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Safety and immunogenicity of a next-generation live-attenuated yellow fever vaccine produced in a Vero cell line in the USA: a phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial.
Modjarrad, Kayvon; Scott, Paul T; McCauley, Melanie; Ober-Shepherd, Brittany; Sondergaard, Erica; Amare, Mihret F; Parikh, Ajay P; Omar, Badryah; Minutello, Ada-Marie; Adhikarla, Haritha; Wu, Yukun; P, Andrey Rojas; Delore, Valentine; Mantel, Nathalie; Morrison, Meshell N; Kourbanova, Kamila S; Martinez, Melissa E; Guzman, Ivelese; Greenleaf, Melissa E; Darden, Janice M; Koren, Michael A; Hamer, Melinda J; Lee, Christine E; Hutter, Jack N; Peel, Sheila A; Robb, Merlin L; Vangelisti, Manuel; Feroldi, Emmanuel.
Afiliação
  • Modjarrad K; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Scott PT; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • McCauley M; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Ober-Shepherd B; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Sondergaard E; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Amare MF; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Parikh AP; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Omar B; Emerging Infectious Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Minutello AM; Sanofi, Marcy L'Etoile, France.
  • Adhikarla H; Sanofi, Swiftwater, PA, USA.
  • Wu Y; Sanofi, Swiftwater, PA, USA.
  • P AR; Sanofi, Bogotá, Colombia.
  • Delore V; Sanofi, Marcy L'Etoile, France.
  • Mantel N; Sanofi, Marcy L'Etoile, France.
  • Morrison MN; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Kourbanova KS; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Martinez ME; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Guzman I; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Greenleaf ME; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Darden JM; Diagnostics and Countermeasures Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Koren MA; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Hamer MJ; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA; Department of Military and Emergency Medicine, Uniformed Services University, Bethesda, MD, USA; Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, U
  • Lee CE; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Hutter JN; Clinical Trials Center, Walter Reed Army Institute of Research, Bethesda, MD, USA.
  • Peel SA; Diagnostics and Countermeasures Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Robb ML; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Vangelisti M; Sanofi, Marcy L'Etoile, France.
  • Feroldi E; Sanofi, Marcy L'Etoile, France. Electronic address: emmanuel.feroldi@sanofi.com.
Lancet Infect Dis ; 2024 Aug 14.
Article em En | MEDLINE | ID: mdl-39153488
ABSTRACT

BACKGROUND:

Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies. In this study, we aimed to report the safety and immunogenicity of vYF in human clinical trial participants.

METHODS:

In this first in-human, phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial conducted at a single centre in the USA (Walter Reed Army Institute of Research, Silver Spring, MD, USA), 72 healthy adults (aged 18-60 years), without a known history of flavivirus infection or vaccination were randomly assigned (1111) using interactive response technology to receive one dose of either vYF at 4, 5 or 6 Log CCID50 or the licensed YF-VAX (18 individuals per group). The primary outcomes were safety, neutralising antibody (NAb) titres through D180 post-vaccination in the per-protocol analysis set (comprised of yellow fever-naive participants who received their intended vaccine and provided a valid post-vaccination blood sample), and occurrence, and level of yellow fever viraemia in each vaccine group through D14 post-vaccination.

FINDINGS:

All vYF doses had a safety and tolerability profile similar to YF-VAX. The most frequently reported solicited injection site reactions (vYF groups vs YF-VAX group) were pain (22% [12 of 54 participants, 95% CI 12-36] vs 28% [five of 18 participants, 10-54]), and erythema (13% [seven of 54 participants, 5-25] vs 39% [seven of 18 participants, 17-64]), with headache (32% [17 of 54 participants, 20-46] vs 44% [eight of 18 participants, 22-69]) and malaise (26% [14 of 54 participants, 15-40] vs 33% [six of 18 participants, 13-59]) as the most frequently reported solicited systemic reactions. One grade 3 solicited reaction (erythema) reported in the YF-VAX group resolved spontaneously. No serious unsolicited adverse events or deaths were reported. Viraemia was transiently detected in 50 participants between D4 and D10 in all groups and was observed in more participants or for a longer time in the vYF 6 Log CCID50 and YF-VAX groups. All yellow fever-naive vaccine recipients across the study groups seroconverted yielding four-fold increase from baseline in yellow fever NAb titres measured by yellow fever microneutralisation assay by D28 and were seroprotected with yellow fever NAb titres of at least 10 [1/dil]). Overall, 100% (18 of 18 participants, 95% CI 82-100), 89% (16 participants, 65-99), 100% (18 participants, 82-100), and 94% (17 participants, 73-100) of participants in the vYF 4 Log, vYF 5 Log, vYF 6 Log CCID50 groups, and YF-VAX group, respectively, remained seroprotected through D180.

INTERPRETATION:

vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development.

FUNDING:

Sanofi.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Lancet Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Lancet Infect Dis Assunto da revista: DOENCAS TRANSMISSIVEIS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos