Lessons learned from Zaire ebolavirus to help address urgent needs for vaccines against Sudan ebolavirus and Marburg virus

Figures & data

Table 1. Key gaps in Ebola vaccine development as of early 2014

Category	Gap	Status as of Early 2014
Clinical	Safety and Immunogenicity Data	Phase 1 data from Ad5- and DNA-vectored vaccines only.
	Dose Selection	No dose selection to move into further development.
	Immune Assays	ELISA, intracellular T cell staining, and ELISPOT used to assess immunology.
Non-Clinical	Efficacy in Nonhuman Primates	Proof of concept efficacy available for VRP, VLP, Adenovirus, VSV, DNA.
	GLP Toxicology	GLP toxicology lacking for these leads.
	Concurrence on Animal Species, Route of Challenge, and Challenge Strains	No FDA concurrence on animal species, route of challenge, or challenge strains.
Chemistry, Manufacturing, and Controls	Lot Release Assays	Limited number of assays available.
	Small Scale Process Development	Processes available for rVSV∆G-EBOV; Lab scale processes developed for other leads.
	cGMP Manufactured Lots	cGMP lot of rVSV∆G-EBOV; No other cGMP lots ready for clinical evaluation.
	Stability Data to Support Clinical Studies	Limited understanding of stability profiles.

*VRP = Viral Replicon, VLP = Virus-Like Particle, VSV = Vesicular Stomatitis Virus, GLP = Good Laboratory Practices, cGMP = current Good Manufacturing Practices.

Table 2. Current State of SUDV and MARV gaps as of the end of 2019

Category	Gap	Current Status SUDV	Current Status MARV
Clinical	Safety and Immunogenicity Data	Phase 1 data from ChAd3, Ad5, DNA constructs. Phase 1 underway for multivalent Ad26/MVA.	Phase 1 data from DNA construct. Phase 1 underway for ChAd3 and multivalent Ad26/MVA.
	Dose Selection	No dose selection for further studies.	No dose selection for further studies.
	Immune Assays	Qualified immune assays needed.	Qualified immune assays needed.
Non-Clinical	Efficacy in Nonhuman Primates	Proof of concept available for VSV, VRP, VLP, Ad5, DNA, ChAd3.	Proof of concept available for VSV, VLP, DNA, Ad5, ChAd3.
	GLP Toxicology	GLP toxicology for ChAd3 and multivalent Ad26/MVA.	GLP toxicology for ChAd3 and multivalent Ad26/MVA.
	Concurrence on Animal Species, Route of Challenge, and Challenge Strains	No official concurrence on animal species, virus strain, or route of challenge.	No official concurrence on animal species, virus strain, or route of challenge.
Chemistry, Manufacturing, and Controls	Lot Release Assays	Development, qualification, and validation required for key non-compendial assays.	Development, qualification, and validation required for key non-compendial assays.
	Small Scale Process Development	Lab-scale development for ChAd3, DNA, and Ad26/MVA vectors.	Lab-scale development for ChAd3, DNA, and Ad26/MVA vectors.
	GMP Manufactured Lots	GMP lots available for ChAd3 and Ad26/MVA. Additional material needed for all candidates.	GMP lots available for ChAd3 and Ad26/MVA. Additional material needed for all candidates.
	Stability Data to Support Clinical Studies	Limited understanding of stability profiles.	Limited understanding of stability profiles.

*VRP = Viral Replicon, VLP = Virus-Like Particle, VSV = Vesicular Stomatitis Virus, GLP = Good Laboratory Practices, cGMP = current Good Manufacturing Practices, Ad5 = Adenovirus serotype 5, Ad26 = Adenovirus serotype 26, ChAd3 = Chimpanzee Adenovirus serotype 3, MVA = Modified Vaccinia Ankara.