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13 pages, 2605 KiB

Open AccessArticle

Integrase Defective Lentiviral Vector Promoter Impacts Transgene Expression in Target Cells and Magnitude of Vector-Induced Immune Responses

by Sneha Mahesh, Jenny Li, Tatianna Travieso, Danai Psaradelli, Donatella Negri, Mary Klotman, Andrea Cara and Maria Blasi

Viruses 2023, 15(11), 2255; https://doi.org/10.3390/v15112255 - 14 Nov 2023

Viewed by 967

Abstract

Integrase defective lentiviral vectors (IDLVs) are a promising vaccine delivery platform given their ability to induce high magnitude and durable antigen-specific immune responses. IDLVs based on the simian immunodeficiency virus (SIV) are significantly more efficient at transducing human and simian dendritic cells (DCs) [...] Read more.

Integrase defective lentiviral vectors (IDLVs) are a promising vaccine delivery platform given their ability to induce high magnitude and durable antigen-specific immune responses. IDLVs based on the simian immunodeficiency virus (SIV) are significantly more efficient at transducing human and simian dendritic cells (DCs) compared to HIV-based vectors, resulting in a higher expansion of antigen-specific CD8+ T cells. Additionally, IDLV persistence and continuous antigen expression in muscle cells at the injection site contributes to the durability of the vaccine-induced immune responses. Here, to further optimize transgene expression levels in both DCs and muscle cells, we generated ten novel lentiviral vectors (LVs) expressing green fluorescent protein (GFP) under different hybrid promoters. Our data show that three of the tested hybrid promoters resulted in the highest transgene expression levels in mouse DCs, monkey DCs and monkey muscle cells. We then used the three LVs with the highest in vitro transgene expression levels to immunize BALB/c mice and observed high magnitude T cell responses at 3 months post-prime. Our study demonstrates that the choice of the vector promoter influences antigen expression levels in target cells and the ensuing magnitude of T cell responses in vivo. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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12 pages, 3151 KiB

Open AccessArticle

Two Point Mutations in the Glycoprotein of SFTSV Enhance the Propagation Recombinant Vesicular Stomatitis Virus Vectors at Assembly Step

by Qiang Hu, Yuhang Zhang, Jiafu Jiang and Aihua Zheng

Viruses 2023, 15(3), 800; https://doi.org/10.3390/v15030800 - 21 Mar 2023

Cited by 1 | Viewed by 1558

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen for which approved therapeutic drugs or vaccines are not available. We previously developed a recombinant vesicular stomatitis virus-based vaccine candidate (rVSV-SFTSV) by replacing the original glycoprotein with Gn/Gc from SFTSV, which [...] Read more.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen for which approved therapeutic drugs or vaccines are not available. We previously developed a recombinant vesicular stomatitis virus-based vaccine candidate (rVSV-SFTSV) by replacing the original glycoprotein with Gn/Gc from SFTSV, which conferred complete protection in a mouse model. Here, we found that two spontaneous mutations, M749T/C617R, emerged in the Gc glycoprotein during passaging that could significantly increase the titer of rVSV-SFTSV. M749T/C617R enhanced the genetic stability of rVSV-SFTSV, and no further mutations appeared after 10 passages. Using immunofluorescence analysis, we found that M749T/C617R could increase glycoprotein traffic to the plasma membrane, thus facilitating virus assembly. Remarkably, the broad-spectrum immunogenicity of rVSV-SFTSV was not affected by the M749T/C617R mutations. Overall, M749T/C617R could enhance the further development of rVSV-SFTSV into an effective vaccine in the future. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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15 pages, 2259 KiB

Open AccessArticle

An Adenovirus-Based Recombinant Herpes Simplex Virus 2 (HSV-2) Therapeutic Vaccine Is Highly Protective against Acute and Recurrent HSV-2 Disease in a Guinea Pig Model

by Mingming Wan, Xiao Yang, Jie Sun, Xue Ding, Zhijun Chen, Weiheng Su, Linjun Cai, Ali Hou, Bo Sun, Feng Gao, Chunlai Jiang and Yan Zhou

Viruses 2023, 15(1), 219; https://doi.org/10.3390/v15010219 - 13 Jan 2023

Cited by 2 | Viewed by 2660

Abstract

Genital herpes (GH) has become one of the most common sexually transmitted diseases worldwide, and it is spreading rapidly in developing countries. Approximately 90% of GH cases are caused by HSV-2. Therapeutic HSV-2 vaccines are intended for people already infected with HSV-2 with [...] Read more.

Genital herpes (GH) has become one of the most common sexually transmitted diseases worldwide, and it is spreading rapidly in developing countries. Approximately 90% of GH cases are caused by HSV-2. Therapeutic HSV-2 vaccines are intended for people already infected with HSV-2 with the goal of reducing clinical recurrences and recurrent virus shedding. In our previous work, we evaluated recombinant adenovirus-based vaccines, including rAd-gD2ΔUL25, rAd-ΔUL25, and rAd-gD2, for their potency as prophylactic vaccines. In this study, we evaluated these three vaccines as therapeutic vaccines against acute and recurrent diseases in intravaginal challenged guinea pigs. Compared with the control groups, the recombinant vaccine rAd-gD2ΔUL25 induced a higher titer of the binding antibody, and rAd-gD2 + rAd-ΔUL25 induced a higher titer of the neutralizing antibody. Both rAd-gD2ΔUL25 and rAd-gD2 + rAd-ΔUL25 vaccines significantly enhanced the survival rate by 50% compared to rAd-gD2 and reduced viral replication in the genital tract and recurrent genital skin disease. Our findings provide a new perspective for HSV-2 therapeutic vaccine research and provide a new technique to curtail the increasing spread of HSV-2. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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16 pages, 3908 KiB

Open AccessArticle

Baculovirus Display of Varicella–Zoster Virus Glycoprotein E Induces Robust Humoral and Cellular Immune Responses in Mice

by Wenhui Xue, Tingting Li, Sibo Zhang, Yingbin Wang, Minqing Hong, Lingyan Cui, Hong Wang, Yuyun Zhang, Tingting Chen, Rui Zhu, Zhenqin Chen, Lizhi Zhou, Rongwei Zhang, Tong Cheng, Qingbing Zheng, Jun Zhang, Ying Gu, Ningshao Xia and Shaowei Li

Viruses 2022, 14(8), 1785; https://doi.org/10.3390/v14081785 - 16 Aug 2022

Cited by 5 | Viewed by 2974

Abstract

Varicella–zoster virus (VZV) is the causative agent of varicella and herpes zoster (HZ) and can pose a significant challenge to human health globally. The initial VZV infection—more common in children—causes a self-limiting chicken pox. However, in later life, the latent VZV can become [...] Read more.

Varicella–zoster virus (VZV) is the causative agent of varicella and herpes zoster (HZ) and can pose a significant challenge to human health globally. The initial VZV infection—more common in children—causes a self-limiting chicken pox. However, in later life, the latent VZV can become reactivated in these patients, causing HZ and postherpetic neuralgia (PHN), a serious and painful complication. VZV glycoprotein E (gE) has been developed into a licensed subunit vaccine against HZ (Shingrix). However, its efficacy relies on the concomitant delivery of a robust adjuvant (AS01B). Here, we sought to create a new immunogen for vaccine design by displaying the VZV–gE on the baculovirus surface (Bac–gE). Correct localization and display of gE on the engineered baculovirus was verified by flow cytometry and immune electron microscopy. We show that Bac–gE provides excellent antigenicity against VZV and induces not only stronger gE-specific CD4⁺ and CD8⁺ T cell responses but also higher levels of VZV–specific neutralizing antibodies as compared with other vaccine strategies in mice. Collectively, we show that the baculovirus display of VZV–gE confers ideal humoral and cellular immune responses required for HZ vaccine development, paving the way for a baculovirus-based vaccine design. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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Review

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27 pages, 1355 KiB

Open AccessReview

Current Hepatitis C Vaccine Candidates Based on the Induction of Neutralizing Antibodies

by Elsa Gomez-Escobar, Philippe Roingeard and Elodie Beaumont

Viruses 2023, 15(5), 1151; https://doi.org/10.3390/v15051151 - 11 May 2023

Cited by 3 | Viewed by 2547

Abstract

The introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C treatment. Short courses of treatment with these drugs are highly beneficial to patients, eliminating hepatitis C virus (HCV) without adverse effects. However, this outstanding success is tempered by the continuing difficulty of eradicating [...] Read more.

The introduction of direct-acting antivirals (DAAs) has revolutionized hepatitis C treatment. Short courses of treatment with these drugs are highly beneficial to patients, eliminating hepatitis C virus (HCV) without adverse effects. However, this outstanding success is tempered by the continuing difficulty of eradicating the virus worldwide. Thus, access to an effective vaccine against HCV is strongly needed to reduce the burden of the disease and contribute to the elimination of viral hepatitis. The recent failure of a T-cell vaccine based on the use of viral vectors expressing the HCV non-structural protein sequences to prevent chronic hepatitis C in drug users has pointed out that the induction of neutralizing antibodies (NAbs) will be essential in future vaccine candidates. To induce NAbs, vaccines must contain the main target of this type of antibody, the HCV envelope glycoproteins (E1 and E2). In this review, we summarize the structural regions in E1 and E2 proteins that are targeted by NAbs and how these proteins are presented in the vaccine candidates currently under development. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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23 pages, 5064 KiB

Open AccessReview

Development of Next Generation Vaccines against SARS-CoV-2 and Variants of Concern

by Abdul Aziz Al-Fattah Yahaya, Kanwal Khalid, Hui Xuan Lim and Chit Laa Poh

Viruses 2023, 15(3), 624; https://doi.org/10.3390/v15030624 - 24 Feb 2023

Cited by 5 | Viewed by 2673

Abstract

SARS-CoV-2 has caused the COVID-19 pandemic, with over 673 million infections and 6.85 million deaths globally. Novel mRNA and viral-vectored vaccines were developed and licensed for global immunizations under emergency approval. They have demonstrated good safety and high protective efficacy against the SARS-CoV-2 [...] Read more.

SARS-CoV-2 has caused the COVID-19 pandemic, with over 673 million infections and 6.85 million deaths globally. Novel mRNA and viral-vectored vaccines were developed and licensed for global immunizations under emergency approval. They have demonstrated good safety and high protective efficacy against the SARS-CoV-2 Wuhan strain. However, the emergence of highly infectious and transmissible variants of concern (VOCs) such as Omicron was associated with considerable reductions in the protective efficacy of the current vaccines. The development of next-generation vaccines that could confer broad protection against both the SARS-CoV-2 Wuhan strain and VOCs is urgently needed. A bivalent mRNA vaccine encoding the Spike proteins of both the SARS-CoV-2 Wuhan strain and the Omicron variant has been constructed and approved by the US FDA. However, mRNA vaccines are associated with instability and require an extremely low temperature (−80 °C) for storage and transportation. They also require complex synthesis and multiple chromatographic purifications. Peptide-based next-generation vaccines could be developed by relying on in silico predictions to identify peptides specifying highly conserved B, CD4⁺ and CD8⁺ T cell epitopes to elicit broad and long-lasting immune protection. These epitopes were validated in animal models and in early phase clinical trials to demonstrate immunogenicity and safety. Next-generation peptide vaccine formulations could be developed to incorporate only naked peptides, but they are costly to synthesize and production would generate extensive chemical waste. Continual production of recombinant peptides specifying immunogenic B and T cell epitopes could be achieved in hosts such as E. coli or yeast. However, recombinant protein/peptide vaccines require purification before administration. The DNA vaccine might serve as the most effective next-generation vaccine for low-income countries, since it does not require an extremely low temperature for storage or need extensive chromatographic purification. The construction of recombinant plasmids carrying genes specifying highly conserved B and T cell epitopes meant that vaccine candidates representing highly conserved antigenic regions could be rapidly developed. Poor immunogenicity of DNA vaccines could be overcome by the incorporation of chemical or molecular adjuvants and the development of nanoparticles for effective delivery. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

32 pages, 3943 KiB

Open AccessReview

The Impact of Epitranscriptomics on Antiviral Innate Immunity

by Beril Mersinoglu, Sara Cristinelli and Angela Ciuffi

Viruses 2022, 14(8), 1666; https://doi.org/10.3390/v14081666 - 28 Jul 2022

Cited by 2 | Viewed by 2906

Abstract

Epitranscriptomics, i.e., chemical modifications of RNA molecules, has proven to be a new layer of modulation and regulation of protein expression, asking for the revisiting of some aspects of cellular biology. At the virological level, epitranscriptomics can thus directly impact the viral life [...] Read more.

Epitranscriptomics, i.e., chemical modifications of RNA molecules, has proven to be a new layer of modulation and regulation of protein expression, asking for the revisiting of some aspects of cellular biology. At the virological level, epitranscriptomics can thus directly impact the viral life cycle itself, acting on viral or cellular proteins promoting replication, or impacting the innate antiviral response of the host cell, the latter being the focus of the present review. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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22 pages, 1306 KiB

Open AccessReview

Think like a Virus: Toward Improving Nanovaccine Development against SARS-CoV-2

by Nura A. Mohamed, Haissam Abou-Saleh, Hana A. Mohamed, Mohammad A. Al-Ghouti, Sergio Crovella and Luisa Zupin

Viruses 2022, 14(7), 1553; https://doi.org/10.3390/v14071553 - 15 Jul 2022

Cited by 10 | Viewed by 2525

Abstract

There is no doubt that infectious diseases present global impact on the economy, society, health, mental state, and even political aspects, causing a long-lasting dent, and the situation will surely worsen if and when the viral spread becomes out of control, as seen [...] Read more.

There is no doubt that infectious diseases present global impact on the economy, society, health, mental state, and even political aspects, causing a long-lasting dent, and the situation will surely worsen if and when the viral spread becomes out of control, as seen during the still ongoing coronavirus disease 2019 (COVID-19) pandemic. Despite the considerable achievements made in viral prevention and treatment, there are still significant challenges that can be overcome through careful understanding of the viral mechanism of action to establish common ground for innovating new preventative and treatment strategies. Viruses can be regarded as devil nanomachines, and one innovative approach to face and stop the spread of viral infections is the development of nanoparticles that can act similar to them as drug/vaccine carriers. Moreover, we can use the properties that different viruses have in designing nanoparticles that reassemble the virus conformational structures but that do not present the detrimental threats to human health that native viruses possess. This review discusses the current preventative strategies (i.e., vaccination) used in facing viral infections and the associated limitations, highlighting the importance of innovating new approaches to face viral infectious diseases and discussing the current nanoapplications in vaccine development and the challenges that still face the nanovaccine field. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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14 pages, 1414 KiB

Open AccessReview

JAK-STAT Pathway: A Novel Target to Tackle Viral Infections

by Ifeanyi Jude Ezeonwumelu, Edurne Garcia-Vidal and Ester Ballana

Viruses 2021, 13(12), 2379; https://doi.org/10.3390/v13122379 - 27 Nov 2021

Cited by 36 | Viewed by 5761

Abstract

Modulation of the antiviral innate immune response has been proposed as a putative cellular target for the development of novel pan-viral therapeutic strategies. The Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway is especially relevant due to its essential role in the [...] Read more.

Modulation of the antiviral innate immune response has been proposed as a putative cellular target for the development of novel pan-viral therapeutic strategies. The Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway is especially relevant due to its essential role in the regulation of local and systemic inflammation in response to viral infections, being, therefore, a putative therapeutic target. Here, we review the extraordinary diversity of strategies that viruses have evolved to interfere with JAK-STAT signaling, stressing the relevance of this pathway as a putative antiviral target. Moreover, due to the recent remarkable progress on the development of novel JAK inhibitors (JAKi), the current knowledge on its efficacy against distinct viral infections is also discussed. JAKi have a proven efficacy against a broad spectrum of disorders and exhibit safety profiles comparable to biologics, therefore representing good candidates for drug repurposing strategies, including viral infections. Full article

(This article belongs to the Special Issue Advances in Antiviral Immunity and Virus Vaccines)

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