Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study

Huttner, Angela; Agnandji, Selidji Todagbé; Combescure, Christophe; Fernandes, J.; Bache, Emmanuel B.; Kabwende, Lumeka; Ndungu, Francis M.; Brosnahan, Jessica; Monath, Thomas P.; Lemaître, Barbara; Grillet, Stéphane; Botto, Miriam; Engler, Olivier; Portmann, Jasmine; Siegrist, Denise; Bejon, Philip; Silvera, Peter; Kremsner, Peter G.; Siegrist, Claire‐Anne; Krishna, Sanjeev; Addo, Marylyn M.; Becker, Stephan; Krähling, Verena; Njuguna, Patricia; Kiény, Marie-Paule; Ahmed, Rafi; Anderson, Jenna; Auderset, Floriane; Borgianni, Luisa; Ciabattini, Annalisa; Haks, Mariëlle C.; Harandi, Ali M.; Heppner, D. Gray; Gerlini, Alice; Medaglini, Donata; Ottenhoff, Tom H. M.; Pejoski, David; Page, Mark; Pozzi, Gianni; Santoro, Francesco; Dubey, Sheri; Nakaya, Hidehiko; O’Rourke, Fiona; Rothenberger, Sylvia

doi:10.1016/s1473-3099(18)30165-8

Cited by 66 publications

(47 citation statements)

References 24 publications

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“…Furthermore, we established that the total IgG response to EBOV GP is an im-portant parameter and likely a good correlate of protection for preclinical studies [9] . The clinical trials using the VSV-EBOV Kik vaccine confirmed the importance of the total IgG response to EBOV GP as a likely correlate of protection, but some studies reported dose-dependent GP-specific IgG responses to VSV-EBOV Kik vaccination [15][16][17][18][19] . Interestingly, in the macaque study here we found no such correlation between vaccine dose and total EBOV GP-specific IgG or neutralizing immune responses ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A similar role for GPspecific antibodies was reported from the VSV-EBOV Kik clinical trials making this response a potential correlate of protection in humans [ 14 , 15 ]. Clinical trials also indicated a vaccine dosedependent antibody response which ultimately lead to a recommended dose of 2 × 10 7 plaque forming units (PFU) VSV-EBOV Kik for human use [15][16][17][18][19] . The vaccine dose for ring vaccination in DRC, which had initially been higher, has now also been adjusted to that dose [20] .…”

Section: Introductionmentioning

confidence: 99%

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Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge

et al. 2019

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Background: Ebola virus (EBOV), variant Makona, was the causative agent of the 2013-2016 West African epidemic responsible for almost 30,0 0 0 human infections and over 11,0 0 0 fatalities. During the epidemic, the development of several experimental vaccines was accelerated through human clinical trials. One of them, the vesicular stomatitis virus (VSV)-based vaccine VSV-EBOV, showed promising efficacy in a phase 3 clinical trial in Guinea and is currently used in the ongoing EBOV outbreak in the northeastern part of the Democratic Republic of the Congo (DRC). This vaccine expresses the EBOV-Kikwit glycoprotein from the 1995 outbreak as the immunogen. Methods: Here we generated a VSV-based vaccine expressing the contemporary EBOV-Makona glycoprotein. We characterized the vaccine in tissue culture and analyzed vaccine efficacy in the cynomolgus macaque model. Subsequently, we determined the dose-dependent protective efficacy in nonhuman primates against lethal EBOV challenge. Findings: We observed complete protection from disease with VSV-EBOV doses ranging from 1 × 10 7 to 1 × 10 1 plaque-forming units. Some protected animals receiving lower vaccine doses developed temporary low-level EBOV viremia. Control animals developed classical EBOV disease and reached euthanasia criteria within a week after challenge. This study demonstrates that very low doses of VSV-EBOV uniformly protect macaques against lethal EBOV challenge. Interpretation: Our study provides missing pre-clinical data supporting the use of reduced VSV-EBOV vaccine doses without decreasing protective efficacy and at the same time increase vaccine safety and availability-two critical concerns in public health response.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge

et al. 2019

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“…39 It was also observed that its development correlated with higher vaccine efficacy. 40 Three affected participants also developed rVSV-PCR positive skin lesions, with infectious rVSV recovered from one participant. After the study halt, simultaneously running phase I studies of VSV-EBOV included arthralgia/arthritis as a solicited adverse event, but while transient arthralgia was likewise reported, the high frequency of arthritis cases was not observed to the same extent.…”

Section: Safety Datamentioning

confidence: 96%

“…Antibody responses developed at 14 days p.v., peaked around day 28 and remained detectable for at least 2 years. 28,29,40 Besides evaluating humoral responses, clinical trials also evaluated all other arms of immune responses. One study focused on T follicular helper (TFH) cells and observed a correlation with antibody titers.…”

Section: Correlates Of Protection and Duration Of Immune Responsesmentioning

confidence: 99%

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi

Dahlke

Addo

2019

Human Vaccines & Immunotherapeutics

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The devastating Ebola virus (EBOV) outbreak in West Africa in 2013-2016 has flagged the need for the timely development of vaccines for high-threat pathogens. To be better prepared for new epidemics, the WHO has compiled a list of priority pathogens that are likely to cause future outbreaks and for which R&D efforts are, therefore, paramount (R&D Blueprint: https://www.who.int/blueprint/priority-diseases/en/). To this end, the detailed characterization of vaccine platforms is needed. The vesicular stomatitis virus (VSV) has been established as a robust vaccine vector backbone for infectious diseases for well over a decade. The recent clinical trials testing the vaccine candidate VSV-EBOV against EBOV disease now have added a substantial amount of clinical data and suggest VSV to be an ideal vaccine vector candidate for outbreak pathogens. In this review, we discuss insights gained from the clinical VSV-EBOV vaccine trials as well as from animal studies investigating vaccine candidates for Blueprint pathogens. ARTICLE HISTORY

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“…Collectively, trial data indicate that the rVSV-ZEBOV vaccine has an acceptable safety profile, and that it induces immunity that is durable for at least 24 months in adults (antibody responses for 89–100% of recipients depending on the doses administered). 12 Vaccination strategies involving rVSV-ZEBOV, although not yet licensed, are now used during epidemics through emergency authorisation. During May and June of 2018, more than 3000 individuals were vaccinated in the Democratic Republic of the Congo as part of the WHO response to the Ebola virus disease outbreak, according to the country’s Ministry of Health.…”

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confidence: 99%

Prevention of Ebola virus disease through vaccination: where we are in 2018

et al. 2018

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Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study

Abstract: The Wellcome Trust and Innovative Medicines Initiative 2 Joint Undertaking.

Cited by 66 publications

References 24 publications

Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge

Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Prevention of Ebola virus disease through vaccination: where we are in 2018

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