Special Issue "Herpesvirus Vaccines"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Clinical Immunology".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Dr. Stefano Petrini
E-Mail Website
Guest Editor
1. School of Biosciences and Veterinary Medicine, University of Camerino, Via Circonvallazione 93/95, 62024 Matelica (MC), Italy;
2. Head of the National Reference Laboratory for Infectious Bovine Rhinotracheitis (IBR) at the Virology Dept. of Istituto Zooprofilattico Sperimentale Umbria-Marche, Via Gaetano Salvemini 1, 06126 Perugia (PG), Italy
Interests: Herpesviruses; Pestiviruses; African Swine Fever Virus; Circovirus; Swine Influenza virus; Porcine Respiratory and Reproductive Syndrome Virus; Cell Biology; DNA immunization; Chimeric Vaccines; Experimental infection in vivo and in vitro under BSL3 facilities
Dr. Peter Maple
E-Mail Website
Guest Editor
Research Group in Clinical Neurology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
Interests: a longstanding interest in the clinical aspects of human herpesviruses: diagnosis; epidemiology; immunology; pathology; vaccinology. Currently: investigating the interactions of herpesviruses infections with autoimmune/inflammatory mediated neurological diseases e.g., multiple sclerosis and working on aspects of SARS-CoV-2 infection

Special Issue Information

Dear Colleagues,

Herpesviruses are distributed widely throughout the animal kingdom and are responsible for several human and veterinary diseases.  A key characteristic of herpesvirus infections is the establishment of latency in which the virus persists lifelong in the host following primary infection.  Herpesviruses achieve a latent state with the host through the adoption of a range of strategies including existing in a virtually non-replicating state and producing certain proteins downregulating the hosts’ specific immune responses.  Periodically, herpesviruses may reactivate from the latent state to a replicating, lytic state involving the production of new proteins which may manifest new disease in the host and instigate an active immune response.  In humans, eight herpesviruses have been described including Herpes Simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), and Epstein Barr virus (EBV) which are responsible for several diseases following primary infection and reactivation. In many instances, primary infections are mild and self-limiting (eg. chickenpox); however, if the host’s immune responses are deficient or suppressed serious and potentially life-threatening infections may result.  In veterinary medicine, different herpesvirus infections (eg. Bovine herpesvirus; Bubaline herpesvirus; Equine herpesvirus; Ovine herpesvirus; Caprine herpesvirus) are responsible of serious economic losses for the animal farms. Although effective vaccines are available against some human herpesviruses (eg. VZV) and different animal herpesviruses (Bovine alphaherpesvirus 1, BoHV-1; Equine alphaherpesvirus 1/4, EHV1/4; Suid alphaherpesvirus 1, SuHV-1), there is an ongoing need to develop vaccines for other human (eg. CMV, EBV, HSV) and animal herpesviruses (eg. Bovine alphaherpesvirus 2, BoHV2; Bovine alphaherpesvirus 5, BoHV-5; Bubaline alphaherpesvirus 1, BuHV-1; Caprine alphaherpesvirus 1; CpHV-1; Ovine gammaherpesvirus 2, OvHV-2). The protective measures aimed to control different animal herpesviruses infection include immunization with live attenuated or inactivated vaccines. An additional area of development specifically relevant to herpesviruses of veterinary importance is the use of marker vaccines. These products by appropriate laboratory tests, offer the possibility of differentiating between natural infected and vaccinated animals. Finally, there is interest in the use of herpesviruses as vectors for transmitting heterologous immunogens.  The development of effective herpesvirus vaccines has proved challenging and various technological approaches have been undertaken to develop and evaluate new herpesvirus vaccines with differing levels of success. 

Dr. Stefano Petrini
Dr. Peter Maple
Guest Editors

Manuscript Submission Information

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Keywords

  • Herpersvirus
  • vaccines

Published Papers (4 papers)

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Research

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Article
Immunization with Human Cytomegalovirus Core Fusion Machinery and Accessory Envelope Proteins Elicit Strong Synergistic Neutralizing Activities
Vaccines 2020, 8(2), 179; https://doi.org/10.3390/vaccines8020179 - 13 Apr 2020
Cited by 2 | Viewed by 952
Abstract
Human cytomegalovirus (HCMV) core fusion machinery proteins gB and gH/gL, and accessory proteins UL128/UL130/UL131A, are the key envelope proteins that mediate HCMV entry into and infection of host cells. To determine whether these HCMV envelope proteins could elicit neutralizing activities synergistically, we immunized [...] Read more.
Human cytomegalovirus (HCMV) core fusion machinery proteins gB and gH/gL, and accessory proteins UL128/UL130/UL131A, are the key envelope proteins that mediate HCMV entry into and infection of host cells. To determine whether these HCMV envelope proteins could elicit neutralizing activities synergistically, we immunized rabbits with individual or various combinations of these proteins adsorbed to aluminum hydroxide mixed with CpG-ODN. We then analyzed serum neutralizing activities with multiple HCMV laboratory strains and clinical isolates. HCMV trimeric gB and gH/gL elicited high and moderate titers of HCMV neutralizing activity, respectively. HCMV gB in combination with gH/gL elicited up to 17-fold higher HCMV neutralizing activities compared to the sum of neutralizing activity elicited by the individual proteins analyzed with both fibroblasts and epithelial cells. HCMV gB+gH/gL+UL128/UL130/UL131A in combination increased the neutralizing activity up to 32-fold compared to the sum of neutralizing activities elicited by the individual proteins analyzed with epithelial cells. Adding UL128/UL130/UL131A to gB and gH/gL combination did not increase further the HCMV neutralizing activity analyzed with fibroblasts. These data suggest that the combination of HCMV core fusion machinery envelope proteins gB+gH/gL or the combination of gB and pentameric complex could be ideal vaccine candidates that would induce optimal immune responses against HCMV infection. Full article
(This article belongs to the Special Issue Herpesvirus Vaccines)
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Article
Evaluation of Passive Immunity Induced by Immunisation Using Two Inactivated gE-deleted Marker Vaccines against Infectious Bovine Rhinotracheitis (IBR) in Calves
Vaccines 2020, 8(1), 14; https://doi.org/10.3390/vaccines8010014 - 04 Jan 2020
Cited by 3 | Viewed by 1162
Abstract
Different types of vaccines against Infectious Bovine Rhinotracheitis (IBR) are commercially available. Among these, inactivated glycoprotein E (gE)-deleted marker vaccines are commonly used, but their ability to induce passive immunity is poorly known. Here, we evaluated the passive immunity transferred from dams immunised [...] Read more.
Different types of vaccines against Infectious Bovine Rhinotracheitis (IBR) are commercially available. Among these, inactivated glycoprotein E (gE)-deleted marker vaccines are commonly used, but their ability to induce passive immunity is poorly known. Here, we evaluated the passive immunity transferred from dams immunised with commercial inactivated gE-deleted marker vaccines to calves. We vaccinated 12 pregnant cattle devoid of neutralising antibodies against Bovine alphaherpesvirus 1 (BoHV-1) and divided them into two groups with 6 animals each. Both groups were injected with a different inactivated gE-deleted marker vaccine administrated via intranasal or intramuscular routes. An additional 6 pregnant cattle served as the unvaccinated control group. After calving, the number of animals in each group was increased by the newborn calves. In the dams, the humoral immune response was evaluated before calving and, subsequently, at different times until post-calving day 180 (PCD180). In addition, the antibodies in colostrum, milk, and in serum samples from newborn calves were evaluated at different times until PCD180. The results indicated that inactivated glycoprotein E (gE)-deleted marker vaccines are safe and produce a good humoral immune response in pregnant cattle until calving and PCD180. Moreover, results showed that, in calf serum, passive immunity persists until PCD180. Full article
(This article belongs to the Special Issue Herpesvirus Vaccines)
Article
Simultaneous Deletion of Virulence Factors and Insertion of Antigens into the Infectious Laryngotracheitis Virus Using NHEJ-CRISPR/Cas9 and Cre–Lox System for Construction of a Stable Vaccine Vector
Vaccines 2019, 7(4), 207; https://doi.org/10.3390/vaccines7040207 - 05 Dec 2019
Cited by 6 | Viewed by 1479
Abstract
Infectious laryngotracheitis virus (ILTV) is a promising vaccine vector due to its heterologous gene accommodation capabilities, low pathogenicity, and potential to induce cellular and humoral arms of immunity. Owing to these characteristics, different gene-deletion versions of ILTVs have been successfully deployed as a [...] Read more.
Infectious laryngotracheitis virus (ILTV) is a promising vaccine vector due to its heterologous gene accommodation capabilities, low pathogenicity, and potential to induce cellular and humoral arms of immunity. Owing to these characteristics, different gene-deletion versions of ILTVs have been successfully deployed as a vector platform for the development of recombinant vaccines against multiple avian viruses using conventional recombination methods, which are tedious, time-demanding, and error-prone. Here, we applied a versatile, and customisable clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 accompanied with Cre–Lox system to simultaneously delete virulence factors and to insert foreign genes in the ILTV genome. Using this pipeline, we successfully deleted thymidine kinase (TK) and unique short 4 (US4) genes and inserted fusion (F) gene of the Newcastle disease virus without adversely affecting ILTV replication and expression of the F protein. Taken together, the proposed approach offers novel tools to attenuate (by deletion of virulence factor) and to generate multivalent (by insertion of heterologous genes) vaccine vectors to protect chickens against pathogens of poultry and public health importance. Full article
(This article belongs to the Special Issue Herpesvirus Vaccines)
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Review

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Review
Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development
Vaccines 2020, 8(1), 35; https://doi.org/10.3390/vaccines8010035 - 20 Jan 2020
Cited by 4 | Viewed by 1449
Abstract
Herpesviruses have been isolated from a wide range of hosts including humans—for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from [...] Read more.
Herpesviruses have been isolated from a wide range of hosts including humans—for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital cytomegalovirus (CMV) infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of Epstein–Barr virus (EBV) infection with multiple sclerosis (MS) and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries, where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV-associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS and, in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine and, in order to progress the development of EBV vaccines for preventing MS, a greater understanding of the association of EBV with MS is required. Full article
(This article belongs to the Special Issue Herpesvirus Vaccines)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Evaluation of Passive Immunity Induced by Immunisation Using Two Inactivated gE-deleted Marker Vaccines against Infectious Bovine Rhinotracheitis (IBR) in Calves
Authors: Stefano Petrini; Cecilia Righi; Carmen Iscaro; Giulio Viola; Paola Gobbi; Eleonora Scoccia; Elisabetta Rossi; Claudia Pellegrini; Gian Mario De Mia
Affiliation: 1. National Reference Laboratory for Infectious Bovine Rhinotracheitis (IBR), Istituto Zooprofilattico Sperimentale Umbria-Marche “Togo Rosati”, 06126 Perugia, Italy; [email protected] (C.R.); [email protected] (C.I.); [email protected] (P.G.); [email protected] (E.S.); [email protected] (E.R.); [email protected] (C.P.); [email protected] (G.D.) 2. Veterinary Practitioner, 62026 San Ginesio, Italy; [email protected]
Abstract: To date, different types of vaccines against infectious bovine rhinotracheitis (IBR) are commercially available. Among these, inactivated gE-deleted marker vaccines are offered, but their ability to induce passive immunity is poor known. To evaluate passive immunity transferred from dams to calves via maternal immunisation with commercial inactivated gE-deleted marker vaccines, we performed several experiments. For this, we vaccinated 12 pregnant cattle devoid of neutralizing antibodies to Bovine alphaherpesvirus 1 (BoHV-1) and divided them into two groups with six animals each. Each group was injected with a different inactivated gE-deleted marker vaccine administrated via intranasal or intramuscular routes. An additional group served as the unvaccinated control. After calving, the pregnant cattle were increased by the respective newborn calves. In the dams, the humoral immune response was evaluated before calving and subsequently at different times until post-calving day (PCD) 180. In addition, passive immunity was evaluated in colostrum, milk, and in serum samples of the newborn calves at different times until PCD180. The results indicated that the vaccines used are safe and produce a good humoral immune response in pregnant cattle until calving and PCD180. Moreover, in calve serum, passive immunity persisted until PCD180.

Title: Simultaneous Deletion of Virulence Factors and Insertion of Antigens into the Infectious Laryngotracheitis Virus using NHEJ-CRISPR/Cas9 and Cre-Lox System for Construction of an Improved Vaccine Vector
Authors: Mustafa Ozan Atasoy; Mohammed A. Rohaim; Muhammad Munir
Affiliation: Lancaster University
Abstract: Infectious laryngotracheitis virus (ILTV) is a promising vaccine vector due to its heterologous genes accommodation capabilities, low pathogenicity, and potential to induce cellular and humoral immunity. Owing to these characteristics, different gene-deletion versions of ILTV have been successfully deployed as a vector platform for the development of recombinant vaccines against multiple avian viruses using conventional recombination methods, which are tedious, time demanding and error-prone. Here we applied a versatile, and customizable clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 accompanied with Cre-Lox system to simultaneously delete virulence factors and to insert foreign genes in the ILTV genome. Using this pipeline, we successfully deleted thymidine kinase (TK) and unique short 4 (US4) genes and inserted fusion (F) gene of the Newcastle disease virus without adversely affecting ILTV replication and expression of the F protein. Taken together, the proposed approach offers novel tools to attenuate (by deletion of virulence factor) and to generate multivalent (by insertion of heterologous genes) vaccines vector for protection of chicken against pathogens of poultry and public health importance.

Title: Cytomegalovirus and Epstein-Barr virus associations with neurological diseases and the need for vaccine development
Authors: Peter Maple
Affiliation: Clinical Neurology Research Group, Division of Clinical Neuroscience, University of Nottingham School of Medicine; Queen’s Medical Centre, Nottingham NG7 2UH
Abstract: Herpesviruses have been isolated from a wide range of hosts including humans for which 9 species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency allowing them to survive in the host for life effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital CMV infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of EBV infection with multiple sclerosis (MS), and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent both primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS, and in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine, and in order to progress the development of EBV vaccines for preventing MS a greater understanding of the association of EBV with MS is required.

Title: Immunization with Human Cytomegalovirus Core Fusion Machinery and Accessory Envelope Proteins Elicit Strong Synergistic Neutralizing Activities
Authors: Xinle Cui; Zhouhong Cao; Shuishu Wang; Stuart P. Adler; Michael A. McVoy; Clifford M. Snapper
Affiliation: Uniformed Services University of the Health Sciences
Abstract: Human cytomegalovirus (HCMV) core fusion machinery proteins gB, gH/gL and accessory proteins UL128/UL130/UL131A are the key envelope proteins that mediate HCMV entry into and infection of host cells. To determine whether these HCMV envelope proteins could elicit neutralizing activities synergistically, we immunized rabbits with individual or various combination of these proteins adsorbed to aluminum hydroxide mixed with CpG-ODN, and analyzed serum neutralizing activities with multiple HCMV laboratory strains and clinical isolates. HCMV trimeric gB and gH/gL elicited high and moderate titers of HCMV neutralizing activity respectively. HCMV gB in combination with gH/gL elicited up to 17-fold higher HCMV neutralizing activity compared to the sum of neutralizing activity elicited by the individual proteins analyzed with both fibroblasts and epithelial cells. HCMV gB+gH/gL+UL128/UL130/UL131A in combination increased the neutralizing activity up to 32-fold compared to the sum of neutralizing activity elicited by the individual proteins analyzed with epithelial cells. Adding UL128/UL130/UL131A to gB and gH/gL combination did not increase further the HCMV neutralizing activity analyzed with fibroblasts. These data suggest that the combination of HCMV core fusion machinery envelope proteins gB+gH/gL or the combination of gB and pentameric complex could be ideal vaccine candidates that would induce optimal immune response against HCMV infection.

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