The envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the non-structural (NS) and capsid (C) antigens which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses amongst different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses, and might thus impair vaccine performance.
Grifoni A, Voic H, Dhanda SK, Kidd CK, Brien JD, Buus S, Stryhn A, Durbin AP, Whitehead S, Diehl SA, De Silva AD, Balmaseda A, Harris E, Weiskopf D, Sette A. (2020). T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species. Journal of virology