Editorial

3 pages, 164 KiB

Open AccessEditorial

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 - 02 Jul 2021

Cited by 1 | Viewed by 2044

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

Open AccessArticle

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 2491

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

Open AccessArticle

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 2722

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 (10^1.4±0.1 PFU of RSV) was recovered from lung tissue in the chimeric MV/RSV vaccine group than in the MVAIK control group with 10^4.6±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

Open AccessArticle

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 3957

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

Open AccessArticle

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 16 | Viewed by 4852

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

Open AccessArticle

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 55 | Viewed by 13176

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

Open AccessArticle

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 - 04 Nov 2020

Cited by 27 | Viewed by 5040

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

Open AccessArticle

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 18 | Viewed by 5070

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

Open AccessReview

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 - 03 May 2021

Cited by 11 | Viewed by 8174

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

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8 pages, 1494 KiB

Open AccessBrief 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 4838

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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