Whitehead, Stephen (NIAID)
Woodson, Sara (NIAID)
Durbin, Anna (Johns Hopkins University)
Pletnev, Alexander (NIAID)
Tsetsarkin, Konstantin (NIAID)
This application claims live attenuated Zika viruses and vaccines, attenuated chimeric Zika viruses and vaccines, and multivalent immunogenic compositions comprising Zika vaccines and vaccines for other flaviviruses. The chimeric Zika viruses claimed include a first nucleotide sequence encoding at least one structural protein from a Zika virus (ZIKV), a second nucleotide sequence encoding at least one nonstructural protein from a first flavivirus, and a third nucleotide sequence of a 3' untranslated region from a second flavivirus. The multivalent immunogenic compositions claimed comprise an attenuated ZIKV vaccine or an attenuated chimeric ZIKV vaccine (or their combination) together with one or more of a first attenuated virus that is immunogenic against dengue serotype 1, a second attenuated virus that is immunogenic against dengue serotype 2, a third attenuated virus that is immunogenic against dengue serotype 3, and a fourth attenuated virus that is immunogenic against dengue serotype 4. The present disclosure also claims methods of inducing immune responses, as well as preventing ZIKV and another flavivirus, e.g., dengue virus.
Such a chimeric vaccine candidate may induce a humoral (antibody) and T-cell response to ZIKV, while the nonstructural proteins of dengue virus will likely induce a T-cell response. The dengue platform also contains a deletion in the TL2 stem-loop structure of the 3' untranslated region (UTR), called Delta30 and Delta30/31 attenuating mutations. The Delta30 deletion has proven to be one of the defining characteristics of the successful one dose dengue vaccine, which is currently in a large scale (17,000 patient) clinical trial in Brazil.
- One-dose vaccine
- Ease of manufacture
- Can be included in multivalent flavivirus vaccines