A Modern Take on Replicating Viral Vaccines

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Attenuated/Inactivated/Live and Vectored Vaccines".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 10058

Special Issue Editors

Viral Special Pathogens Branch, Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USA
Interests: virology; Ebola; filovirus; Lassa; arenavirus; Rift Valley fever virus; vaccine development; diagnostics; assay development
National Infectious Diseases Laboratories, Boston University, Boston, MA, USA
Interests: medical countermeasure development for high-consequence viruses; animal model development; filovirus; arenavirus; henipavirus

Special Issue Information

Dear Colleagues, 

Arguably the greatest accomplishments in curtailing viral diseases have been made possible by live-attenuated vaccines. Modern molecular techniques and research into virology, immunology, and pathogenesis enable rational design of attenuation and the use of viral vectors. Yet, replicating vaccines seem to be going out of fashion. Is there still a place for live vaccines, or have other approaches, like mRNA, made them obsolete?

This Special Issue welcomes articles that probe various topics around live-attenuated virus and vectored virus vaccine candidates against important human and animal viral diseases. We welcome rational attenuation strategies, characterization of natural strain variation, efficacy and safety results in animal models and the clinic, studies of genetic stability, immunological correlates of protection, and comparative pathology. In addition, we are also interested in reports on reversion, shedding, or other topics with safety implications.

Let us make this Special Issue a thought-provoking forum on the possibilities and special considerations of this approach! 

We look forward to reading about your research. 

Kind regards
Markus and Anthony

Dr. Markus Kainulainen
Dr. Anthony Griffiths
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. Vaccines 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 2700 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

  • viral vaccine
  • live-attenuated vaccine
  • replication-competent vaccine
  • rational attenuation
  • codon deoptimization
  • single-cycle replication
  • vaccine safety
  • genetic stability
  • correlates of protection
  • comparative pathology
  • vaccine reversion
  • vaccine shedding

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

18 pages, 3355 KiB  
Article
Development of an Integrated Continuous Manufacturing Process for the rVSV-Vectored SARS-CoV-2 Candidate Vaccine
by Zeyu Yang, Barbara Cristina Martins Fernandes Paes, Julia Puppin Chaves Fulber, Michelle Yen Tran, Omar Farnós and Amine A. Kamen
Vaccines 2023, 11(4), 841; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines11040841 - 14 Apr 2023
Cited by 2 | Viewed by 1872
Abstract
The administration of viral vectored vaccines remains one of the most effective ways to respond to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. However, pre-existing immunity to the viral vector hinders its potency, resulting in a limited choice of viral vectors. Moreover, [...] Read more.
The administration of viral vectored vaccines remains one of the most effective ways to respond to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. However, pre-existing immunity to the viral vector hinders its potency, resulting in a limited choice of viral vectors. Moreover, the basic batch mode of manufacturing vectored vaccines does not allow one to cost-effectively meet the global demand for billions of doses per year. To date, the exposure of humans to VSV infection has been limited. Therefore, a recombinant vesicular stomatitis virus (rVSV), which expresses the spike protein of SARS-CoV-2, was selected as the vector. To determine the operating upstream process conditions for the most effective production of an rVSV-SARS-CoV-2 candidate vaccine, a set of critical process parameters was evaluated in an Ambr 250 modular system, whereas in the downstream process, a streamlined process that included DNase treatment, clarification, and a membrane-based anion exchange chromatography was developed. The design of the experiment was performed with the aim to obtain the optimal conditions for the chromatography step. Additionally, a continuous mode manufacturing process integrating upstream and downstream steps was evaluated. rVSV-SARS-CoV-2 was continuously harvested from the perfusion bioreactor and purified by membrane chromatography in three columns that were operated sequentially under a counter-current mode. Compared with the batch mode, the continuous mode of operation had a 2.55-fold increase in space–time yield and a reduction in the processing time by half. The integrated continuous manufacturing process provides a reference for the efficient production of other viral vectored vaccines. Full article
(This article belongs to the Special Issue A Modern Take on Replicating Viral Vaccines)
Show Figures

Figure 1

23 pages, 2505 KiB  
Article
Protective CD8+ T Cell Response Induced by Modified Vaccinia Virus Ankara Delivering Ebola Virus Nucleoprotein
by Alexandra Kupke, Asisa Volz, Erik Dietzel, Astrid Freudenstein, Jörg Schmidt, Hosam Shams-Eldin, Sylvia Jany, Lucie Sauerhering, Verena Krähling, Michelle Gellhorn Serra, Christiane Herden, Markus Eickmann, Stephan Becker and Gerd Sutter
Vaccines 2022, 10(4), 533; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10040533 - 29 Mar 2022
Cited by 4 | Viewed by 2335
Abstract
The urgent need for vaccines against Ebola virus (EBOV) was underscored by the large outbreak in West Africa (2014–2016). Since then, several promising vaccine candidates have been tested in pre-clinical and clinical studies. As a result, two vaccines were approved for human use [...] Read more.
The urgent need for vaccines against Ebola virus (EBOV) was underscored by the large outbreak in West Africa (2014–2016). Since then, several promising vaccine candidates have been tested in pre-clinical and clinical studies. As a result, two vaccines were approved for human use in 2019/2020, of which one includes a heterologous adenovirus/Modified Vaccinia virus Ankara (MVA) prime-boost regimen. Here, we tested new vaccine candidates based on the recombinant MVA vector, encoding the EBOV nucleoprotein (MVA-EBOV-NP) or glycoprotein (MVA-EBOV-GP) for their efficacy after homologous prime-boost immunization in mice. Our aim was to investigate the role of each antigen in terms of efficacy and correlates of protection. Sera of mice vaccinated with MVA-EBOV-GP were virus-neutralizing and MVA-EBOV-NP immunization readily elicited interferon-γ-producing NP-specific CD8+ T cells. While mock-vaccinated mice succumbed to EBOV infection, all vaccinated mice survived and showed drastically decreased viral loads in sera and organs. In addition, MVA-EBOV-NP vaccinated mice became susceptible to lethal EBOV infection after depletion of CD8+ T cells prior to challenge. This study highlights the potential of MVA-based vaccines to elicit humoral immune responses as well as a strong and protective CD8+ T cell response and contributes to understanding the possible underlying mechanisms. Full article
(This article belongs to the Special Issue A Modern Take on Replicating Viral Vaccines)
Show Figures

Figure 1

Review

Jump to: Research

15 pages, 1413 KiB  
Review
Perspectives of Next-Generation Live-Attenuated Rift Valley Fever Vaccines for Animal and Human Use
by Paul J. Wichgers Schreur, Brian H. Bird, Tetsuro Ikegami, Erick Bermúdez-Méndez and Jeroen Kortekaas
Vaccines 2023, 11(3), 707; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines11030707 - 21 Mar 2023
Cited by 4 | Viewed by 1707
Abstract
Live-attenuated Rift Valley fever (RVF) vaccines transiently replicate in the vaccinated host, thereby effectively initiating an innate and adaptive immune response. Rift Valley fever virus (RVFV)-specific neutralizing antibodies are considered the main correlate of protection. Vaccination with classical live-attenuated RVF vaccines during gestation [...] Read more.
Live-attenuated Rift Valley fever (RVF) vaccines transiently replicate in the vaccinated host, thereby effectively initiating an innate and adaptive immune response. Rift Valley fever virus (RVFV)-specific neutralizing antibodies are considered the main correlate of protection. Vaccination with classical live-attenuated RVF vaccines during gestation in livestock has been associated with fetal malformations, stillbirths, and fetal demise. Facilitated by an increased understanding of the RVFV infection and replication cycle and availability of reverse genetics systems, novel rationally-designed live-attenuated candidate RVF vaccines with improved safety profiles have been developed. Several of these experimental vaccines are currently advancing beyond the proof-of-concept phase and are being evaluated for application in both animals and humans. We here provide perspectives on some of these next-generation live-attenuated RVF vaccines and highlight the opportunities and challenges of these approaches to improve global health. Full article
(This article belongs to the Special Issue A Modern Take on Replicating Viral Vaccines)
Show Figures

Figure 1

14 pages, 331 KiB  
Review
Utilization of Viral Vector Vaccines in Preparing for Future Pandemics
by Kimberly A. Hofmeyer, Katherine M. Bianchi and Daniel N. Wolfe
Vaccines 2022, 10(3), 436; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10030436 - 12 Mar 2022
Cited by 5 | Viewed by 3525
Abstract
As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks [...] Read more.
As the global response to COVID-19 continues, government stakeholders and private partners must keep an eye on the future for the next emerging viral threat with pandemic potential. Many of the virus families considered to be among these threats currently cause sporadic outbreaks of unpredictable size and timing. This represents a major challenge in terms of both obtaining sufficient funding to develop vaccines, and the ability to evaluate clinical efficacy in the field. However, this also presents an opportunity in which vaccines, along with robust diagnostics and contact tracing, can be utilized to respond to outbreaks as they occur, and limit the potential for further spread of the disease in question. While mRNA-based vaccines have proven, during the COVID-19 response, to be an effective and safe solution in terms of providing a rapid response to vaccine development, virus vector-based vaccines represent a class of vaccines that can offer key advantages in certain performance characteristics with regard to viruses of pandemic potential. Here, we will discuss some of the key pros and cons of viral vector vaccines in the context of preparing for future pandemics. Full article
(This article belongs to the Special Issue A Modern Take on Replicating Viral Vaccines)
Back to TopTop