Plant-made vaccines and reagents for the One Health initiative

Rybicki, Edward Peter

Dengue viruses (DENV) are a problematic vaccine target, given that antibodies directed against any one of the 4 dengue subtypes will not protect against infection by any of the others, and may in fact result in ADE of infection by them, which can result in dengue hemorrhagic fever. While there is now a licensed quadrivalent live vaccine, 43 new concerns over the interaction of dengue and other flaviviruses and in particular Zika virus, and the possibility of reciprocal ADE between them, have prompted caution over its use. For this reason, subunit vaccines consisting of E protein DIIIsimilar to the WNV example above, and which are serotype-specific and elicit neutralising antibodies which are not involved in ADEhave been trialled in monkeys, with good efficacy shown: 44 however, as with any other protein vaccine, production will probably be expensive. A group based in Korea has accordingly explored a variety of options of producing DIII-derived vaccines in plants, including fusion of a DIII with cholera toxin B subunit (CTB) and production in transgenic tobacco; 45 fusing a consensus DIII, which elicits neutralising antibodies against all 4 dengue virus serotypes, to M cell-targeting peptide ligand (Co1), producing it in transgenic rice calli and showing it was targeted to the mucosal immune system in mice; 46 and modifying the recombinant immune complexes (RIC) shown to work for Zaire ebolavirus GP1 by fusing the Ebola GP1 epitope binding the 6D8 mAb to the dengue virus consensus DIII domain, and then to the mAb, and producing it transiently in tobacco. 47 The purified hybrid dengue-Ebola RIC (DERIC) bound C1q, and elicited potent virus-neutralising Abs in mice without the use of adjuvants. Another group used transplastomic tobacco to produce the 4 serotype DIII proteins to moderate yield, without testing their immunogenicity. 48 This work shows that it is possible to produce candidate dengue subunit vaccines in plants that are at least the equivalent of conventionally-produced candidates.