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Viruses
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Advances in Vaccines and Host-Targeted Therapeutics against Respiratory Viruses
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Advances in Vaccines and Host-Targeted Therapeutics against Respiratory Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 6560

Special Issue Editors

Dr. Husni Elbahesh

E-Mail Website
Guest Editor
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine (TiHo), Hanover, Germany
Interests: influenza; response modifiers; antiviral therapeutics; immune response; immunomodulators
Dr. Crystal W. Burke

E-Mail
Guest Editor
US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA
Interests: eastern equine encephalitis virus; alphavirus; togaviridae

Special Issue Information

Dear Colleagues,

Respiratory viruses as a group are responsible for infections that result in substantial morbidity, mortality and economic losses. Unlike previous SARS, MERS and H5N1 outbreaks, the devastating effects of the current SARS-Coronavirus 2 (SARS-CoV2) highlight our vulnerability to emerging zoonotic pathogens and their pandemic potential. In addition SARS-CoV2, influenza A and B viruses (IAV/IBV) remain at the forefront as significant threats to public health as they have caused numerous pandemics over the last century and perhaps more importantly, yearly epidemics that result in more than 500,000 yearly deaths world-wide. While less fatal to the general population, other respiratory viruses including human respiratory syncytial virus (hRSV), human parainfluenza virus (hPIV) and human metapneumovirus (hMPV) account for the majority of severe acute childhood respiratory disease including pneumonia.

While vaccines are the cornerstone of our defenses against SARS-CoV2 and IAV, vaccines are less effective in cases of novel emerging strains, antigenic drift/shift and resistance/escape mutations. Importantly, no licensed vaccines exist for important childhood respiratory viruses such as hRSV, hMPV and hPIV. These gaps require therapeutic antiviral interventions. While the majority of approved “antivirals” have been virus-directed, it is abundantly clear that this approach is vulnerable to resistance/escape mutations. Accordingly, there has been a concerted effort to identify host factors that can be directly targeted to limit viral replication, pathogenesis and/or transmission.

In this Special Issue, we hope to highlight some of these approaches using “non-traditional” vaccine designs, especially against hRSV, hMPV and hPIV as well as host-directed antiviral compounds that limit viral replication and/or limit tissue/host damage and promote regeneration and survival. Of special interest, are studies that “repurpose” clinically-approved compounds and those that potentially define novel host targets for therapeutic development and further our understanding of host-virus interactions with these important pathogens.

Dr. Husni Elbahesh
Dr. Crystal W. Burke
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vaccine development
  • therapeutics to viral infections
  • host-directed antiviral compounds
  • influenza viruses
  • SARS and SARS-CoV-2
  • MERS-CoV
  • human respiratory syncytial virus (hRSV)
  • human parainfluenza virus (hPIV)
  • human metapneumovirus (hMPV)
  • host–virus interactions

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Published Papers (2 papers)

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Research

19 pages, 14377 KiB  
Article
An Optimized FI-RSV Vaccine Effectively Protects Cotton Rats and BALB/c Mice without Causing Enhanced Respiratory Disease
by Min Lin, Wei Zhang, Yi-Fan Yin, Jun-Yu Si, Lu-Jing Zhang, Li Chen, Xue Lin, Ying-Bin Wang, Jun Zhang, Zi-Zheng Zheng and Ning-Shao Xia
Viruses 2022, 14(10), 2085; https://doi.org/10.3390/v14102085 - 20 Sep 2022
Cited by 4 | Viewed by 2989
Abstract
Background: Despite considerable efforts toward vaccine development in past decades, no effective vaccines against respiratory syncytial virus (RSV) are available. Recently, we showed that an optimized formalin concentration can preserve prefusion protein (pre-F) on RSV-infected cells and protect mice against RSV infection without [...] Read more.
Background: Despite considerable efforts toward vaccine development in past decades, no effective vaccines against respiratory syncytial virus (RSV) are available. Recently, we showed that an optimized formalin concentration can preserve prefusion protein (pre-F) on RSV-infected cells and protect mice against RSV infection without causing enhanced respiratory disease (ERD). Here, we sought to further stabilize pre-F on RSV virions by optimizing the production of FI-RSV. Methods: Freshly produced RSV virions were treated with formalin under different concentrations to obtained an opti-FI-RSV vaccine with high pre-F level. Immunogenicity and safety of opti-FI-RSV were evaluated in Balb/c mice and cotton rats. Results: Using 0.0156–0.1778% formalin, we successfully preserved pre-F on virions. This opti-FI-RSV exhibited improved immunogenicity and efficacy without causing ERD. Surprisingly, opti-FI-RSV, with a pre-F-dominant immunogen, still caused ERD after immunization with a suboptimal dose or when the neutralizing antibody titers declined. ERD was avoided by coadministering opti-FI-RSV with CpG + MPLA adjuvant, which subsequently induced a Th1-biasing immune response and, more importantly, significantly improved antibody avidity. Conclusions: Our study provides a new method to obtain a novel FI-RSV vaccine with a high pre-F level and may provide a reference for developing other inactivated vaccines. Our findings also emphasize that appropriate adjuvants are critical for nonreplicating vaccines. Full article
(This article belongs to the Special Issue Advances in Vaccines and Host-Targeted Therapeutics against Respiratory Viruses)
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19 pages, 2994 KiB  
Article
FDA-Approved Inhibitors of RTK/Raf Signaling Potently Impair Multiple Steps of In Vitro and Ex Vivo Influenza A Virus Infections
by Robert Meineke, Sonja Stelz, Maximilian Busch, Christopher Werlein, Mark Kühnel, Danny Jonigk, Guus F. Rimmelzwaan and Husni Elbahesh
Viruses 2022, 14(9), 2058; https://doi.org/10.3390/v14092058 - 16 Sep 2022
Cited by 9 | Viewed by 2812
Abstract
Influenza virus (IV) infections pose a burden on global public health with significant morbidity and mortality. The limited range of currently licensed IV antiviral drugs is susceptible to the rapid rise of resistant viruses. In contrast, FDA-approved kinase inhibitors can be repurposed as [...] Read more.
Influenza virus (IV) infections pose a burden on global public health with significant morbidity and mortality. The limited range of currently licensed IV antiviral drugs is susceptible to the rapid rise of resistant viruses. In contrast, FDA-approved kinase inhibitors can be repurposed as fast-tracked host-targeted antivirals with a higher barrier of resistance. Extending our recent studies, we screened 21 FDA-approved small-molecule kinase inhibitors (SMKIs) and identified seven candidates as potent inhibitors of pandemic and seasonal IV infections. These SMKIs were further validated in a biologically and clinically relevant ex vivo model of human precision-cut lung slices. We identified steps of the virus infection cycle affected by these inhibitors (entry, replication, egress) and found that most SMKIs affected both entry and egress. Based on defined and overlapping targets of these inhibitors, the candidate SMKIs target receptor tyrosine kinase (RTK)-mediated activation of Raf/MEK/ERK pathways to limit influenza A virus infection. Our data and the established safety profiles of these SMKIs support further clinical investigations and repurposing of these SMKIs as host-targeted influenza therapeutics. Full article
(This article belongs to the Special Issue Advances in Vaccines and Host-Targeted Therapeutics against Respiratory Viruses)
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