A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector

Vaccines

KuanM. Cha¹  Sarah Sebastian¹  Marta Ulaszewska¹  Teresa Lambe¹  Sarah Gilbert¹  Amy Flaxman¹  Ciaran Gilbride¹  AlexandraJ. Spencer¹  Hannah Sharpe¹  Roger Hewson²  Stuart Dowall²  Edward Wright³ 

[1]Nuffield Department of Medicine, Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK

[2]Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK

[3]School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK

关键词: Ebola;    Marburg;    filovirus;    vaccine;    viral vector;   

DOI  :  10.3390/vaccines8020241

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown