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1173 KiB

Open AccessArticle

Efficient Strategy to Generate a Vectored Duck Enteritis Virus Delivering Envelope of Duck Tembusu Virus

by Zhong Zou, Zhigang Liu and Meilin Jin

Viruses 2014, 6(6), 2428-2443; https://doi.org/10.3390/v6062428 - 20 Jun 2014

Cited by 27 | Viewed by 8037

Abstract

Duck Tembusu virus (DTMUV) is a recently emerging pathogenic flavivirus that has resulted in a huge economic loss in the duck industry. However, no vaccine is currently available to control this pathogen. Consequently, a practical strategy to construct a vaccine against this pathogen [...] Read more.

Duck Tembusu virus (DTMUV) is a recently emerging pathogenic flavivirus that has resulted in a huge economic loss in the duck industry. However, no vaccine is currently available to control this pathogen. Consequently, a practical strategy to construct a vaccine against this pathogen should be determined. In this study, duck enteritis virus (DEV) was examined as a candidate vaccine vector to deliver the envelope (E) of DTMUV. A modified mini-F vector was inserted into the SORF3 and US2 gene junctions of the attenuated DEV vaccine strain C-KCE genome to generate an infectious bacterial artificial chromosome (BAC) of C-KCE (vBAC-C-KCE). The envelope (E) gene of DTMUV was inserted into the C-KCE genome through the mating-assisted genetically integrated cloning (MAGIC) strategy, resulting in the recombinant vector, pBAC-C-KCE-E. A bivalent vaccine C-KCE-E was generated by eliminating the BAC backbone. Immunofluorescence and western blot analysis results indicated that the E proteins were vigorously expressed in C-KCE-E-infected chicken embryo fibroblasts (CEFs). Duck experiments demonstrated that the insertion of the E gene did not alter the protective efficacy of C-KCE. Moreover, C-KCE-E-immunized ducks induced neutralization antibodies against DTMUV. These results demonstrated, for the first time, that recombinant C-KCE-E can serve as a potential bivalent vaccine against DEV and DTMUV. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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2766 KiB

Open AccessArticle

Infection with Non-Lethal West Nile Virus Eg101 Strain Induces Immunity that Protects Mice against the Lethal West Nile Virus NY99 Strain

by Mukesh Kumar, Maile O'Connell, Madhuri Namekar and Vivek R. Nerurkar

Viruses 2014, 6(6), 2328-2339; https://doi.org/10.3390/v6062328 - 6 Jun 2014

Cited by 16 | Viewed by 7523

Abstract

Herein we demonstrate that infection of mice with West Nile virus (WNV) Eg101 provides protective immunity against lethal challenge with WNV NY99. Our data demonstrated that WNV Eg101 is largely non-virulent in adult mice when compared to WNV NY99. By day 6 after [...] Read more.

Herein we demonstrate that infection of mice with West Nile virus (WNV) Eg101 provides protective immunity against lethal challenge with WNV NY99. Our data demonstrated that WNV Eg101 is largely non-virulent in adult mice when compared to WNV NY99. By day 6 after infection, WNV-specific IgM and IgG antibodies, and neutralizing antibodies were detected in the serum of all WNV Eg101 infected mice. Plaque reduction neutralization test data demonstrated that serum from WNV Eg101 infected mice neutralized WNV Eg101 and WNV NY99 strains with similar efficiency. Three weeks after infection, WNV Eg101 immunized mice were challenged subcutaneously or intracranially with lethal dose of WNV NY99 and observed for additional three weeks. All the challenged mice were protected against disease and no morbidity and mortality was observed in any mice. In conclusion, our data for the first time demonstrate that infection of mice with WNV Eg101 induced high titers of WNV specific IgM and IgG antibodies, and cross-reactive neutralizing antibodies, and the resulting immunity protected all immunized animals from both subcutaneous and intracranial challenge with WNV NY99. These observations suggest that WNV Eg101 may be a suitable strain for the development of a vaccine in humans against virulent strains of WNV. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessArticle

Anti-Tumor Effects of an Oncolytic Adenovirus Expressing Hemagglutinin-Neuraminidase of Newcastle Disease Virus in Vitro and in Vivo

by Dongyun He, Lili Sun, Chang Li, Ningning Hu, Yuan Sheng, Zhifei Chen, Xiao Li, Baorong Chi and Ningyi Jin

Viruses 2014, 6(2), 856-874; https://doi.org/10.3390/v6020856 - 18 Feb 2014

Cited by 17 | Viewed by 7594

Abstract

Oncolytic virotherapy has been an attractive drug platform for targeted therapy of cancer over the past few years. Viral vectors can be used to target and lyse cancer cells, but achieving good efficacy and specificity with this treatment approach is a major challenge. [...] Read more.

Oncolytic virotherapy has been an attractive drug platform for targeted therapy of cancer over the past few years. Viral vectors can be used to target and lyse cancer cells, but achieving good efficacy and specificity with this treatment approach is a major challenge. Here, we assessed the ability of a novel dual-specific anti-tumor oncolytic adenovirus, expressing the hemagglutinin-neuraminidase (HN) gene from the Newcastle disease virus under the human telomerase reverse transcriptase (hTERT) promoter (Ad-hTERTp-E1a-HN), to inhibit esophageal cancer EC-109 cells in culture and to reduce tumor burden in xenografted BALB/c nude mice. In vitro, infection with Ad-hTERT-E1a-HN could inhibit the growth of EC-109 cells significantly and also protect normal human liver cell line L02 from growth suppression in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Ad-hTERT-E1a-HN also effectively and selectively decreased the sialic acid level on EC-109 cells, but not on L02 cells. Furthermore, Ad-hTERT-E1a-HN was shown to induce the apoptosis pathway via acridine orange and ethidium bromide staining (AO/EB staining), increase reactive oxygen species (ROS), reduce mitochondrial membrane potential and release cytochrome c. In vivo, xenografted BALB/c nude mice were treated via intratumoral or intravenous injections of Ad-hTERT-E1a-HN. Although both treatments showed an obvious suppression in tumor volume, only Ad-hTERT-E1a-HN delivered via intratumoral injection elicited a complete response to treatment. These results reinforced previous findings and highlighted the potential therapeutic application of Ad-hTERT-E1a-HN for treatment of esophageal cancer in clinical trials. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Review

Jump to: Research

726 KiB

Open AccessReview

Options and Obstacles for Designing a Universal Influenza Vaccine

by Yo Han Jang and Baik Lin Seong

Viruses 2014, 6(8), 3159-3180; https://doi.org/10.3390/v6083159 - 18 Aug 2014

Cited by 40 | Viewed by 11412

Abstract

Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this [...] Read more.

Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this goal, a prime/boost immunization strategy has been heralded to redirect host immune responses from the variable globular head domain to the conserved stalk domain of HA. While this approach has been successful in eliciting cross-reactive antibodies against the HA stalk domain, protective efficacy remains relatively poor due to the low immunogenicity of the domain, and the cross-reactivity was only within the same group, rather than among different groups. Additionally, concerns are raised on the possibility of vaccine-associated enhancement of viral infection and whether multiple boost immunization protocols would be considered practical from a clinical standpoint. Live attenuated vaccine hitherto remains unexplored, but is expected to serve as an alternative approach, considering its superior cross-reactivity. This review summarizes recent advancements in the HA stalk-based universal influenza vaccines, discusses the pros and cons of these approaches with respect to the potentially beneficial and harmful effects of neutralizing and non-neutralizing antibodies, and suggests future guidelines towards the design of a truly protective universal influenza vaccine. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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564 KiB

Open AccessReview

Virus-Vectored Influenza Virus Vaccines

by Ralph A. Tripp and S. Mark Tompkins

Viruses 2014, 6(8), 3055-3079; https://doi.org/10.3390/v6083055 - 7 Aug 2014

Cited by 40 | Viewed by 9758

Abstract

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines [...] Read more.

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases

by Arwen F. Altenburg, Joost H. C. M. Kreijtz, Rory D. De Vries, Fei Song, Robert Fux, Guus F. Rimmelzwaan, Gerd Sutter and Asisa Volz

Viruses 2014, 6(7), 2735-2761; https://doi.org/10.3390/v6072735 - 17 Jul 2014

Cited by 97 | Viewed by 22876

Abstract

Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have [...] Read more.

Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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760 KiB

Open AccessReview

RNA Virus Reverse Genetics and Vaccine Design

by Christopher C. Stobart and Martin L. Moore

Viruses 2014, 6(7), 2531-2550; https://doi.org/10.3390/v6072531 - 25 Jun 2014

Cited by 83 | Viewed by 15228

Abstract

RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine [...] Read more.

RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

In the Shadow of Hemagglutinin: A Growing Interest in Influenza Viral Neuraminidase and Its Role as a Vaccine Antigen

by Teddy John Wohlbold and Florian Krammer

Viruses 2014, 6(6), 2465-2494; https://doi.org/10.3390/v6062465 - 23 Jun 2014

Cited by 134 | Viewed by 21865

Abstract

Despite the availability of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to have a significant, annual impact on the morbidity and mortality of human beings, highlighting the continued need for research in the field. Current vaccine strategies predominantly focus on raising [...] Read more.

Despite the availability of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to have a significant, annual impact on the morbidity and mortality of human beings, highlighting the continued need for research in the field. Current vaccine strategies predominantly focus on raising a humoral response against hemagglutinin (HA)—the more abundant, immunodominant glycoprotein on the surface of the influenza virus. In fact, anti-HA antibodies are often neutralizing, and are used routinely to assess vaccine immunogenicity. Neuraminidase (NA), the other major glycoprotein on the surface of the influenza virus, has historically served as the target for antiviral drug therapy and is much less studied in the context of humoral immunity. Yet, the quest to discern the exact importance of NA-based protection is decades old. Also, while antibodies against the NA glycoprotein fail to prevent infection of the influenza virus, anti-NA immunity has been shown to lessen the severity of disease, decrease viral lung titers in animal models, and reduce viral shedding. Growing evidence is intimating the possible gains of including the NA antigen in vaccine design, such as expanded strain coverage and increased overall immunogenicity of the vaccine. After giving a tour of general influenza virology, this review aims to discuss the influenza A virus neuraminidase while focusing on both the historical and present literature on the use of NA as a possible vaccine antigen. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

Vaccination against δ-Retroviruses: The Bovine Leukemia Virus Paradigm

by Gerónimo Gutiérrez, Sabrina M. Rodríguez, Alix De Brogniez, Nicolas Gillet, Ramarao Golime, Arsène Burny, Juan-Pablo Jaworski, Irene Alvarez, Lucas Vagnoni, Karina Trono and Luc Willems

Viruses 2014, 6(6), 2416-2427; https://doi.org/10.3390/v6062416 - 20 Jun 2014

Cited by 62 | Viewed by 12420

Abstract

Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and [...] Read more.

Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related d-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and leukemia/lymphoma (adult T-cell leukemia). Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of d-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

Alphavirus-Based Vaccines

by Kenneth Lundstrom

Viruses 2014, 6(6), 2392-2415; https://doi.org/10.3390/v6062392 - 16 Jun 2014

Cited by 62 | Viewed by 11142

Abstract

Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis [...] Read more.

Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

Universal Influenza Vaccines, a Dream to Be Realized Soon

by Han Zhang, Li Wang, Richard W. Compans and Bao-Zhong Wang

Viruses 2014, 6(5), 1974-1991; https://doi.org/10.3390/v6051974 - 29 Apr 2014

Cited by 57 | Viewed by 9891

Abstract

Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for [...] Read more.

Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

Matrix and Backstage: Cellular Substrates for Viral Vaccines

by Ingo Jordan and Volker Sandig

Viruses 2014, 6(4), 1672-1700; https://doi.org/10.3390/v6041672 - 11 Apr 2014

Cited by 32 | Viewed by 11182

Abstract

Vaccines are complex products that are manufactured in highly dynamic processes. Cellular substrates are one critical component that can have an enormous impact on reactogenicity of the final preparation, level of attenuation of a live virus, yield of infectious units or antigens, and [...] Read more.

Vaccines are complex products that are manufactured in highly dynamic processes. Cellular substrates are one critical component that can have an enormous impact on reactogenicity of the final preparation, level of attenuation of a live virus, yield of infectious units or antigens, and cost per vaccine dose. Such parameters contribute to feasibility and affordability of vaccine programs both in industrialized countries and developing regions. This review summarizes the diversity of cellular substrates for propagation of viral vaccines from primary tissue explants and embryonated chicken eggs to designed continuous cell lines of human and avian origin. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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Open AccessReview

HSV-2 Vaccine: Current Status and Insight into Factors for Developing an Efficient Vaccine

by Xiao-Peng Zhu, Zaka S. Muhammad, Jian-Guang Wang, Wu Lin, Shi-Kun Guo and Wei Zhang

Viruses 2014, 6(2), 371-390; https://doi.org/10.3390/v6020371 - 24 Jan 2014

Cited by 39 | Viewed by 12465

Abstract

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate [...] Read more.

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate this process, the latest progress in development of these vaccines is reviewed in this paper. A summary of the most promising HSV-2 vaccines tested in animals in the last five years is presented, including the main factors, and new ideas for developing an effective vaccine from animal experiments and human clinical trials. Experimental results indicate that future HSV-2 vaccines may depend on a strategy that targets mucosal immunity. Furthermore, estradiol, which increases the effectiveness of vaccines, may be considered as an adjuvant. Therefore, this review is expected to provide possible strategies for development of future HSV-2 vaccines. Full article

(This article belongs to the Special Issue Virus-based Vaccines)

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