Viral subunit vaccines often contain immunodominant non-neutralizing epitopes that divert host immune responses. These epitopes should be eliminated in vaccine design, but there is no reliable method for evaluating an epitope's capacity to elicit neutralizing immune responses. Here we introduce a new concept 'neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing immunogenicity. To determine the NII, we mask the epitope with a glycan probe and then assess the epitope's contribution to the vaccine's overall neutralizing immunogenicity. As proof-of-concept, we measure the NII for different epitopes on an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS-CoV). Further, we design a variant form of this vaccine by masking an epitope that has a negative NII score. This engineered vaccine demonstrates significantly enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge. Our study may guide the rational design of highly effective subunit vaccines to combat MERS-CoV and other life-threatening viruses.
Bibliographical noteFunding Information:
This work was supported by NIH grants R01AI089728 and R01AI110700 (F.L.), NIH grant PO1AI060699 (S.P.), NIH grants R01AI098775, U01AI124260, R21AI109094 and the intramural fund of New York Blood Center NYB000348 (L.D. and S.J.), NIH grant R21AI113206-01 and pilot grants from the Center for Biodefense and Emerging Infectious Diseases and from the Galveston National Laboratory (C.K.T), China National
© 2016 The Author(s).