A simian-adenovirus-vectored rabies vaccine suitable for thermostabilisation and clinical development for low-cost single-dose pre-exposure prophylaxis.

Détails

Ressource 1Télécharger: journal.pntd.0006870.pdf (1245.60 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_F6FC349F77D0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A simian-adenovirus-vectored rabies vaccine suitable for thermostabilisation and clinical development for low-cost single-dose pre-exposure prophylaxis.
Périodique
PLoS Neglected Tropical Diseases
Auteur(s)
Wang C., Dulal P., Zhou X., Xiang Z., Goharriz H., Banyard A., Green N., Brunner L., Ventura R., Collin N., Draper S.J., Hill AVS, Ashfield R., Fooks A.R., Ertl H.C., Douglas A.D.
ISSN
1935-2735 (Electronic)
ISSN-L
1935-2727
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
12
Numéro
10
Pages
e0006870
Langue
anglais
Résumé
Estimates of current global rabies mortality range from 26,000 to 59,000 deaths per annum. Although pre-exposure prophylaxis using inactivated rabies virus vaccines (IRVs) is effective, it requires two to three doses and is regarded as being too expensive and impractical for inclusion in routine childhood immunization programmes.
Here we report the development of a simian-adenovirus-vectored rabies vaccine intended to enable cost-effective population-wide pre-exposure prophylaxis against rabies. ChAdOx2 RabG uses the chimpanzee adenovirus serotype 68 (AdC68) backbone previously shown to achieve pre-exposure protection against rabies in non-human primates. ChAdOx2 differs from AdC68 in that it contains the human adenovirus serotype 5 (AdHu5) E4 orf6/7 region in place of the AdC68 equivalents, enhancing ease of manufacturing in cell lines which provide AdHu5 E1 proteins in trans. We show that immunogenicity of ChAdOx2 RabG in mice is comparable to that of AdC68 RabG and other adenovirus serotypes expressing rabies virus glycoprotein. High titers of rabies virus neutralizing antibody (VNA) are elicited after a single dose. The relationship between levels of VNA activity and rabies virus glycoprotein monomer-binding antibody differs after immunization with adenovirus-vectored vaccines and IRV vaccines, suggesting routes to further enhancement of the efficacy of the adenovirus-vectored candidates. We also demonstrate that ChAdOx2 RabG can be thermostabilised using a low-cost method suitable for clinical bio-manufacture and ambient-temperature distribution in tropical climates. Finally, we show that a dose-sparing effect can be achieved by formulating ChAdOx2 RabG with a simple chemical adjuvant. This approach could lower the cost of ChAdOx2 RabG and other adenovirus-vectored vaccines.
ChAdOx2 RabG may prove to be a useful tool to reduce the human rabies death toll. We have secured funding for Good Manufacturing Practice- compliant bio-manufacture and Phase I clinical trial of this candidate.
Mots-clé
Adenoviruses, Simian/genetics, Adjuvants, Immunologic/administration & dosage, Animals, Antibodies, Neutralizing/blood, Antibodies, Viral/blood, Costs and Cost Analysis, Drug Carriers, Drug Stability, Female, Genetic Vectors, Immunization Schedule, Mice, Pre-Exposure Prophylaxis/methods, Rabies/prevention & control, Rabies Vaccines/administration & dosage, Rabies Vaccines/economics, Rabies Vaccines/genetics, Rabies Vaccines/immunology, Vaccines, Synthetic/administration & dosage, Vaccines, Synthetic/economics, Vaccines, Synthetic/genetics, Vaccines, Synthetic/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/11/2018 16:27
Dernière modification de la notice
20/08/2019 17:23
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