi Imai

E-Mail Website1 Website2
Guest Editor
1. Department of Microbiology, Saitama Medical University, Saitama, Japan
2. Department of Infectious Diseases and Host Defense, Gunma University, Gunma, Japan
Interests: malaria; malaria vaccine; DNA vaccine; cancer; infectious disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

The development of the first vaccine by Edward Jenner, “the father of immunology”, has proven to be one of the greatest innovations, saving countless lives. However, the emergence or recurrence of pathogens is an ongoing threat to humans, not least with the recent occurrence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Although the development and distribution of a vaccine against SARS-CoV-2 are urgently needed, other diseases should not be ignored. In this regard, the small modification of existing vaccines is likely to prove efficient for the development of versatile vaccines that are more stable for storage and represents an important step in the direction of the production of next-generation vaccines.

This Special Issue will focus on the analysis of the mode of action of current vaccines and their modification for the development of next-generation vaccines. The submission of articles covering the following research areas is encouraged:

  • Experimental characterization of vaccine;
  • Proof of concept of next-generation vaccines.

Dr. Takashi Imai
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

  • acquired immunity
  • immunological memory
  • cellular immunity
  • humoral immunity
  • DNA vaccine
  • live vaccine
  • subunit vaccine
  • next-generation vaccine
  • analysis
  • characterization
  • modification

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 173 KiB  
Editorial
Development of Next-Generation Vaccines
by Takashi Imai
Vaccines 2022, 10(2), 274; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10020274 - 10 Feb 2022
Viewed by 1212
Abstract
The battle between pathogens and hosts began on primitive Earth, and will probably continue forever [...] Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)

Research

Jump to: Editorial, Review

13 pages, 30913 KiB  
Article
Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens
by Kirill Vasilyev, Anna-Polina Shurygina, Natalia Zabolotnykh, Mariia Sergeeva, Ekaterina Romanovskaya-Romanko, Anastasia Pulkina, Janna Buzitskaya, Marine Z. Dogonadze, Tatiana I. Vinogradova and Marina A. Stukova
Vaccines 2021, 9(11), 1273; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9111273 - 03 Nov 2021
Cited by 7 | Viewed by 2346
Abstract
BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which [...] Read more.
BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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17 pages, 4095 KiB  
Article
Protective Efficacy of Novel Oral Biofilm Vaccines against Lactococcus garvieae Infection in Mullet, Mugil cephalus
by Feng-Jie Su and Meei-Mei Chen
Vaccines 2021, 9(8), 844; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9080844 - 01 Aug 2021
Cited by 11 | Viewed by 3012
Abstract
Lactococcus garvieae (L. garvieae) is an important pathogen that causes enormous economic losses in both marine and freshwater aquaculture. At present, antibiotics are the only option for farmers to reduce the losses caused by L. garvieae. However, the usage [...] Read more.
Lactococcus garvieae (L. garvieae) is an important pathogen that causes enormous economic losses in both marine and freshwater aquaculture. At present, antibiotics are the only option for farmers to reduce the losses caused by L. garvieae. However, the usage of antibiotics leads to environmental pollution and the production of drug-resistant strains of bacteria. Therefore, vaccination is preferred as an alternative method to prevent infectious diseases. In this study, we describe an effective approach to the production of an oral biofilm vaccine, using bacteria grown on chitosan particles to form biofilms, and thus providing an inactive pathogen that enhances the immune response in fish. We observed the formation of a biofilm on chitosan particles and administered the novel oral biofilm vaccine to fish. We analyzed the immune responses, including antibody production, phagocytic ability, albumin/globulin ratio and immune-related genes, of vaccinated and control groups of black mullet. Our results show that the phagocytic ability of the biofilm vaccine group was 84%, which is significantly higher than that of the control group, and the antibody production in this group was significantly higher compared with the other group. The mRNA expression levels of immune-related genes (TLR2, IL-1β, TNF-α) were significantly upregulated in the spleen after vaccination. In challenge experiments, the relative percent survival (RPS) was 77% in the biofilm vaccine group, 18% in the whole-cell vaccine group, and 0% in the chitosan particle group at 32 days post-vaccination. In addition, we also found that the relative percent survival (RPS) at 1 day post-vaccination was 74% in the biofilm vaccine group, 42% in the whole-cell vaccine group, and 26% in the chitosan particle group. In both long-term and short-term challenge experiments, the viability of the biofilm vaccine group was significantly higher than that of the whole-cell, chitosan particle and PBS groups. We conclude that based on its protective effect, the L. garvieae biofilm vaccine is better than the whole-cell vaccine when challenged several weeks after vaccination. In addition, the biofilm vaccine also has a greater protective effect than the whole-cell vaccine when challenged immediately after vaccination. Therefore, the biofilm vaccine might represent a novel method for the prevention and treatment of L. garvieae infection. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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11 pages, 1969 KiB  
Article
Optimization of Vero Cells Grown on a Polymer Fiber Carrier in a Disposable Bioreactor for Inactivated Coxsackievirus A16 Vaccine Development
by Keda Chen, Chaonan Li, Ying Wang, Zhenwei Shen, Yikai Guo, Xiaoping Li and Yanjun Zhang
Vaccines 2021, 9(6), 613; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9060613 - 07 Jun 2021
Cited by 5 | Viewed by 2544
Abstract
At present, there are no vaccines available for hand, foot, and mouth disease, which is caused by Coxsackie virus A16 (CVA16) infection. In the present study, we isolated epidemic strains of CVA16 and optimized the production of the virus in Vero cells. The [...] Read more.
At present, there are no vaccines available for hand, foot, and mouth disease, which is caused by Coxsackie virus A16 (CVA16) infection. In the present study, we isolated epidemic strains of CVA16 and optimized the production of the virus in Vero cells. The system comprised growing the infected cells on polymer fiber paper carriers in a serum-free medium containing 0.5% (w/v) lactalbumin hydrolysate a mini bioreactor. Disposable Bioflo310 and AmProtein Current perfusion bioreactors were used to monitor virus infection and Vero cell culture. The total number of cells increased from 1.5 × 109 to 3.0 × 1010. In our optimized culture process, the virus titer reached 7.8 × 107 TCID50/mL at three days after infection. The inactivated CVA16 prepared from our optimized culture procedure elicited a slightly higher neutralizing antibody titer compared with that derived from routine culture procedures. These results will promote the large-scale production of inactivated CVA16 vaccines using nonwoven polymer fiber paper cell cultures. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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11 pages, 2944 KiB  
Article
Single Amino Acid Deletion at N-Terminus of the Target Antigen in DNA Vaccine Induces Altered CD8+ T Cell Responses against Tumor Antigen
by Takashi Imai
Vaccines 2021, 9(6), 540; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9060540 - 21 May 2021
Cited by 3 | Viewed by 2202
Abstract
Since CD8+ T cells have immunological memory and can eliminate tumor or infected cells, antigen-specific CD8+ T cell inducing DNA vaccines are potential next-generation vaccines. However, the relationship between single amino acid deletion of target antigens in plasmid DNA vaccines and [...] Read more.
Since CD8+ T cells have immunological memory and can eliminate tumor or infected cells, antigen-specific CD8+ T cell inducing DNA vaccines are potential next-generation vaccines. However, the relationship between single amino acid deletion of target antigens in plasmid DNA vaccines and vaccine efficacy is not completely understood. To address this knowledge disparity and improve DNA vaccine development, two constructs cytosolic form of ovalbumin, pOVAv (346 amino acids) and pOVAy (345 amino acids) were constructed and compared. OVA proteins from both constructs were detected in an in vitro experiment. Then, the efficacy of prophylactic DNA vaccination using a gene gun against OVA-expressing mouse thymoma cells was compared. Both constructs conferred protection against tumor challenge, and there was no significant difference between the efficacies of pOVAv and pOVAy. The pOVAv vaccine induced stronger antigen-specific cytotoxicity in vivo, while bone marrow-derived dendritic cells (BMDCs) transfected with pOVAv induced higher levels of IFN-γ production from OT-I CD8+ T cells in vitro compared to pOVAy. These results indicate that a single amino acid deletion at N-terminus of the target antigen in a DNA vaccine leads to a different immunological outcome. The small modification of the target antigen in the DNA vaccine might improve its efficacy against tumor or infectious diseases. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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11 pages, 4499 KiB  
Article
An Oncolytic Adenovirus Encoding SA-4-1BBL Adjuvant Fused to HPV-16 E7 Antigen Produces a Specific Antitumor Effect in a Cancer Mouse Model
by Alejandra G. Martinez-Perez, Jose J. Perez-Trujillo, Rodolfo Garza-Morales, Norma E. Ramirez-Avila, Maria J. Loera-Arias, Jorge G. Gomez-Gutierrez, Odila Saucedo-Cardenas, Aracely Garcia-Garcia, Humberto Rodriguez-Rocha and Roberto Montes-de-Oca-Luna
Vaccines 2021, 9(2), 149; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9020149 - 12 Feb 2021
Cited by 14 | Viewed by 2678
Abstract
Human papillomaviruses (HPVs) are responsible for about 25% of cancer cases worldwide. HPV-16 E7 antigen is a tumor-associated antigen (TAA) commonly expressed in HPV-induced tumors; however, it has low immunogenicity. The interaction of 4-1BBL with its receptor induces pleiotropic effects on innate, adaptive, [...] Read more.
Human papillomaviruses (HPVs) are responsible for about 25% of cancer cases worldwide. HPV-16 E7 antigen is a tumor-associated antigen (TAA) commonly expressed in HPV-induced tumors; however, it has low immunogenicity. The interaction of 4-1BBL with its receptor induces pleiotropic effects on innate, adaptive, and regulatory immunity and, if fused to TAAs in DNA vaccines, can improve the antitumor response; however, there is low transfection and antitumor efficiency. Oncolytic virotherapy is promising for antitumor gene therapy as it can be selectively replicated in tumor cells, inducing cell lysis, and furthermore, tumor cell debris can be taken in by immune cells to potentiate antitumor responses. In this study, we expressed the immunomodulatory molecule SA-4-1BBL fused to E7 on an oncolytic adenovirus (OAd) system. In vitro infection of TC-1 tumor cells and NIH-3T3 non-tumor cells with SA/E7/4-1BBL OAd demonstrated that only tumor cells are selectively destroyed. Moreover, protein expression is targeted to the endoplasmic reticulum in both cell lines when a signal peptide (SP) is added. Finally, in an HPV-induced cancer murine model, the therapeutic oncolytic activity of OAd can be detected, and this can be improved when fused to E7 and SP. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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13 pages, 2348 KiB  
Article
Optimized Detoxification of a Live Attenuated Vaccine Strain (SG9R) to Improve Vaccine Strategy against Fowl Typhoid
by Nam-Hyung Kim, Dae-Sung Ko, Eun-Jin Ha, Sunmin Ahn, Kang-Seuk Choi and Hyuk-Joon Kwon
Vaccines 2021, 9(2), 122; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9020122 - 03 Feb 2021
Cited by 9 | Viewed by 2589
Abstract
The live attenuated vaccine strain, SG9R, has been used against fowl typhoid worldwide, but it can revert to the pathogenic smooth strain owing to single nucleotide changes such as nonsense mutations in the rfaJ gene. As SG9R possesses an intact Salmonella plasmid with [...] Read more.
The live attenuated vaccine strain, SG9R, has been used against fowl typhoid worldwide, but it can revert to the pathogenic smooth strain owing to single nucleotide changes such as nonsense mutations in the rfaJ gene. As SG9R possesses an intact Salmonella plasmid with virulence genes, it exhibits dormant pathogenicity and can cause fowl typhoid in young chicks and stressed or immunocompromised brown egg-laying hens. To tackle these issues, we knocked out the rfaJ gene of SG9R (named Safe-9R) to eliminate the reversion risk and generated detoxified strains of Safe-9R by knocking out lpxL, lpxM, pagP, and phoP/phoQ genes to attenuate the virulence. Among the knockout strains, live ΔlpxL- (Dtx-9RL) and ΔlpxM-9R (Dtx-9RM) strains induced remarkably less expression of inflammatory cytokines in chicken macrophage cells, and oil emulsion (OE) Dtx-9RL did not cause body weight loss in chicks. Live Dtx-9RM exhibited efficacy against field strain challenge in one week without any bacterial re-isolation, while the un-detoxified strains showed the development of severe liver lesions and re-isolation of challenged strains. Thus, SG9R was optimally detoxified by knockout of lpxL and lpxM, and Dtx-9RL and Dtx-9RM might be applicable as OE and live vaccines, respectively, to prevent fowl typhoid irrespective of the age of chickens. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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12 pages, 2319 KiB  
Article
Degradomics-Based Analysis of Tetanus Toxoids as a Quality Control Assay
by Thomas J. M. Michiels, Wichard Tilstra, Martin R. J. Hamzink, Justin W. de Ridder, Maarten Danial, Hugo D. Meiring, Gideon F. A. Kersten, Wim Jiskoot and Bernard Metz
Vaccines 2020, 8(4), 712; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8040712 - 01 Dec 2020
Cited by 7 | Viewed by 3319
Abstract
Currently, batch release of toxoid vaccines, such as diphtheria and tetanus toxoid, requires animal tests to confirm safety and immunogenicity. Efforts are being made to replace these tests with in vitro assays in a consistency approach. Limitations of current in vitro assays include [...] Read more.
Currently, batch release of toxoid vaccines, such as diphtheria and tetanus toxoid, requires animal tests to confirm safety and immunogenicity. Efforts are being made to replace these tests with in vitro assays in a consistency approach. Limitations of current in vitro assays include the need for reference antigens and most are only applicable to drug substance, not to the aluminum adjuvant-containing and often multivalent drug product. To overcome these issues, a new assay was developed based on mimicking the proteolytic degradation processes in antigen-presenting cells with recombinant cathepsin S, followed by absolute quantification of the formed peptides by liquid chromatography-mass spectrometry. Temperature-exposed tetanus toxoids from several manufacturers were used as aberrant samples and could easily be distinguished from the untreated controls by using the newly developed degradomics assay. Consistency of various batches of a single manufacturer could also be determined. Moreover, the assay was shown to be applicable to Al(OH)3 and AlPO4-adsorbed tetanus toxoids. Overall, the assay shows potential for use in both stability studies and as an alternative for in vivo potency studies by showing batch-to-batch consistency of bulk toxoids as well as for aluminum-containing vaccines. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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Graphical abstract

14 pages, 4591 KiB  
Article
Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC
by Shushan Harutyunyan, Irene Neuhauser, Alexandra Mayer, Michael Aichinger, Valéria Szijártó, Gábor Nagy, Eszter Nagy, Petra Girardi, Frank J. Malinoski and Tamás Henics
Vaccines 2020, 8(4), 689; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8040689 - 16 Nov 2020
Cited by 17 | Viewed by 3710
Abstract
Background: Shigella spp. and enterotoxigenic Escherichia coli (ETEC) remain the two leading bacterial causes of diarrheal diseases worldwide. Attempts to develop preventive vaccines against Shigella and ETEC have not yet been successful. The major challenge for a broad Shigella vaccine is the [...] Read more.
Background: Shigella spp. and enterotoxigenic Escherichia coli (ETEC) remain the two leading bacterial causes of diarrheal diseases worldwide. Attempts to develop preventive vaccines against Shigella and ETEC have not yet been successful. The major challenge for a broad Shigella vaccine is the serotype-specific immune response to the otherwise protective LPS O-antigen. ETEC vaccines mainly rely on the heat-labile enterotoxin (LT), while heat-stable toxin (ST) has also been shown to be an important virulence factor. Methods: We constructed a combined Shigella and ETEC vaccine (ShigETEC) based on a live attenuated Shigella strain rendered rough and non-invasive with heterologous expression of two ETEC antigens, LTB and a detoxified version of ST (STN12S). This new vaccine strain was characterized and tested for immunogenicity in relevant animal models. Results: Immunization with ShigETEC resulted in serotype independent protection in the mouse lung shigellosis model and induced high titer IgG and IgA antibodies against bacterial lysates, and anti-ETEC toxin antibodies with neutralizing capacity. Conclusions: ShigETEC is a promising oral vaccine candidate against Shigella and ETEC infections and currently in Phase 1 testing. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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Review

Jump to: Editorial, Research

16 pages, 992 KiB  
Review
Critical Assessment of Purification and Analytical Technologies for Enveloped Viral Vector and Vaccine Processing and Their Current Limitations in Resolving Co-Expressed Extracellular Vesicles
by Aline Do Minh and Amine A. Kamen
Vaccines 2021, 9(8), 823; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9080823 - 26 Jul 2021
Cited by 14 | Viewed by 4626
Abstract
Viral vectors and viral vaccines are invaluable tools in prevention and treatment of diseases. Many infectious diseases are controlled using vaccines designed from subunits or whole viral structures, whereas other genetic diseases and cancers are being treated by viruses used as vehicles for [...] Read more.
Viral vectors and viral vaccines are invaluable tools in prevention and treatment of diseases. Many infectious diseases are controlled using vaccines designed from subunits or whole viral structures, whereas other genetic diseases and cancers are being treated by viruses used as vehicles for delivering genetic material in gene therapy or as therapeutic agents in virotherapy protocols. Viral vectors and vaccines are produced in different platforms, from traditional embryonated chicken eggs to more advanced cell cultures. All these expression systems, like most cells and cellular tissues, are known to spontaneously release extracellular vesicles (EVs). EVs share similar sizes, biophysical characteristics and even biogenesis pathways with enveloped viruses, which are currently used as key ingredients in a number of viral vectors and licensed vaccine products. Herein, we review distinctive features and similarities between EVs and enveloped viruses as we revisit the downstream processing steps and analytical technologies currently implemented to produce and document viral vector and vaccine products. Within a context of well-established viral vector and vaccine safety profiles, this review provides insights on the likely presence of EVs in the final formulation of enveloped virus products and discusses the potential to further resolve and document these components. Full article
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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