Poxvirus Mediated Immunity in Infection and Vaccination

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Infectious Diseases".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 11091

Special Issue Editor


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Guest Editor
Institute for Virology, Düsseldorf University Hospital, Heinrich-Heine-University, 40225 Dusseldorf, Germany
Interests: poxviruses; viral immunology; viral vector vaccines; immunization; T cell responses; antigen processing and presentation; innate immune sensing

Special Issue Information

Dear Colleagues,

Vaccination has never been more present and discussed in the public as now in the middle of the COVID-19 pandemic. The pandemic situation has dramatically enforced vaccine research and underlined the importance of a detailed understanding of viral immunopathology on one side and vaccine immunogenicity on the other side. Poxviruses have a long history for investigating both. Major breakthroughs have been reported on host sensing mechanisms and responses and poxvirus immune evasion strategies, with the implications these might have on the development of safer and more effective vaccines. The initial response after infection involves interferons and inflammation. Cell-mediated and humoral responses to viral antigens are important for recovery and subsequent long-lasting immunity. In addition, deep-sequencing technologies are unravelling the genomes of novel poxvirus species, shedding light on the evolutionary history of the family and its strategies for adaptation. It is significant that the strategies used for smallpox eradication are being assessed for the control and eradication of other diseases such as measles and that recombinant poxvirus vector vaccines may play an important role in the control of infections with future pathogens.

It is in this context of exciting discoveries and emerging concepts that Vaccines will launch a Special Issue on Poxvirus-mediated immunity in infection and vaccination that aims to collect new perspectives and insightful reviews on the biology of these unique viruses and their relation with the immune system and on new approaches for viral vector design, novel vaccine formulations with improved efficacy and optimized preventive and therapeutic immunization strategies.

Prof. Dr. Ingo Drexler
Guest Editor

Manuscript Submission Information

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Keywords

  • poxviruses
  • virus-host interactions
  • viral immune evasion
  • viral vectors and recombinant vaccines
  • adaptive immunity
  • innate immunity and inflammation
  • clinical and translational research

Published Papers (4 papers)

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Research

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12 pages, 16769 KiB  
Article
Orally Administrated Recombinant Vaccinia Virus Displaying ROP4 Induces Protection against Toxoplasma gondii Challenge Infection
by Keon-Woong Yoon, Ki-Back Chu, Hae-Ji Kang, Min-Ju Kim, Gi-Deok Eom and Fu-Shi Quan
Vaccines 2022, 10(2), 152; https://doi.org/10.3390/vaccines10020152 - 20 Jan 2022
Cited by 2 | Viewed by 1807
Abstract
Recombinant vaccinia viruses (rVVs) are attenuated viruses and are widely utilized as vectored vaccine platforms against numerous diseases. However, the protective efficacy of these rVV vaccines against Toxoplasma gondii and the resulting mucosal immunity has not been thoroughly assessed. Here, rVVs expressing the [...] Read more.
Recombinant vaccinia viruses (rVVs) are attenuated viruses and are widely utilized as vectored vaccine platforms against numerous diseases. However, the protective efficacy of these rVV vaccines against Toxoplasma gondii and the resulting mucosal immunity has not been thoroughly assessed. Here, rVVs expressing the rhoptry protein 4 (ROP4) of T. gondii were generated. To evaluate the protection induced by the vaccines, mice were orally immunized with the ROP4-rVVs and subsequently challenge-infected with a lethal dose of T. gondii ME49 strain. Immunization with the rVVs induced higher levels of parasite-specific IgG and IgA antibody responses in sera compared to unimmunized control (NC). Upon challenge infection, significantly higher levels of IgG or IgA antibody responses in the brain, intestines, and vaginal samples were found in the immunized mice compared to NC. The ROP4-rVV vaccination elicited potent IgG and IgA secreting cell (ASC) responses, while substantially enhancing germinal center B cell, as well as CD4+ and CD8+ T cell responses from lymphoid organs. The production of pro-inflammatory cytokines IFN-γ and IL-6 in the brains was markedly diminished following immunization. The immunized mice also experienced reduced bodyweight loss and possessed fewer brain cysts than the control group. These results suggest that oral delivery of ROP4 displaying rVVs induced mucosal and systemic immunities that contributed to protection against lethal T. gondii challenge infection. Full article
(This article belongs to the Special Issue Poxvirus Mediated Immunity in Infection and Vaccination)
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12 pages, 2265 KiB  
Article
Impact of Molecular Modifications on the Immunogenicity and Efficacy of Recombinant Raccoon Poxvirus-Vectored Rabies Vaccine Candidates in Mice
by Carly M. Malavé, Jaime Lopera-Madrid, Lex G. Medina-Magües, Tonie E. Rocke and Jorge E. Osorio
Vaccines 2021, 9(12), 1436; https://doi.org/10.3390/vaccines9121436 - 4 Dec 2021
Cited by 1 | Viewed by 2704
Abstract
Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order Chiroptera) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is [...] Read more.
Rabies is an ancient disease that is responsible for approximately 59,000 human deaths annually. Bats (Order Chiroptera) are thought to be the original hosts of rabies virus (RABV) and currently account for most rabies cases in wildlife in the Americas. Vaccination is being used to manage rabies in other wildlife reservoirs like fox and raccoon, but no rabies vaccine is available for bats. We previously developed a recombinant raccoonpox virus (RCN) vaccine candidate expressing a mosaic glycoprotein (MoG) gene that protected mice and big brown bats when challenged with RABV. In this study, we developed two new recombinant RCN candidates expressing MoG (RCN-tPA-MoG and RCN-SS-TD-MoG) with the aim of improving RCN-MoG. We assessed and compared in vitro expression, in vivo immunogenicity, and protective efficacy in vaccinated mice challenged intracerebrally with RABV. All three candidates induced significant humoral immune responses, and inoculation with RCN-tPA-MoG or RCN-MoG significantly increased survival after RABV challenge. These results demonstrate the importance of considering molecular elements in the design of vaccines, and that vaccination with either RCN-tPA-MoG or RCN-MoG confers adequate protection from rabies infection, and either may be a sufficient vaccine candidate for bats in future work. Full article
(This article belongs to the Special Issue Poxvirus Mediated Immunity in Infection and Vaccination)
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27 pages, 6636 KiB  
Article
Characterization of an In Vivo Neutralizing Anti-Vaccinia Virus D8 Single-Chain Fragment Variable (scFv) from a Human Anti-Vaccinia Virus-Specific Recombinant Library
by Ulrike S. Diesterbeck, Henrike P. Ahsendorf, André Frenzel, Ahmad Reza Sharifi, Thomas Schirrmann and Claus-Peter Czerny
Vaccines 2021, 9(11), 1308; https://doi.org/10.3390/vaccines9111308 - 10 Nov 2021
Cited by 3 | Viewed by 2584
Abstract
A panel of potent neutralizing antibodies are protective against orthopoxvirus (OPXV) infections. For the development of OPXV-specific recombinant human single-chain antibodies (scFvs), the IgG repertoire of four vaccinated donors was amplified from peripheral B-lymphocytes. The resulting library consisted of ≥4 × 108 [...] Read more.
A panel of potent neutralizing antibodies are protective against orthopoxvirus (OPXV) infections. For the development of OPXV-specific recombinant human single-chain antibodies (scFvs), the IgG repertoire of four vaccinated donors was amplified from peripheral B-lymphocytes. The resulting library consisted of ≥4 × 108 independent colonies. The immuno-screening against vaccinia virus (VACV) Elstree revealed a predominant selection of scFv clones specifically binding to the D8 protein. The scFv-1.2.2.H9 was engineered into larger human scFv-Fc-1.2.2.H9 and IgG1-1.2.2.H9 formats to improve the binding affinity and to add effector functions within the human immune response. Similar binding kinetics were calculated for scFv-1.2.2.H9 and scFv-Fc-1.2.2.H9 (1.61 nM and 7.685 nM, respectively), whereas, for IgG1-1.2.2.H9, the Michaelis-Menten kinetics revealed an increased affinity of 43.8 pM. None of the purified recombinant 1.2.2.H9 formats were able to neutralize VACV Elstree in vitro. After addition of 1% human complement, the neutralization of ≥50% of VACV Elstree was achieved with 0.0776 µM scFv-Fc-1.2.2.H9 and 0.01324 µM IgG1-1.2.2.H9, respectively. In an in vivo passive immunization NMRI mouse model, 100 µg purified scFv-1.2.2.H9 and the IgG1-1.2.2.H9 partially protected against the challenge with 4 LD50 VACV Munich 1, as 3/6 mice survived. In contrast, in the scFv-Fc-1.2.2.H9 group, only one mouse survived the challenge. Full article
(This article belongs to the Special Issue Poxvirus Mediated Immunity in Infection and Vaccination)
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Review

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16 pages, 639 KiB  
Review
Development of Modified Vaccinia Virus Ankara-Based Vaccines: Advantages and Applications
by Olga Vladimirovna Orlova, Dina Viktorovna Glazkova, Elena Vladimirovna Bogoslovskaya, German Alexandrovich Shipulin and Sergey Mikhailovich Yudin
Vaccines 2022, 10(9), 1516; https://doi.org/10.3390/vaccines10091516 - 13 Sep 2022
Cited by 9 | Viewed by 3178
Abstract
Modified vaccinia virus Ankara (MVA) is a promising viral vector for vaccine development. MVA is well studied and has been widely used for vaccination against smallpox in Germany. This review describes the history of the origin of the virus and its properties as [...] Read more.
Modified vaccinia virus Ankara (MVA) is a promising viral vector for vaccine development. MVA is well studied and has been widely used for vaccination against smallpox in Germany. This review describes the history of the origin of the virus and its properties as a vaccine, including a high safety profile. In recent years, MVA has found its place as a vector for the creation of vaccines against various diseases. To date, a large number of vaccine candidates based on the MVA vector have already been developed, many of which have been tested in preclinical and clinical studies. We discuss data on the immunogenicity and efficacy of some of these vaccines. Full article
(This article belongs to the Special Issue Poxvirus Mediated Immunity in Infection and Vaccination)
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