Vectored 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 March 2021) | Viewed by 60311

Special Issue Editors


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Guest Editor
Department of Bioengineering, McGill University, Montreal, QC H2X 1Y4, Canada
Interests: cell culture engineering; bioprocess optimization and scale-up; process analytical technologies and process control; viral vaccines manufacturing; viral vectors and nanoparticules for gene delivery and vaccination
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Co-Guest Editor
Department of Chemical Engineering, Polytechnique Montréal, Montréal, QC, Canada
Interests: recombinant proteins; viral vectors; vaccines; animal cell culture; bioprocess development, optimization and control
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vectored vaccines reached important milestones in term of safety and efficacy over the last decade. With the FDA approval in December 2019 of Erbevo, a recombinant Vesicular Stomatis Virus-Vectored vaccine against Zaire Ebola Virus infection and China FDA approval in October 2017 of an Adenovirus-vectored Ebola vaccine established the regulatory baselines of two important recombinant vaccination platforms. Whereas, HIV-Canarypox vector has been used over many years in the RV144 phase-3 efficacy trial and other vectors have been evaluated in the clinic. Remarkably, on the WHO novel coronavirus-landscape-covid-19 list (July 20, 2020) among the 24 candidate vaccines in clinical evaluations, 19 candidate vaccines are recombinant and 3 are replication defective adeno-vectored vaccines. Many more vectored vaccines (15%) are evaluated within the current preclinical studies of 142 candidate vaccines. This is a strong indication of the flexibility and robustness of these technology platforms.

This special issue will focus on bringing forward the most advanced research and development work on vectored vaccines from antigen design, immunogenicity, protection, manufacturing and delivery. Articles bringing novel perspectives on this broad topic are also welcome including recombinant viral vectors developed as immunotherapeutics or therapeutic vaccines.

Prof. Dr. Amine A. Kamen
Prof. Olivier Henry
Guest Editors

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Keywords

  • Viral vectors
  • viral infections
  • recombinant viral vaccines
  • antigen design
  • vaccination platforms
  • vaccine production
  • delivery

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Published Papers (10 papers)

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Editorial

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3 pages, 164 KiB  
Editorial
Vectored-Vaccine Platforms Enabled Rapid Development of Safe and Effective Vaccines in Response to COVID-19 Pandemic Situation
by Amine A. Kamen
Vaccines 2021, 9(7), 722; https://doi.org/10.3390/vaccines9070722 - 2 Jul 2021
Cited by 1 | Viewed by 2329
Abstract
In 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), caused an ongoing public health crisis [...] Full article
(This article belongs to the Special Issue Vectored Vaccines)

Research

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12 pages, 2979 KiB  
Article
The Safe Baculovirus-Based PrM/E DNA Vaccine Protected Fetuses against Zika Virus in A129 Mice
by Hanul Choi, Jungmin Chun, Mina Park, Suyeon Kim, Nahyun Kim, Hee-Jung Lee, Minjee Kim, Ha Youn Shin, Yu-Kyoung Oh and Young Bong Kim
Vaccines 2021, 9(5), 438; https://doi.org/10.3390/vaccines9050438 - 30 Apr 2021
Cited by 3 | Viewed by 2968
Abstract
The Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family of enveloped RNA viruses. The correlation between viral infection and fetal microcephaly was revealed in 2015, yet we still lack a vaccine against ZIKV. Here, we present a genetic vaccine that [...] Read more.
The Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family of enveloped RNA viruses. The correlation between viral infection and fetal microcephaly was revealed in 2015, yet we still lack a vaccine against ZIKV. Here, we present a genetic vaccine that delivers the premembrane (prM) and envelope (E) genes of ZIKV using a recombinant baculovirus vector that expresses a human endogenous retrovirus (HERV) envelope on its surface to enhance gene delivery. We observed that baculoviruses with HERV envelopes (AcHERV) exhibited specifically higher gene transfer efficiency in human cells compared to the wild-type baculovirus vector. Using the AcHERV baculovirus vector, we constructed a recombinant baculovirus vaccine encoding ZIKV prM/E genes (AcHERV-ZIKV), which are major targets of neutralizing antibodies. Mice immunized twice with AcHERV-ZIKV exhibited high levels of IgG, neutralizing antibodies, and IFN-γ. In challenge tests in IFN knock-out mice (A129), AcHERV-ZIKV showed complete protection in both challenge and pregnancy tests. These results suggest that AcHERV-ZIKV could be a potential vaccine candidate for human application. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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13 pages, 3131 KiB  
Article
Chimeric Measles Virus (MV/RSV), Having Ectodomains of Respiratory Syncytial Virus (RSV) F and G Proteins Instead of Measles Envelope Proteins, Induced Protective Antibodies against RSV
by Akihito Sawada, Takashi Ito, Yoshiaki Yamaji and Tetsuo Nakayama
Vaccines 2021, 9(2), 156; https://doi.org/10.3390/vaccines9020156 - 16 Feb 2021
Cited by 3 | Viewed by 3209
Abstract
In our previous study, fusion (F) or glyco (G) protein coding sequence of respiratory syncytial virus (RSV) was inserted at the P/M junction of the measles AIK-C vector (MVAIK), and the recombinant measles virus induced protective immune responses. In the present study, the [...] Read more.
In our previous study, fusion (F) or glyco (G) protein coding sequence of respiratory syncytial virus (RSV) was inserted at the P/M junction of the measles AIK-C vector (MVAIK), and the recombinant measles virus induced protective immune responses. In the present study, the ectodomains of measles fusion (F) and hemagglutinin (HA) proteins were replaced with those of RSV F and G proteins, and a chimeric MV/RSV vaccine was developed. It expressed F and G proteins of RSV and induced cytopathic effect (CPE) in epithelial cell lines (Vero, A549, and HEp-2 cells), but not in lymphoid cell lines (B95a, Jurkat, and U937 cells). A chimeric MV/RSV grew similarly to AIK-C with no virus growth at 39 °C. It induced NT antibodies against RSV in cotton rats three weeks after immunization through intramuscular route and enhanced response was observed after the second dose at eight weeks. After the RSV challenge with 106 PFU, significantly lower virus (101.4±0.1 PFU of RSV) was recovered from lung tissue in the chimeric MV/RSV vaccine group than in the MVAIK control group with 104.6±0.2 PFU (p < 0.001) and no obvious inflammatory pathological finding was noted. The strategy of ectodomain replacement in the measles virus vector is expected to lead to the development of safe and effective vaccines for other enveloped viruses. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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15 pages, 1827 KiB  
Article
Optimising Vaccine Dose in Inoculation against SARS-CoV-2, a Multi-Factor Optimisation Modelling Study to Maximise Vaccine Safety and Efficacy
by John Benest, Sophie Rhodes, Matthew Quaife, Thomas G. Evans and Richard G. White
Vaccines 2021, 9(2), 78; https://doi.org/10.3390/vaccines9020078 - 22 Jan 2021
Cited by 15 | Viewed by 4448
Abstract
Developing a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to published dose-dependent seroconversion and adverse event [...] Read more.
Developing a vaccine against the global pandemic SARS-CoV-2 is a critical area of active research. Modelling can be used to identify optimal vaccine dosing; maximising vaccine efficacy and safety and minimising cost. We calibrated statistical models to published dose-dependent seroconversion and adverse event data of a recombinant adenovirus type-5 (Ad5) SARS-CoV-2 vaccine given at doses 5.0 × 1010, 1.0 × 1011 and 1.5 × 1011 viral particles. We estimated the optimal dose for three objectives, finding: (A) the minimum dose that may induce herd immunity, (B) the dose that maximises immunogenicity and safety and (C) the dose that maximises immunogenicity and safety whilst minimising cost. Results suggest optimal dose [95% confidence interval] in viral particles per person was (A) 1.3 × 1011 [0.8–7.9 × 1011], (B) 1.5 × 1011 [0.3–5.0 × 1011] and (C) 1.1 × 1011 [0.2–1.5 × 1011]. Optimal dose exceeded 5.0 × 1010 viral particles only if the cost of delivery exceeded £0.65 or cost per 1011 viral particles was less than £6.23. Optimal dose may differ depending on the objectives of developers and policy-makers, but further research is required to improve the accuracy of optimal-dose estimates. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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30 pages, 7065 KiB  
Article
BoHV-1-Vectored BVDV-2 Subunit Vaccine Induces BVDV Cross-Reactive Cellular Immune Responses and Protects against BVDV-2 Challenge
by Shafiqul I. Chowdhury, Katrin Pannhorst, Neha Sangewar, Selvaraj Pavulraj, Xue Wen, Rhett W. Stout, Waithaka Mwangi and Daniel B. Paulsen
Vaccines 2021, 9(1), 46; https://doi.org/10.3390/vaccines9010046 - 13 Jan 2021
Cited by 19 | Viewed by 5682
Abstract
The bovine respiratory disease complex (BRDC) remains a major problem for both beef and dairy cattle industries worldwide. BRDC frequently involves an initial viral respiratory infection resulting in immunosuppression, which creates a favorable condition for fatal secondary bacterial infection. Current polyvalent modified live [...] Read more.
The bovine respiratory disease complex (BRDC) remains a major problem for both beef and dairy cattle industries worldwide. BRDC frequently involves an initial viral respiratory infection resulting in immunosuppression, which creates a favorable condition for fatal secondary bacterial infection. Current polyvalent modified live vaccines against bovine herpesvirus type 1(BoHV-1) and bovine viral diarrhea virus (BVDV) have limitations concerning their safety and efficacy. To address these shortcomings and safety issues, we have constructed a quadruple gene mutated BoHV-1 vaccine vector (BoHV-1 QMV), which expresses BVDV type 2, chimeric E2 and Flag-tagged Erns-fused with bovine granulocyte monocyte colony-stimulating factor (GM-CSF) designated here as QMV-BVD2*. Here we compared the safety, immunogenicity, and protective efficacy of QMV-BVD2* vaccination in calves against BVDV-2 with Zoetis Bovi-shield Gold 3 trivalent (BoHV-1, BVDV types 1 and 2) vaccine. The QMV-BVD2* prototype subunit vaccine induced the BoHV-1 and BVDV-2 neutralizing antibody responses along with BVDV-1 and -2 cross-reactive cellular immune responses. Moreover, after a virulent BVDV-2 challenge, the QMV-BVD2* prototype subunit vaccine conferred a more rapid recall BVDV-2-specific neutralizing antibody response and considerably better recall BVDV types 1 and 2-cross protective cellular immune responses than that of the Zoetis Bovi-shield Gold 3. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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14 pages, 1918 KiB  
Article
A Newcastle Disease Virus (NDV) Expressing a Membrane-Anchored Spike as a Cost-Effective Inactivated SARS-CoV-2 Vaccine
by Weina Sun, Stephen McCroskery, Wen-Chun Liu, Sarah R. Leist, Yonghong Liu, Randy A. Albrecht, Stefan Slamanig, Justine Oliva, Fatima Amanat, Alexandra Schäfer, Kenneth H. Dinnon III, Bruce L. Innis, Adolfo García-Sastre, Florian Krammer, Ralph S. Baric and Peter Palese
Vaccines 2020, 8(4), 771; https://doi.org/10.3390/vaccines8040771 - 17 Dec 2020
Cited by 59 | Viewed by 14205
Abstract
A successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine must not only be safe and protective, but must also meet the demand on a global scale at a low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based [...] Read more.
A successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine must not only be safe and protective, but must also meet the demand on a global scale at a low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent coronavirus disease 2019 (COVID-19) vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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20 pages, 2737 KiB  
Article
Rapid High-Yield Production of Functional SARS-CoV-2 Receptor Binding Domain by Viral and Non-Viral Transient Expression for Pre-Clinical Evaluation
by Omar Farnós, Alina Venereo-Sánchez, Xingge Xu, Cindy Chan, Shantoshini Dash, Hanan Chaabane, Janelle Sauvageau, Fouad Brahimi, Uri Saragovi, Denis Leclerc and Amine A. Kamen
Vaccines 2020, 8(4), 654; https://doi.org/10.3390/vaccines8040654 - 4 Nov 2020
Cited by 28 | Viewed by 5804
Abstract
Vaccine design strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the Spike protein or its subunits as the main antigen target of neutralizing antibodies. In this work, we propose rapid production methods of an extended segment of the Spike [...] Read more.
Vaccine design strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are focused on the Spike protein or its subunits as the main antigen target of neutralizing antibodies. In this work, we propose rapid production methods of an extended segment of the Spike Receptor Binding Domain (RBD) in HEK293SF cells cultured in suspension, in serum-free media, as a major component of a COVID-19 subunit vaccine under development. The expression of RBD, engineered with a sortase-recognition motif for protein-based carrier coupling, was achieved at high yields by plasmid transient transfection or human type-5-adenoviral infection of the cells, in a period of only two and three weeks, respectively. Both production methods were evaluated in 3L-controlled bioreactors with upstream and downstream bioprocess improvements, resulting in a product recovery with over 95% purity. Adenoviral infection led to over 100 µg/mL of RBD in culture supernatants, which was around 7-fold higher than levels obtained in transfected cultures. The monosaccharide and sialic acid content was similar in the RBD protein from the two production approaches. It also exhibited a proper conformational structure as recognized by monoclonal antibodies directed against key native Spike epitopes. Efficient direct binding to ACE2 was also demonstrated at similar levels in RBD obtained from both methods and from different production lots. Overall, we provide bioprocess-related data for the rapid, scalable manufacturing of low cost RBD based vaccines against SARS-CoV-2, with the added value of making a functional antigen available to support further research on uncovering mechanisms of virus binding and entry as well as screening for potential COVID-19 therapeutics. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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16 pages, 2711 KiB  
Article
A Scalable Topical Vectored Vaccine Candidate against SARS-CoV-2
by Mohammed A. Rohaim and Muhammad Munir
Vaccines 2020, 8(3), 472; https://doi.org/10.3390/vaccines8030472 - 24 Aug 2020
Cited by 19 | Viewed by 5548
Abstract
The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of a SARS-CoV-2 vaccine which would [...] Read more.
The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of a SARS-CoV-2 vaccine which would be safe, efficacious and scalable. Owing to unavailability of the vaccine, we propose a de novo synthesized avian orthoavulavirus 1 (AOaV-1)-based topical respiratory vaccine candidate against CoVID-19. Avirulent strain of AOaV-1 was engineered to express full length spike (S) glycoprotein which is highly neutralizing and a major protective antigen of the SARS-CoV-2. Broad-scale in vitro characterization of a recombinant vaccine candidate demonstrated efficient co-expression of the hemagglutinin-neuraminidase (HN) of AOaV-1 and S protein of SARS-CoV-2, and comparable replication kinetics were observed in a cell culture model. The recombinant vaccine candidate virus actively replicated and spread within cells independently of exogenous trypsin. Interestingly, incorporation of S protein of SARS-CoV-2 into the recombinant AOaV-1 particles attributed the sensitivity to anti-SARS-CoV-2 antiserum and more prominently to anti-AOaV-1 antiserum. Finally, our results demonstrated that the recombinant vaccine vector stably expressed S protein after multiple propagations in chicken embryonated eggs, and this expression did not significantly impact the in vitro growth characteristics of the recombinant. Taken together, the presented respiratory vaccine candidate is highly attenuated in primates per se, safe and lacking pre-existing immunity in human, and carries the potential for accelerated vaccine development against CoVID-19 for clinical studies. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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Review

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20 pages, 356 KiB  
Review
Environmental Risk Assessment of Recombinant Viral Vector Vaccines against SARS-Cov-2
by Aline Baldo, Amaya Leunda, Nicolas Willemarck and Katia Pauwels
Vaccines 2021, 9(5), 453; https://doi.org/10.3390/vaccines9050453 - 3 May 2021
Cited by 14 | Viewed by 9505
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Over the past months, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Various platforms are being used for [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Over the past months, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Various platforms are being used for the development of COVID-19 vaccine candidates: recombinant viral vectors, protein-based vaccines, nucleic acid-based vaccines, and inactivated/attenuated virus. Recombinant viral vector vaccine candidates represent a significant part of those vaccine candidates in clinical development, with two already authorised for use in the European Union and one currently under rolling review by the European Medicines Agency (EMA). Since recombinant viral vector vaccine candidates are considered as genetically modified organisms (GMOs), their regulatory oversight includes besides an assessment of their quality, safety and efficacy, also an environmental risk assessment (ERA). The present article highlights the main characteristics of recombinant viral vector vaccine (candidates) against SARS-CoV-2 in the pipeline and discusses their features from an environmental risk point of view. Full article
(This article belongs to the Special Issue Vectored Vaccines)

Other

8 pages, 1494 KiB  
Brief Report
Safety and Immunogenicity of Adenovirus and Poxvirus Vectored Vaccines against a Mycobacterium Avium Complex Subspecies
by Pedro M. Folegatti, Amy Flaxman, Daniel Jenkin, Rebecca Makinson, Lucy Kingham-Page, Duncan Bellamy, Fernando Ramos Lopez, Jonathan Sheridan, Ian Poulton, Jeremy Aboagye, Nguyen Tran, Celia Mitton, Rachel Roberts, Alison M. Lawrie, Adrian V. S. Hill, Katie J. Ewer and Sarah Gilbert
Vaccines 2021, 9(3), 262; https://doi.org/10.3390/vaccines9030262 - 16 Mar 2021
Cited by 2 | Viewed by 5219
Abstract
Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four Mycobacterium avium subspecies paratuberculosis antigens as a single dose or as [...] Read more.
Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four Mycobacterium avium subspecies paratuberculosis antigens as a single dose or as a booster vaccine following a simian adenovirus (ChAdOx2) prime. We demonstrate that a heterologous prime-boost schedule is well tolerated and induced T-cell immune responses. Full article
(This article belongs to the Special Issue Vectored Vaccines)
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