Developing vaccines against filoviruses, such as Ebola and Marburg, presents significant challenges due to their complex pathogenesis and immune evasion mechanisms. Filoviruses exhibit high genetic variability, which complicates the identification of universally effective antigens. Furthermore, these viruses can rapidly mutate, potentially rendering vaccines ineffective.
A phase I study involving 230 participants and testing a recombinant protein adjuvanted with ISCOMatrix type of saponin formulation evaluated the immunogenicity and safety of the vaccine against Ebola (Fries, et al., 2020).
In an infection study in mice (Lövgren Bengtsson, et al., 2016), a recombinant protein of Ebola Zaire strain adjuvanted with ISCOMatrix induced high levels of antibodies, IgG specific, significantly superior to the antigen alone and to aluminum phosphate adjuvanted vaccine. The survival rate after infection attained 100%. The adjuvanted vaccine enhanced both CD4+ and CD8+ T cells, IFN-secreting cells remained significantly high 60 days after immunization. The regular saponin adjuvant rate of 5 µg showed partially better efficacy than 2.5 µg.
Another and recent infectious exploratory study of a protein-polymer adjuvant system incorporating QS-21, showed an increase in the immunogenicity of the subunit Ebola vaccine and favorable safety in mice.
The antibody titer was higher for the QS-21 adjuvanted vaccine, compared to squalene based o/w emulsion (Addavax). The authors infer that QS-21 induced the activation of NLRP3 inflammasome, responsible for the activation and death of subcapsular sinus macrophages that in return triggers the recruitment of immune cells to assemble innate and adaptive immunity (Wang, et al., 2024).
References
1. Fries, L. et al., 2020. Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults. The Journal of Infectious Diseases, 222(4), pp. 572-582.
2. Lövgren Bengtsson, K. et al., 2016. Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice. Vaccine, Volume 34, pp. 1927-1935.
3. Wang, C. et al., 2024. A broadly applicable protein-polymer adjuvant system for antiviral vaccines. EMBO Molecular Medecine.
