Vaccines

20 pages, 230 KiB

Open AccessReview

Subunit Vaccine Approaches for African Swine Fever Virus

by Natasha N. Gaudreault and Juergen A. Richt

Vaccines 2019, 7(2), 56; https://doi.org/10.3390/vaccines7020056 - 25 Jun 2019

Cited by 90 | Viewed by 10493

African swine fever virus (ASFV) is the cause of a highly fatal disease in swine, for which there is no available vaccine. The disease is highly contagious and poses a serious threat to the swine industry worldwide. Since its introduction to the Caucasus [...] Read more.

African swine fever virus (ASFV) is the cause of a highly fatal disease in swine, for which there is no available vaccine. The disease is highly contagious and poses a serious threat to the swine industry worldwide. Since its introduction to the Caucasus region in 2007, a highly virulent, genotype II strain of ASFV has continued to circulate and spread into Eastern Europe and Russia, and most recently into Western Europe, China, and various countries of Southeast Asia. This review summarizes various ASFV vaccine strategies that have been investigated, with focus on antigen-, DNA-, and virus vector-based vaccines. Known ASFV antigens and the determinants of protection against ASFV versus immunopathological enhancement of infection and disease are also discussed. Full article

(This article belongs to the Special Issue Vaccines targeting African Swine Fever Virus)

16 pages, 2186 KiB

Open AccessArticle

A Chimeric Zika Virus between Viral Strains MR766 and BeH819015 Highlights a Role for E-glycan Loop in Antibody-mediated Virus Neutralization

by Etienne Frumence, Wildriss Viranaicken, Sandra Bos, Maria-Teresa Alvarez-Martinez, Marjolaine Roche, Jacques-Damien Arnaud, Gilles Gadea and Philippe Desprès

Vaccines 2019, 7(2), 55; https://doi.org/10.3390/vaccines7020055 - 24 Jun 2019

Cited by 15 | Viewed by 4088

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus which is of major public health concern. ZIKV infection is recognized as the cause of congenital Zika disease and other neurological defects, with no specific prophylactic or therapeutic treatments. As the humoral immune response is [...] Read more.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus which is of major public health concern. ZIKV infection is recognized as the cause of congenital Zika disease and other neurological defects, with no specific prophylactic or therapeutic treatments. As the humoral immune response is an essential component of protective immunity, there is an urgent need for effective vaccines that confer protection against ZIKV infection. In the present study, we evaluate the immunogenicity of chimeric viral clone ZIKBeHMR-2, in which the region encoding the structural proteins of the African strain MR766 backbone was replaced with its counterpart from the epidemic strain BeH819015. Three amino-acid substitutions I152T, T156I, and H158Y were introduced in the glycan loop of the E protein (E-GL) making ZIKBeHMR-2 a non-glycosylated virus. Adult BALB/c mice inoculated intraperitoneally with ZIKBeHMR-2 developed anti-ZIKV antibodies directed against viral proteins E and NS1 and a booster dose increased antibody titers. Immunization with ZIKBeHMR-2 resulted in a rapid production of neutralizing anti-ZIKV antibodies. Antibody-mediated ZIKV neutralization was effective against viral strain MR766, whereas epidemic ZIKV strains were poorly sensitive to neutralization by anti-ZIKBeHMR-2 immune sera. From our data, we propose that the three E-GL residues at positions E-152, E-156, and E-158 greatly influence the accessibility of neutralizing antibody epitopes on ZIKV. Full article

(This article belongs to the Special Issue Current Flavivirus Research Important for Vaccine Development )

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11 pages, 225 KiB

Open AccessReview

New Rabies Vaccines for Use in Humans

by Hildegund C. J. Ertl

Vaccines 2019, 7(2), 54; https://doi.org/10.3390/vaccines7020054 - 20 Jun 2019

Cited by 27 | Viewed by 10363

Abstract

Although vaccines are available, rabies still claims more than 55,000 human lives each year. In most cases, rabies vaccines are given to humans after their exposure to a rabid animal; pre-exposure vaccination is largely reserved for humans at high risk for contacts with [...] Read more.

Although vaccines are available, rabies still claims more than 55,000 human lives each year. In most cases, rabies vaccines are given to humans after their exposure to a rabid animal; pre-exposure vaccination is largely reserved for humans at high risk for contacts with the virus. Most cases of human rabies are transmitted by dogs. Dog rabies control by mass canine vaccination campaigns combined with intensive surveillance programs has led to a decline of human rabies in many countries but has been unsuccessful in others. Animal vaccination programs are also not suited to control human rabies caused by bat transmission, which is common in some Central American countries. Alternatively, or in addition, more widespread pre-exposure vaccination, especially in highly endemic remote areas, could be implemented. With the multiple dose regimens of current vaccines, pre-exposure vaccination is not cost effective for most countries and this warrants the development of new rabies vaccines, which are as safe as current vaccines, but achieve protective immunity after a single dose, and most importantly, are less costly. This chapter discusses novel rabies vaccines that are in late stage pre-clinical testing or have undergone clinical testing and their potential for replacing current vaccines. Full article

(This article belongs to the Special Issue New Horizons for Rabies Vaccines and Vaccination Strategies: Addressing 2030 Elimination Targets for Canine-mediated Rabies)

20 pages, 1576 KiB

Open AccessReview

Current and Novel Approaches in Influenza Management

by Erasmus Kotey, Deimante Lukosaityte, Osbourne Quaye, William Ampofo, Gordon Awandare and Munir Iqbal

Vaccines 2019, 7(2), 53; https://doi.org/10.3390/vaccines7020053 - 18 Jun 2019

Cited by 13 | Viewed by 7921

Abstract

Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic [...] Read more.

Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift. The efficacy of these vaccines is uncertain from year-to-year due to potential mismatch between the circulating viruses and vaccine strains, and mutations arising due to egg adaptation. Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome. Conventional vaccines also have variable efficacies for certain populations, including the young, old, and immunocompromised. This warrants for diverse efficacious vaccine developmental approaches, involving both active and passive immunization. As opposed to active immunization platforms (requiring the use of whole or portions of pathogens as vaccines), the rapidly developing passive immunization involves administration of either pathogen-specific or broadly acting antibodies against a kind or class of pathogens as a treatment to corresponding acute infection. Several antibodies with broadly acting capacities have been discovered that may serve as means to suppress influenza viral infection and allow the process of natural immunity to engage opsonized pathogens whilst boosting immune system by antibody-dependent mechanisms that bridge the innate and adaptive arms. By that; passive immunotherapeutics approach assumes a robust tool that could aid control of influenza viruses. In this review, we comment on some improvements in influenza management and promising vaccine development platforms with an emphasis on the protective capacity of passive immunotherapeutics especially when coupled with the use of antivirals in the management of influenza infection. Full article

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20 pages, 4271 KiB

Open AccessArticle

Covering Aluminum Oxide Nanoparticles with Biocompatible Materials to Efficiently Deliver Subunit Vaccines

by Ning Wang, Changlu Qiu, Minnan Chen, Ting Liu and Ting Wang

Vaccines 2019, 7(2), 52; https://doi.org/10.3390/vaccines7020052 - 17 Jun 2019

Cited by 11 | Viewed by 5144

Abstract

Subunit vaccines have advantages of good safety, minimal reactogenicity, and high specificity. However, subunit vaccines also show a crucial disadvantage of poor immunogenicity and, therefore, are often formulated with an adjuvant carrier to form a vaccine adjuvant-delivery system (VADS) to enhance their efficacies. [...] Read more.

Subunit vaccines have advantages of good safety, minimal reactogenicity, and high specificity. However, subunit vaccines also show a crucial disadvantage of poor immunogenicity and, therefore, are often formulated with an adjuvant carrier to form a vaccine adjuvant-delivery system (VADS) to enhance their efficacies. Alums, the coarse aggregates of the insoluble aluminum salts, are the conventional adjuvants and have been widely used in clinical vaccines for a long time. Unfortunately, alums also show two main drawbacks of low potency in eliciting cellular immunity, and high reactogenicity to cause unwanted inflammations. Therefore, herein the phospholipid bilayer-coated aluminum oxide nanoparticles (PLANs) and the PEGylated PLANs (PEG-PLANs) were engineered as a VADS to overcome the drawbacks of both subunit vaccines and coarse alums, while synergizing their functions. In vitro experiments demonstrated that, unlike the micron-sized alums, the nanosized PLANs and PEG-PLANs loaded with model antigen of ovalbumin (OVA) showed a high safety profile and were able to promote APC (antigen-presenting cell) uptake and engender lysosome escape for enhancing the MHC (major histocompatibility complex)-I-antigen display. Subcutaneously administered to mice, PLANs and, especially, PEG-PLANs smoothly trafficked into the draining lymph nodes, wherein the densely clustered immune cells were activated in substantial numbers, leading to robust immunoresponses and efficient production of the anti-antigen antibodies and CD8+ T cells. Thus, the aluminum-based nanocarriers, especially the PEG-PLANs, are a promising VADS possessing the potential of eliciting strong and comprehensive immunity against pathogens. Full article

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17 pages, 2526 KiB

Open AccessArticle

An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies

by Mohammad Amin Behzadi, Kathryn R. Stein, Maria Carolina Bermúdez-González, Viviana Simon, Raffael Nachbagauer and Domenico Tortorella

Vaccines 2019, 7(2), 51; https://doi.org/10.3390/vaccines7020051 - 14 Jun 2019

Viewed by 4776

Abstract

Human cytomegalovirus (CMV) is a highly prevalent pathogen with ~60%–90% seropositivity in adults. CMV can contribute to organ rejection in transplant recipients and is a major cause of birth defects in newborns. Currently, there are no approved vaccines against CMV. The epitope of [...] Read more.

Human cytomegalovirus (CMV) is a highly prevalent pathogen with ~60%–90% seropositivity in adults. CMV can contribute to organ rejection in transplant recipients and is a major cause of birth defects in newborns. Currently, there are no approved vaccines against CMV. The epitope of a CMV neutralizing monoclonal antibody against a conserved region of the envelope protein gH provided the basis for a new CMV vaccine design. We exploited the influenza A virus as a vaccine platform due to the highly immunogenic head domain of its hemagglutinin envelope protein. Influenza A variants were engineered by reverse genetics to express the epitope of an anti-CMV gH neutralizing antibody that recognizes native gH into the hemagglutinin antigenic Sa site. We determined that the recombinant influenza variants expressing 7, 10, or 13 residues of the anti-gH neutralizing antibody epitope were recognized and neutralized by the anti-gH antibody 10C10. Mice vaccinated with the influenza/CMV chimeric viruses induced CMV-specific antibodies that recognized the native gH protein and inhibited virus infection. In fact, the influenza variants expressing 7–13 gH residues neutralized a CMV infection at ~60% following two immunizations with variants expressing the 13 residue gH peptide produced the highest levels of neutralization. Collectively, our study demonstrates that a variant influenza virus inserted with a gH peptide can generate a humoral response that limits a CMV infection. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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12 pages, 1812 KiB

Open AccessReview

Use of a Novel Enhanced DNA Vaccine Vector for Preclinical Virus Vaccine Investigation

by Rosamund Chapman and Edward P. Rybicki

Vaccines 2019, 7(2), 50; https://doi.org/10.3390/vaccines7020050 - 13 Jun 2019

Cited by 12 | Viewed by 4412

Abstract

DNA vaccines are stable, safe, and cost effective to produce and relatively quick and easy to manufacture. However, to date, DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to [...] Read more.

DNA vaccines are stable, safe, and cost effective to produce and relatively quick and easy to manufacture. However, to date, DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172 bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits, and macaques at 4–10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome. Full article

(This article belongs to the Special Issue Advances in DNA Vaccines)

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9 pages, 978 KiB

Open AccessBrief Report

Increased Immunogenicity of Full-Length Protein Antigens through Sortase-Mediated Coupling on the PapMV Vaccine Platform

by Marie-Ève Laliberté-Gagné, Marilène Bolduc, Ariane Thérien, Caroline Garneau, Philippe Casault, Pierre Savard, Jérome Estaquier and Denis Leclerc

Vaccines 2019, 7(2), 49; https://doi.org/10.3390/vaccines7020049 - 12 Jun 2019

Cited by 16 | Viewed by 3238

Abstract

Background: Flexuous rod-shape nanoparticles—made of the coat protein of papaya mosaic virus (PapMV)—provide a promising vaccine platform for the presentation of viral antigens to immune cells. The PapMV nanoparticles can be combined with viral antigens or covalently linked to them. The coupling [...] Read more.

Background: Flexuous rod-shape nanoparticles—made of the coat protein of papaya mosaic virus (PapMV)—provide a promising vaccine platform for the presentation of viral antigens to immune cells. The PapMV nanoparticles can be combined with viral antigens or covalently linked to them. The coupling to PapMV was shown to improve the immune response triggered against peptide antigens (<39 amino acids) but it remains to be tested if large proteins can be coupled to this platform and if the coupling will lead to an immune response improvement. Methods: Two full-length recombinant viral proteins, the influenza nucleoprotein (NP) and the simian immunodeficiency virus group-specific protein antigen (GAG) were coupled to PapMV nanoparticles using sortase A. Mice were immunized with the nanoparticles coupled to the antigens and the immune response directed to the antigens were analyzed by ELISA and ELISPOT. Results: We showed the feasibility of coupling two different full-length proteins (GAG and NP) to the nanoparticle. We also showed that the coupling to PapMV nanoparticles improved significantly the humoral and the cytotoxic T lymphocyte (CTL) immune response to the antigens. Conclusion: This proof of concept demonstrates the versatility and the efficacy of the PapMV vaccine platform in the design of vaccines against viral diseases. Full article

(This article belongs to the Section Vaccines against Infectious Diseases)

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12 pages, 263 KiB

Open AccessArticle

Childhood Immunization in Ethiopia: Accuracy of Maternal Recall Compared to Vaccination Cards

by Julia M. Porth, Abram L. Wagner, Yemesrach A. Tefera and Matthew L. Boulton

Vaccines 2019, 7(2), 48; https://doi.org/10.3390/vaccines7020048 - 07 Jun 2019

Cited by 23 | Viewed by 3189

Abstract

Health surveys conducted in low- and middle-income countries typically estimate childhood vaccination status based on written vaccination cards, maternal recall (when cards are not available), or a combination of both. This analysis aimed to assess the accuracy of maternal recall of a child’s [...] Read more.

Health surveys conducted in low- and middle-income countries typically estimate childhood vaccination status based on written vaccination cards, maternal recall (when cards are not available), or a combination of both. This analysis aimed to assess the accuracy of maternal recall of a child’s vaccination status in Ethiopia. Data came from a 2016 cross-sectional study conducted in the Southern Nations, Nationalities, and Peoples’ (SNNP) Region of Ethiopia. Vaccine doses received by a given 12–23-month-old child were recorded from both a vaccination card and based on maternal recall and then compared. Concordance, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen’s Kappa were calculated. Estimates of full immunization coverage were similar when collected via vaccination card (75%) and maternal recall (74%). For fully vaccinated children, comparison of maternal recall versus vaccination card showed high concordance (96%), sensitivity (97%), specificity (93%), PPV (98%), NPV (92%), and Kappa (90%). Accuracy of maternal recall of a child’s vaccination status is high in the SNNP region of Ethiopia. Although determination of vaccination status via vaccination card is preferred since it constitutes a written record, maternal recall can also be used with confidence when vaccination cards are not available. Full article

13 pages, 2690 KiB

Open AccessArticle

Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design

by Ariane C. Gomes, E. S. Roesti, Aadil El-Turabi and Martin F. Bachmann

Vaccines 2019, 7(2), 47; https://doi.org/10.3390/vaccines7020047 - 04 Jun 2019

Cited by 37 | Viewed by 4930

Abstract

Nucleic acid packed within virus-like particles (VLPs) is shown to shape the immune response and to induce stronger B cell responses in different immunisation models. Here, using a VLP displaying the highly conserved extracellular domain of the M2 protein (M2e) from the influenza [...] Read more.

Nucleic acid packed within virus-like particles (VLPs) is shown to shape the immune response and to induce stronger B cell responses in different immunisation models. Here, using a VLP displaying the highly conserved extracellular domain of the M2 protein (M2e) from the influenza viruses as an antigen, we demonstrate that the type of RNA packaged into VLPs can alter the quality of the induced humoral response. By comparing prokaryotic RNA (pRNA), eukaryotic RNA (eRNA) and transfer RNA (tRNA), we find that pRNA induces the most protective IgG subclasses using a murine influenza model. We provide evidence that this process is predominantly dependent on endosomal Toll-like receptor (TLR7), and rule out a role for cytoplasmic mitochondrial antiviral signalling protein (MAVS) and its upstream retinoic acid-inducible gene-I-like receptors (RIG-I). Our findings provide considerations for the rational design of VLP-based vaccines and the immunomodulation exerted by TLR7 ligands packaged within the particles. Based on this work, we conclude that VLPs packing prokaryotic RNA must be preferred whenever a response dominated by IgG2 is desired, while eukaryotic RNA should be employed in order to induce a response dominated by IgG1. Full article

(This article belongs to the Section Influenza Virus Vaccines)

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13 pages, 1415 KiB

Open AccessArticle

Bacterial Outer Membrane Vesicles (OMVs)-Based Dual Vaccine for Influenza A H1N1 Virus and MERS-CoV

by Mahmoud M. Shehata, Ahmed Mostafa, Lisa Teubner, Sara H. Mahmoud, Ahmed Kandeil, Rabeh Elshesheny, Thamer A. Boubak, Renate Frantz, Luigi La Pietra, Stephan Pleschka, Ahmed Osman, Ghazi Kayali, Trinad Chakraborty, Mohamed A. Ali and Mobarak Abu Mraheil

Vaccines 2019, 7(2), 46; https://doi.org/10.3390/vaccines7020046 - 28 May 2019

Cited by 38 | Viewed by 6723

Abstract

Vaccination is the most functional medical intervention to prophylactically control severe diseases caused by human-to-human or animal-to-human transmissible viral pathogens. Annually, seasonal influenza epidemics attack human populations leading to 290–650 thousand deaths/year worldwide. Recently, a novel Middle East Respiratory Syndrome Coronavirus emerged. Together, [...] Read more.

Vaccination is the most functional medical intervention to prophylactically control severe diseases caused by human-to-human or animal-to-human transmissible viral pathogens. Annually, seasonal influenza epidemics attack human populations leading to 290–650 thousand deaths/year worldwide. Recently, a novel Middle East Respiratory Syndrome Coronavirus emerged. Together, those two viruses present a significant public health burden in areas where they circulate. Herein, we generated a bacterial outer membrane vesicles (OMVs)-based vaccine presenting the antigenic stable chimeric fusion protein of the H1-type haemagglutinin (HA) of the pandemic influenza A virus (H1N1) strain from 2009 (H1N1pdm09) and the receptor binding domain (RBD) of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (OMVs-H1/RBD). Our results showed that the chimeric antigen could induce specific neutralizing antibodies against both strains leading to protection of immunized mice against H1N1pdm09 and efficient neutralization of MERS-CoV. This study demonstrate that OMVs-based vaccines presenting viral antigens provide a safe and reliable approach to protect against two different viral infections. Full article

(This article belongs to the Section Influenza Virus Vaccines)

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23 pages, 758 KiB

Open AccessReview

Computational Approaches and Challenges to Developing Universal Influenza Vaccines

by Xueting Qiu, Venkata R. Duvvuri and Justin Bahl

Vaccines 2019, 7(2), 45; https://doi.org/10.3390/vaccines7020045 - 28 May 2019

Cited by 12 | Viewed by 6667

Abstract

The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate [...] Read more.

The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines. Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale. This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes. Interactions between virus-host-environment determine the evolvability of the influenza population. We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine. Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection. Full article

(This article belongs to the Special Issue The Future of Influenza Virus Vaccines—Perspectives from the young investigators' point of view)

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16 pages, 2311 KiB

Open AccessArticle

Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein–Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth

by Krzysztof Wojtak, Alfredo Perales-Puchalt and David B. Weiner

Vaccines 2019, 7(2), 44; https://doi.org/10.3390/vaccines7020044 - 24 May 2019

Cited by 12 | Viewed by 4376

Abstract

Infectious diseases are linked to 15%–20% of cancers worldwide. Among them, Epstein–Barr virus (EBV) is an oncogenic herpesvirus that chronically infects over 90% of the adult population, with over 200,000 cases of cancer and 150,000 cancer-related deaths attributed to it yearly. Acute EBV [...] Read more.

Infectious diseases are linked to 15%–20% of cancers worldwide. Among them, Epstein–Barr virus (EBV) is an oncogenic herpesvirus that chronically infects over 90% of the adult population, with over 200,000 cases of cancer and 150,000 cancer-related deaths attributed to it yearly. Acute EBV infection can present as infectious mononucleosis, and lead to the future onset of multiple cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Many of these cancers express latent viral genes, including Epstein–Barr virus nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2). Previous attempts to create potent immunogens against EBV have been reported but generated mixed success. We designed novel Synthetic Consensus (SynCon) DNA vaccines against EBNA1, LMP1 and LMP2 to improve on the immune potency targeting important antigens expressed in latently infected cells. These EBV tumor antigens are hypothesized to be useful targets for potential immunotherapy of EBV-driven cancers. We optimized the genetic sequences for these three antigens, studied them for expression, and examined their immune profiles in vivo. We observed that these immunogens generated unique profiles based on which antigen was delivered as the vaccine target. EBNA1vax and LMP2Avax generated the most robust T cell immunity. Interestingly, LMP1vax was a very weak immunogen, generating very low levels of CD8 T cell immunity both as a standalone vaccine and as part of a trivalent vaccine cocktail. LMP2Avax was able to drive immunity that impacted EBV-antigen-positive tumor growth. These studies suggest that engineered EBV latent protein vaccines deserve additional study as potential agents for immunotherapy of EBV-driven cancers. Full article

(This article belongs to the Special Issue Advances in DNA Vaccines)

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13 pages, 1973 KiB

Open AccessArticle

Evaluation of a Recombinant Mouse X Pig Chimeric Anti-Porcine DEC205 Antibody Fused with Structural and Nonstructural Peptides of PRRS Virus

by Lorena Bustamante-Córdova, Mónica Reséndiz-Sandoval and Jesús Hernández

Vaccines 2019, 7(2), 43; https://doi.org/10.3390/vaccines7020043 - 23 May 2019

Cited by 7 | Viewed by 3933

Abstract

Activation of the immune system using antigen targeting to the dendritic cell receptor DEC205 presents great potential in the field of vaccination. The objective of this work was to evaluate the immunogenicity and protectiveness of a recombinant mouse x pig chimeric antibody fused [...] Read more.

Activation of the immune system using antigen targeting to the dendritic cell receptor DEC205 presents great potential in the field of vaccination. The objective of this work was to evaluate the immunogenicity and protectiveness of a recombinant mouse x pig chimeric antibody fused with peptides of structural and nonstructural proteins of porcine respiratory and reproductive syndrome virus (PRRSV) directed to DEC205⁺ cells. Priming and booster immunizations were performed three weeks apart and administered intradermally in the neck area. All pigs were challenged with PRRSV two weeks after the booster immunization. Immunogenicity was evaluated by assessing the presence of antibodies anti-PRRSV, the response of IFN-γ-producing CD4⁺ cells, and the proliferation of cells. Protection was determined by assessing the viral load in the blood, lungs, and tonsils using qRT-PCR. The results showed that the vaccine exhibited immunogenicity but conferred limited protection. The vaccine group had a lower viral load in the tonsils and a significantly higher production of antibodies anti-PRRSV than the control group (p < 0.05); the vaccine group also produced more CD4⁺IFN-γ⁺ cells in response to peptides from the M and Nsp2 proteins. In conclusion, this antigenized recombinant mouse x pig chimeric antibody had immunogenic properties that could be enhanced to improve the level of protection and vaccine efficiency. Full article

(This article belongs to the Section Veterinary Vaccines)

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22 pages, 2767 KiB

Open AccessArticle

Designed DNA-Encoded IL-36 Gamma Acts as a Potent Molecular Adjuvant Enhancing Zika Synthetic DNA Vaccine-Induced Immunity and Protection in a Lethal Challenge Model

by Lumena Louis, Megan C. Wise, Hyeree Choi, Daniel O. Villarreal, Kar Muthumani and David B. Weiner

Vaccines 2019, 7(2), 42; https://doi.org/10.3390/vaccines7020042 - 22 May 2019

Cited by 10 | Viewed by 4427

Abstract

Identification of novel molecular adjuvants which can boost and enhance vaccine-mediated immunity and provide dose-sparing potential against complex infectious diseases and for immunotherapy in cancer is likely to play a critical role in the next generation of vaccines. Given the number of challenging [...] Read more.

Identification of novel molecular adjuvants which can boost and enhance vaccine-mediated immunity and provide dose-sparing potential against complex infectious diseases and for immunotherapy in cancer is likely to play a critical role in the next generation of vaccines. Given the number of challenging targets for which no or only partial vaccine options exist, adjuvants that can address some of these concerns are in high demand. Here, we report that a designed truncated Interleukin-36 gamma (IL-36 gamma) encoded plasmid can act as a potent adjuvant for several DNA-encoded vaccine targets including human immunodeficiency virus (HIV), influenza, and Zika in immunization models. We further show that the truncated IL-36 gamma (opt-36γt) plasmid provides improved dose sparing as it boosts immunity to a suboptimal dose of a Zika DNA vaccine, resulting in potent protection against a lethal Zika challenge. Full article

(This article belongs to the Special Issue Advances in DNA Vaccines)

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19 pages, 2063 KiB

Open AccessArticle

A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model

by Lisa Nika, Sara Cuadrado-Castano, Guha Asthagiri Arunkumar, Clemens Grünwald-Gruber, Meagan McMahon, Krisztina Koczka, Adolfo García-Sastre, Florian Krammer and Reingard Grabherr

Vaccines 2019, 7(2), 41; https://doi.org/10.3390/vaccines7020041 - 20 May 2019

Cited by 9 | Viewed by 4845

Abstract

Human epidermal growth factor receptor-2 (HER2) is upregulated in 20% to 30% of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable [...] Read more.

Human epidermal growth factor receptor-2 (HER2) is upregulated in 20% to 30% of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable tumor-specific immune responses have become an attractive research area. Recently, we have shown that budded virus-like particles (VLPs) produced in Sf9 insect cells are an ideal platform for the expression of complex membrane proteins. To assess the efficacy of antigen-displaying VLPs as active cancer vaccines, BALB/c mice were immunized with insect cell glycosylated and mammalian-like glycosylated HER2-displaying VLPs in combination with two different adjuvants and were challenged with HER2-positive tumors. Higher HER2-specific antibody titers and effector functions were induced in mice vaccinated with insect cell glycosylated HER2 VLPs compared to mammalian-like glycosylated counterparts. Moreover, insect cell glycosylated HER2 VLPs elicited a protective effect in mice grafted with HER2-positive mammary carcinoma cells. Interestingly, no protection was observed in mice that were adjuvanted with Poly (I:C). Here, we show that antigen-displaying VLPs produced in Sf9 insect cells were able to induce robust and durable immune responses in vivo and have the potential to be utilized as active cancer vaccines. Full article

(This article belongs to the Section Cancer Vaccines and Immunotherapy)

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12 pages, 1802 KiB

Open AccessArticle

Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine

by Pedro M. Folegatti, Duncan Bellamy, Rachel Roberts, Jonathan Powlson, Nick J. Edwards, Catherine F. Mair, Georgina Bowyer, Ian Poulton, Celia H. Mitton, Nicky Green, Eleanor Berrie, Alison M. Lawrie, Adrian V.S. Hill, Katie J. Ewer, John Hermon-Taylor and Sarah C. Gilbert

Vaccines 2019, 7(2), 40; https://doi.org/10.3390/vaccines7020040 - 15 May 2019

Cited by 20 | Viewed by 7341

Abstract

Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens. Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising [...] Read more.

Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens. Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising antibodies. We have constructed a replication deficient simian adenovirus-vectored vaccine (ChAdOx2) expressing 4 genes from the Mycobacterium avium subspecies paratuberculosis (AhpC, Gsd, p12 and mpa). Safety and T-cell immunogenicity results of the first clinical use of the ChAdOx2 vector are presented here. The trial was conducted using a ‘three-plus-three’ dose escalation study design. We demonstrate the vaccine is safe, well tolerated and immunogenic. Full article

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13 pages, 1219 KiB

Open AccessArticle

Combating Vaccine Hesitancy with Vaccine-Preventable Disease Familiarization: An Interview and Curriculum Intervention for College Students

by Deborah K. Johnson, Emily J. Mello, Trent D. Walker, Spencer J. Hood, Jamie L. Jensen and Brian D. Poole

Vaccines 2019, 7(2), 39; https://doi.org/10.3390/vaccines7020039 - 12 May 2019

Cited by 25 | Viewed by 27238

Abstract

In 2019, the World Health Organization (WHO) listed vaccine hesitancy in its top ten threats to global health. Vaccine hesitancy is a “delay in acceptance or refusal to vaccinate despite availability of vaccination services”. Urban areas with large amounts of vaccine hesitancy are [...] Read more.

In 2019, the World Health Organization (WHO) listed vaccine hesitancy in its top ten threats to global health. Vaccine hesitancy is a “delay in acceptance or refusal to vaccinate despite availability of vaccination services”. Urban areas with large amounts of vaccine hesitancy are at risk for the resurgence of vaccine-preventable diseases (VPDs). Many vaccine-hesitant (VH) parents may be unfamiliar with the consequences of VPDs, and thus might be swayed when confronted with the symptoms and dangers of VPDs. As such, we sought to educate college students (future parents) in an urban vaccine-hesitant hotspot by assigning them to interview family or community members who had experienced a VPD. Student vaccine attitudes were assessed by surveys before and after the interviews. Vaccine-hesitant students who conducted a VPD interview but received no additional vaccine educational materials were significantly more likely (interaction term p < 0.001) to become pro-vaccine (PV) (68%) than students who conducted an autoimmune interview and received no additional educational materials. Additionally, students whose interviewees experienced intense physical suffering or physical limitations or students who were enrolled in a course with intensive VPD and vaccine curriculum had significantly increased vaccine attitudes. This suggests that introducing students to VPDs can decrease vaccine hesitancy. Full article

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14 pages, 1679 KiB

Open AccessReview

Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines

by Ashish C. Shrestha, Danushka K. Wijesundara, Makutiro G. Masavuli, Zelalem A. Mekonnen, Eric J. Gowans and Branka Grubor-Bauk

Vaccines 2019, 7(2), 38; https://doi.org/10.3390/vaccines7020038 - 30 Apr 2019

Cited by 11 | Viewed by 4730

Abstract

DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA [...] Read more.

DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity. In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin. The application of this innovative DNA technology has considerable potential in the development of effective vaccines. Full article

(This article belongs to the Special Issue Advances in DNA Vaccines)

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20 pages, 318 KiB

Open AccessReview

A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

by Margaret A. Liu

Vaccines 2019, 7(2), 37; https://doi.org/10.3390/vaccines7020037 - 24 Apr 2019

Cited by 275 | Viewed by 75105

Abstract

This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary [...] Read more.

This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials. Full article

(This article belongs to the Special Issue Advances in DNA Vaccines)

11 pages, 561 KiB

Open AccessArticle

New Promising Targets for Synthetic Omptin-Based Peptide Vaccine against Gram-Negative Pathogens

by Valentina A. Feodorova, Anna M. Lyapina, Sergey S. Zaitsev, Maria A. Khizhnyakova, Lidiya V. Sayapina, Onega V. Ulianova, Sergey S. Ulyanov and Vladimir L. Motin

Vaccines 2019, 7(2), 36; https://doi.org/10.3390/vaccines7020036 - 10 Apr 2019

Cited by 5 | Viewed by 3629

Abstract

Omptins represent a family of proteases commonly found in various Gram-negative pathogens. These proteins play an important role in host–pathogen interaction and have been recognized as key virulence factors, highlighting the possibility of developing an omptin-based broad-spectrum vaccine. The prototypical omptin, His-tagged recombinant [...] Read more.

Omptins represent a family of proteases commonly found in various Gram-negative pathogens. These proteins play an important role in host–pathogen interaction and have been recognized as key virulence factors, highlighting the possibility of developing an omptin-based broad-spectrum vaccine. The prototypical omptin, His-tagged recombinant Pla, was used as a model target antigen. In total, 46 linear and 24 conformational epitopes for the omptin family were predicted by the use of ElliPro service. Among these we selected highly conserved, antigenic, non-allergenic, and immunogenic B-cell epitopes. Five epitopes (2, 6, 8, 10, and 11 corresponding to Pla regions 52–60, 146–150, 231–234, 286–295, and 306–311, respectively) could be the first choice for the development of the new generation of target-peptide-based vaccine against plague. The partial residues of omptin epitopes 6, 8, and 10 (regions 136–145, 227–230, and 274–285) could be promising targets for the multi-pathogen vaccine against a group of enterobacterial infections. The comparative analysis and 3D modeling of amino acid sequences of several omptin family proteases, such as Pla (Yersinia pestis), PgtE (Salmonella enterica), SopA (Shigella flexneri), OmpT, and OmpP (Escherichia coli), confirmed their high cross-homology with respect to the identified epitope clusters and possible involvement of individual epitopes in host–pathogen interaction. Full article

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11 pages, 1214 KiB

Open AccessMeeting Report

20th International Conference on Emerging Infectious Diseases in the Pacific Rim Organized by the United States-Japan Cooperative Medical Sciences Program (USJCMSP)

by USJCMSP AIDS, ARI, Cancer, Hepatitis, Immunology and Viral Diseases Panels, K. Gayle Bernabe, Kristina T. Lu, F. Gray Handley, Diane E. Griffin, Ichiro Kurane, Aikichi Iwamoto, George F. Gao and Florian Krammer

Vaccines 2019, 7(2), 35; https://doi.org/10.3390/vaccines7020035 - 02 Apr 2019

Cited by 1 | Viewed by 4053

Abstract

The 20th International Conference on Emerging Infectious Diseases in the Pacific Rim to3ok place in Shenzhen, China on January 8–9, 2018 followed by meetings of the acquired immunodeficiency syndrome (AIDS)/immunology, acute respiratory infections, cancer, hepatitis, and viral diseases panels on January 10–11. The [...] Read more.

The 20th International Conference on Emerging Infectious Diseases in the Pacific Rim to3ok place in Shenzhen, China on January 8–9, 2018 followed by meetings of the acquired immunodeficiency syndrome (AIDS)/immunology, acute respiratory infections, cancer, hepatitis, and viral diseases panels on January 10–11. The conference was organized as part of the United States-Japan Cooperative Medical Sciences Program (USJCMSP) by the Japan Agency for Medical Research and Development (AMED) and the U.S. National Institutes of Health (NIH) and was locally hosted by the Shenzhen Third People’s Hospital and the Chinese Academy of Sciences (CAS) Institute of Microbiology. The conference provides the basis for networking and fostering of collaboration opportunities between researchers in Southeast Asia and the United States based on the scientific and interactive platform of the USJCMSP and takes place in the region on an annual basis. This report summarizes the discussions and conclusions from the conference. Full article

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15 pages, 1663 KiB

Open AccessArticle

In silico Designed Ebola Virus T-Cell Multi-Epitope DNA Vaccine Constructions Are Immunogenic in Mice

by Sergei I. Bazhan, Denis V. Antonets, Larisa I. Karpenko, Svetlana F. Oreshkova, Olga N. Kaplina, Ekaterina V. Starostina, Sergei G. Dudko, Sofia A. Fedotova and Alexander A. Ilyichev

Vaccines 2019, 7(2), 34; https://doi.org/10.3390/vaccines7020034 - 29 Mar 2019

Cited by 47 | Viewed by 6349

Abstract

Background: The lack of effective vaccines against Ebola virus initiates a search for new approaches to overcoming this problem. The aim of the study was to design artificial polyepitope T-cell immunogens—candidate DNA vaccines against Ebola virus and to evaluate their capacity to [...] Read more.

Background: The lack of effective vaccines against Ebola virus initiates a search for new approaches to overcoming this problem. The aim of the study was to design artificial polyepitope T-cell immunogens—candidate DNA vaccines against Ebola virus and to evaluate their capacity to induce a specific immune response in a laboratory animal model. Method: Design of two artificial polyepitope T-cell immunogens, one of which (EV.CTL) includes cytotoxic and the other (EV.Th)—T-helper epitopes of Ebola virus proteins was carried out using original TEpredict/PolyCTLDesigner software. Synthesized genes were cloned in pcDNA3.1 plasmid vector. Target gene expression was estimated by synthesis of specific mRNAs and proteins in cells transfected with recombinant plasmids. Immunogenicity of obtained DNA vaccine constructs was evaluated according to their capacity to induce T-cell response in BALB/c mice using IFN ELISpot and ICS. Results: We show that recombinant plasmids pEV.CTL and pEV.Th encoding artificial antigens provide synthesis of corresponding mRNAs and proteins in transfected cells, as well as induce specific responses both to CD4+ and CD8+ T-lymphocytes in immunized animals. Conclusions: The obtained recombinant plasmids can be regarded as promising DNA vaccine candidates in future studies of their capacity to induce cytotoxic and protective responses against Ebola virus. Full article

(This article belongs to the Special Issue Advances in DNA Vaccines)

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Vaccines, Volume 7, Issue 2 (June 2019) – 23 articles

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