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. Viral subunit vaccines contain epitopes that elicit non-neutralizing immune responses. Here, Du et al . mask an immunodominant non-neutralizing epitope on a MERS coronavirus subunit vaccine with a glycan probe, leading to significantly improved efficacy of the vaccine.
【초록키워드】 viruses, Efficacy, Vaccine, Vaccine design, variant, MERS-CoV, immune responses, Subunit vaccine, Neutralizing, epitope, MERS coronavirus, subunit, transgenic mice, life-threatening, host immune responses, immunodominant, probe, effective, evaluate, significantly, determine, elicit, the receptor-binding domain, the vaccine, Du et al, eliminated, non-neutralizing epitope, 【제목키워드】 Subunit vaccine, Neutralizing, MERS coronavirus,