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

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 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.

Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine

“…Figure 1 ). A ChAdOx1 vaccine encoding an irrelevant filovirus antigen (EBOV) was used as a negative control, 20 which showed a low level of binding to the anti-ChAdOx1 nCoV-19 vaccine serum (∼0.5–2% cells across all experiments). This observation accounts for antibodies raised against the vector itself rather that the vaccine antigen.…”

Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine

“…1 ). A ChAdOx1 vaccine encoding an irrelevant filovirus antigen (EBOV) was used as a negative control ( 20 ), which showed a low level of binding to the anti-ChAdOx1 nCoV-19 vaccine serum (~0.5–2% cells across all experiments). This observation accounts for antibodies raised against the vector itself rather that the vaccine antigen.…”

Vaccines based on the replication-deficient simian adenoviral vector ChAdOx1: Standardized template with key considerations for a risk/benefit assessment

“…Pre-clinical work which is expected to lead into clinical trials in the near future include ChAdOx1 vectored vaccines expressing Ebola (Bivalent), Crimean-Congo Hemorrhagic Fever, Nipah and Lassa antigens. See 4.11 [22] , [24] , [25] 5.2. What is the identity and source of the transgene?…”

“…Several pre-clinical studies have been performed using the ChAdOx1 vector including preliminary research of vaccine candidates for use in potential pandemic situations. Studies in small animal models have shown good potential of a number of ChAdOx1 vectored vaccines including those encoding antigens from influenza virus [19] , [20] , [21] , Nipah virus [22] , Zika virus [23] , Lassa virus [24] , filoviruses [25] , MERS-Cov virus [26] , SARS-CoV-2 virus [27] , [28] , [29] , blue tongue virus [30] , Rift Valley fever virus [31] , [32] , [33] , Chikungunya virus [34] , [35] , Human Immunodeficiency virus (HIV) [36] , [37] , Human papilloma virus (HPV) [38] , Hepatitis C virus [39] , [40] and Hepatitis B virus [41] . In some studies, large animals specific for the viral disease of concern were used, for example, pigs for ChAdOx1 expressing influenza virus haemagglutinin, sheep for the ChAdOx1 vector expressing blue tongue virus antigens, and sheep, cattle, dromedary camels and goats for ChAdOx1 expressing Rift Valley fever virus antigens.…”