Principles for production of effective defined subunit vaccines. Deduction from a model experiment

Abstract

The spike glycoprotein of Semliki Forest Virus (SFV) were prepared in three physical forms: (1) 4.5 S complex, a complex of one spike and 75 molecules of Triton X-100; (2) the 29 S complex, a protein micelle of eight spikes virtually devoid of lipid and detergent (mol. wt 9.4 × 10 5) and (3) virosomes in which the spike proteins have been reconstituted into vesicles of egg lecithin. BALB/c mice were vaccinated with a single injection of either of these preparations and challenged 14 days later with different doses of a lethal strain of SFV. Most of the mice survived even the highest challenge dose when vaccinated with protein micelles or virosomes. The extent of protection measured by the difference between the LD 50 in controls and in groups vaccinated with a single dose of either of the multimer forms of vaccine was then higher than 10 3.7. Mice vaccinated with the monomer form of spike protein were only slightly protected. In conclusion, the spike proteins from membranes viruses can be prepared in defined physical forms with no detergent which are highly immunogenic.