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Vaccines
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Vaccines for Ebola Virus and Related Diseases
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Vaccines for Ebola Virus and Related Diseases

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

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 27887

Special Issue Editor

Dr. David A. Schwartz

E-Mail Website
Guest Editor
Perinatal Pathology Consulting, Atlanta, GA, USA
Interests: perinatal, placental and obstetrical pathology; emerging infectious diseases; global maternal & child health; tropical medicine; pregnancy complications; stillbirth; maternal and infant mortality; medical epidemiology; medical anthropology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I am pleased to invite you to prepare a contribution to our upcoming special issue on vaccines for Ebola virus disease (EVD) and related diseases. EVD is an important disease in sub-Saharan Africa, reaching its historic clinical impact during 2013-2016 West Africa epidemic. During that time a recombinant vaccine against EVD, the rVSV-ZEBOV vaccine, underwent clinical study including multiple phase I–III human clinical trials to evaluate the safety and efficacy of the vaccine. Following that epidemic, additional EVD outbreaks occurred in 2018 in DR Congo in Équateur province in May and in Kivu province in August, during which the rVSV-ZEBOV vaccine was used in extensive ring vaccination programs. The Kivu EVD outbreak is still continuing and is now the 2nd largest Ebola outbreak in history. Beginning in November 2019 distribution of a 2nd vaccine - the adenovirus 26 vectored glycoprotein/MVA-BN-Filo (Ad26.ZEBOV/MVA-BN) vaccine regimen - was initiated in the DR Congo. Between 8 August 2018 and 4 January 2020 there have been 261,027 persons vaccinated with the rVSV-ZEBOV vaccine; as of 2 December 2019 there have been 4,551 persons vaccinated with Ad26.ZEBOV/MVA-BN-Filo. Data are being collected on the aspects of safety and efficacy of these vaccines, their outcomes when administered to pregnant and lactating women and children, and their effectiveness in protecting against other viruses. As of October 2019, there are 8 vaccines undergoing clinical evaluation – a partial list includes EpivacEbola, Ad5-EBOV, ChAd3, GamEvac Combi and GamEvac Lyo.

This topical issue of Vaccines welcomes contributions dealing with all aspects of the design, development, testing and adminsitration of current and future vaccines for Ebola virus and related viruses including Marburg virus. We also welcome contributions dealing with Ebola vaccine policy and social issues relating to accessibility of vaccines, Ebola vaccine use during humanitarian crises, epidemiological methods for assessing Ebola vaccine efficacy and safety, preventive and reactive uses of the vaccine, vaccine distribution, vaccination of special groups including pregnant women, infants and children and persons with simultaneous co-infections, vaccines and sexual transmission, Ebola vaccine hesitancy, and other important topics relating to these life-saving vaccines.

Prof. David A. Schwartz
Guest Editor

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

  • Ebola virus disease
  • Ebola vaccine
  • rVSV-ZEBOV
  • Ad26.ZEBOV/MVA-BN-Filo
  • vaccine development
  • vaccine complications
  • DR Congo
  • West Africa epidemic
  • Kivu epidemic
  • Équateur epidemic
  • pregnancy and vaccines

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Published Papers (6 papers)

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Research

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14 pages, 262 KiB  
Article
Botched Ebola Vaccine Trials in Ghana: An Analysis of Discourses in the Media
by Esi E. Thompson
Vaccines 2021, 9(2), 177; https://doi.org/10.3390/vaccines9020177 - 19 Feb 2021
Cited by 7 | Viewed by 2450
Abstract
In June 2015, proposed Ebola vaccine trials were suspended by the Ministry of Health of Ghana amid protests from members of parliament and the general public. Scholarship has often focused on the design, development, and administration of vaccines. Of equal importance are the [...] Read more.
In June 2015, proposed Ebola vaccine trials were suspended by the Ministry of Health of Ghana amid protests from members of parliament and the general public. Scholarship has often focused on the design, development, and administration of vaccines. Of equal importance are the social issues surrounding challenges with vaccine trials and their implementation. The purpose of this study was to analyze discourses in the media that led to the suspension of the 2015 Ebola vaccine trials in Ghana. I use a sociological lens drawing on moral panic and risk society theories. The study qualitatively analyzed discourses in 18 semi-structured interviews with media workers, selected online publications, and user comments about the Ebola vaccine trials. The findings show that discourses surrounding the Ebola vaccine trials drew on cultural, biomedical, historical, and even contextual knowledge and circumstances to concretize risk discourses and garner support for their positions. Historical, political, and cultural underpinnings have a strong influence on biomedical practices and how they are (not) accepted. This study highlights the complexity and challenges of undertaking much needed vaccine tests in societies where the notion of drug trials has underlying historical and sociological baggage that determine whether (or not) the trials proceed. Full article
(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)
15 pages, 2303 KiB  
Article
Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine
by Francesco Santoro, Alessia Donato, Simone Lucchesi, Sara Sorgi, Alice Gerlini, Marielle C. Haks, Tom H. M. Ottenhoff, Patricia Gonzalez-Dias, VSV-EBOVAC Consortium, VSV-EBOPLUS Consortium, Helder I. Nakaya, Angela Huttner, Claire-Anne Siegrist, Donata Medaglini and Gianni Pozzi
Vaccines 2021, 9(2), 67; https://doi.org/10.3390/vaccines9020067 - 20 Jan 2021
Cited by 12 | Viewed by 3646
Abstract
Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo®), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the [...] Read more.
Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo®), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. A global transcriptomic approach was used to profile the blood host-response in 51 healthy volunteers enrolled in a phase 1/2 clinical trial. Signatures of the host responses were investigated assessing the enrichment in differentially expressed genes (DEGs) of specific “blood transcription modules” (BTM). Comparison of gene-expression levels showed that vaccination produces a peak of 5469 DEGs at day one, representing 38.6% of the expressed genes. Out of 346 BTMs, 144 were significantly affected by vaccination. Innate immunity pathways were induced from day 1 to day 14. At days 2 and 3, neutrophil modules were downregulated and complement-related modules upregulated. T-cell and cell-cycle associated modules were upregulated at days 7 and 14, while at day 28, no modules remained activated. At day 14, a direct correlation was observed between ZEBOV glycoprotein-specific antibody titres and activation of seven BTMs, including two related to B-cell activation and B cell receptor signalling. Transcriptomic analysis identified an rVSVΔG-ZEBOV-GP-induced signature and demonstrated a direct correlation of blood transcriptomic changes with ZEBOV glycoprotein-specific antibody titres. Full article
(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)
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14 pages, 2956 KiB  
Article
Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen
by Larisa I. Karpenko, Evgeny K. Apartsin, Sergei G. Dudko, Ekaterina V. Starostina, Olga N. Kaplina, Denis V. Antonets, Ekaterina A. Volosnikova, Boris N. Zaitsev, Anastasiya Yu. Bakulina, Aliya G. Venyaminova, Alexander A. Ilyichev and Sergei I. Bazhan
Vaccines 2020, 8(4), 718; https://doi.org/10.3390/vaccines8040718 - 1 Dec 2020
Cited by 24 | Viewed by 2818
Abstract
Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers [...] Read more.
Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers (PAMAM G4) and a polyglucin:spermidine conjugate (PG). Methods: Optimal conditions were selected for obtaining complexes of previously developed DNA vaccines with cationic polymers. The sizes, mobility and surface charge of the complexes with PG and PAMAM 4G have been determined. The immunogenicity of the obtained vaccine constructs was investigated in BALB/c mice. Results: It was shown that packaging of DNA vaccine constructs both in the PG envelope and the PAMAM 4G envelope results in an increase in their immunogenicity as compared with the group of mice immunized with the of vector plasmid pcDNA3.1 (a negative control). The highest T-cell responses were shown in mice immunized with complexes of DNA vaccines with PG and these responses significantly exceeded those in the groups of animals immunized with both the combination of naked DNAs and the combination DNAs coated with PAMAM 4G. In the group of animals immunized with complexes of the DNA vaccines with PAMAM 4G, no statistical differences were found in the ability to induce T-cell responses, as compared with the group of mice immunized with the combination of naked DNAs. Conclusions: The PG conjugate can be considered as a promising and safe means to deliver DNA-based vaccines. The use of PAMAM requires further optimization. Full article
(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)
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17 pages, 2175 KiB  
Article
A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector
by Sarah Sebastian, Amy Flaxman, Kuan M. Cha, Marta Ulaszewska, Ciaran Gilbride, Hannah Sharpe, Edward Wright, Alexandra J. Spencer, Stuart Dowall, Roger Hewson, Sarah Gilbert and Teresa Lambe
Vaccines 2020, 8(2), 241; https://doi.org/10.3390/vaccines8020241 - 21 May 2020
Cited by 11 | Viewed by 4778
Abstract
In the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field of [...] Read more.
In the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field of vaccine development, in which broadly protective vaccines represent an unmet need. This is particularly evident for filoviruses, as there are multiple family members that can cause lethal haemorrhagic fever, including Zaire ebolavirus, Sudan ebolavirus, and Marburg virus. In an attempt to address this need, both pre-clinical and clinical studies previously used mixed or co-administered monovalent vaccines to prevent filovirus mediated disease. However, these multi-vaccine and multi-dose vaccination regimens do not represent a practical immunisation scheme when considering the target endemic areas. We describe here the development of a single multi-pathogen filovirus vaccine candidate based on a replication-deficient simian adenoviral vector. Our vaccine candidate encodes three different filovirus glycoproteins in one vector and induces strong cellular and humoral immunity to all three viral glycoproteins after a single vaccination. Crucially, it was found to be protective in a stringent Zaire ebolavirus challenge in guinea pigs in a one-shot vaccination regimen. This trivalent filovirus vaccine offers a tenable vaccine product that could be rapidly translated to the clinic to prevent filovirus-mediated viral haemorrhagic fever. Full article
(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)
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Review

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23 pages, 2774 KiB  
Review
Environmental Risk Assessment for rVSVΔG-ZEBOV-GP, a Genetically Modified Live Vaccine for Ebola Virus Disease
by Joan G. Tell, Beth-Ann G. Coller, Sheri A. Dubey, Ursula Jenal, William Lapps, Liman Wang and Jayanthi Wolf
Vaccines 2020, 8(4), 779; https://doi.org/10.3390/vaccines8040779 - 19 Dec 2020
Cited by 11 | Viewed by 5309
Abstract
rVSVΔG-ZEBOV-GP is a live, attenuated, recombinant vesicular stomatitis virus (rVSV)-based vaccine for the prevention of Ebola virus disease caused by Zaire ebolavirus. As a replication-competent genetically modified organism, rVSVΔG-ZEBOV-GP underwent various environmental evaluations prior to approval, the most in-depth being the environmental [...] Read more.
rVSVΔG-ZEBOV-GP is a live, attenuated, recombinant vesicular stomatitis virus (rVSV)-based vaccine for the prevention of Ebola virus disease caused by Zaire ebolavirus. As a replication-competent genetically modified organism, rVSVΔG-ZEBOV-GP underwent various environmental evaluations prior to approval, the most in-depth being the environmental risk assessment (ERA) required by the European Medicines Agency. This ERA, as well as the underlying methodology used to arrive at a sound conclusion about the environmental risks of rVSVΔG-ZEBOV-GP, are described in this review. Clinical data from vaccinated adults demonstrated only infrequent, low-level shedding and transient, low-level viremia, indicating a low person-to-person infection risk. Animal data suggest that it is highly unlikely that vaccinated individuals would infect animals with recombinant virus vaccine or that rVSVΔG-ZEBOV-GP would spread within animal populations. Preclinical studies in various hematophagous insect vectors showed that these species were unable to transmit rVSVΔG-ZEBOV-GP. Pathogenicity risk in humans and animals was found to be low, based on clinical and preclinical data. The overall risk for non-vaccinated individuals and the environment is thus negligible and can be minimized further through defined mitigation strategies. This ERA and the experience gained are relevant to developing other rVSV-based vaccines, including candidates under investigation for prevention of COVID-19. Full article
(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)
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Other

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18 pages, 2421 KiB  
Perspective
Being Pregnant during the Kivu Ebola Virus Outbreak in DR Congo: The rVSV-ZEBOV Vaccine and Its Accessibility by Mothers and Infants during Humanitarian Crises and in Conflict Areas
by David A. Schwartz
Vaccines 2020, 8(1), 38; https://doi.org/10.3390/vaccines8010038 - 22 Jan 2020
Cited by 35 | Viewed by 7540
Abstract
The Ebola virus disease (EVD) outbreak that began in Kivu province of the Democratic Republic of the Congo (DRC) in July 2018 is the second largest in history. It is also the largest and most deadly of the ten Ebola outbreaks to occur [...] Read more.
The Ebola virus disease (EVD) outbreak that began in Kivu province of the Democratic Republic of the Congo (DRC) in July 2018 is the second largest in history. It is also the largest and most deadly of the ten Ebola outbreaks to occur in DRC, the country where Ebola was first identified during the 1976 Yambuku outbreak. The Kivu region is one of the most challenging locations in which to organize humanitarian assistance. It is an active conflict zone in which numerous armed groups are conducting violent acts, often directed against the inhabitants, healthcare and relief workers and peacekeepers. EVD has been especially problematic in pregnancy—previous outbreaks both in DRC and other countries have resulted in very high mortality rates among pregnant women and especially their infants, with maternal mortality in some outbreaks reaching over 90% and perinatal mortality 100%. The development and implementation of the Merck rVSV-ZEBOV vaccine for Ebola infection has been a tremendous public health advance in preventing EVD, being used successfully in both the West Africa Ebola epidemic and the Équateur DRC Ebola outbreak. But from the start of the Kivu outbreak, policy decisions had resulted in excluding pregnant and lactating women and their infants from receiving it during extensive ring vaccination efforts. In June 2019, this policy was reversed, 10 months after the start of the outbreak. Pregnant and lactating women are now permitted not only the rVSV-ZEBOV vaccine in the continuing Kivu outbreak but also the newly implemented Ad26.ZEBOV/MVA-BN vaccine. Full article
(This article belongs to the Special Issue Vaccines for Ebola Virus and Related Diseases)
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