Cross-Protective Multivalent Vaccine for Tick-Borne Flaviviruses

DESCRIPTION provided by applicant The tick borne flavivirus TBFV group includes a number of important human pathogens that result in serious encephalitic or hemorrhagic diseases that are either Category B or C priority pathogens The TBFV are considered to be emerging or re emerging pathogens due to increases in the number of human cases the expansion of geographic distribution and emergence of new viruses This application is directed at the development of a multivalent TBFV vaccine that provides broad cross protection against at least five viruses in this group Central European subtype of tick borne encephalitis TBE TBEV Eu Far Eastern subtype TBE FE Alkhurma hemorrhagic fever virus AHFV Kyasanur Forest disease virus KFDV and Omsk hemorrhagic fever virus OHFV Inactivated vaccines exist for TBEV Eu TBE FE and KFD in some endemic countries but there are no vaccines for AHFV and OHFV The development of monotypic vaccines against individual pathogens provides a strategy to mitigate the threat posed on a regional basis however the number of different viruses in the TBFV group poses a challenge in providing protection against all of the viruses in the group Furthermore there is no registered TBFV vaccine in the U S The lack of a vaccine in the U S has been deemed an unmet need by NIAID An approach to provide broad protection against the TBFV group is the development of a multivalent vaccine that provides cross protection against most if not all of the TBFVs This vaccine will be developed by evaluating various combinations of soluble recombinant subunits proteins representing the envelope E protein from these five TBFVs Preliminary data with recombinant TBEV Eu has established a proof of principle for the potential of this approach The monovalent rTBEV EU vaccine has been demonstrated to provide monotypic and partial cross protection and will serve as the core on which the multivalent vaccine will be established The Specific Aims of this project are development and evaluation of the immunogenicity and cross reactive potential cross virus neutralizing ability of additional E subunit proteins for inclusio in the multivalent vaccine assess the cross protective potential of selected combinations of recombinant TBFV E proteins in a mouse challenge model and assess the potency of the selected multivalent vaccine to support further development of the vaccine To accomplish these goals an established stable insect expression system with demonstrated FDA regulatory experience will be utilized to produce the recombinant E proteins This includes the use of a modern adjuvant that has potential for advancement to human clinical trials The selection of the multivalent candidate vaccine will focus on a vaccine composition with the least number of components E proteins that provides the greatest level of cross protection To accomplish the objectives of the proposed research a strong multidisciplinary team of scientists has been assembled that provides the means to develop and evaluate a successful multivalent TBFV cross protective vaccine The development of multivalent TBFV vaccine would be of great value and in line with the priorities of NIH NIAID to develop multivalent and cross protective vaccine technologies PUBLIC HEALTH RELEVANCE The proposed research is focused on developing a candidate vaccine that protects against a family of related viruses in the tick borne flavivirus TBFV group
which causes disease in humans The vaccine candidate would be a single multivalent vaccine that would provide protection against many viruses in the TBFV group The approach is based on a technology to produce vaccine components comprised of recombinant subunit envelope proteins Although TBFVs are normally found outside the U S they are identified as priority pathogens so a multivalent vaccine would help meet the mission of providing protection for U S citizens against several priority pathogens biothreat agents with a single vaccine Such a multivalent TBFV vaccine can be utilized to protect military and state department personnel first responders and U S TBFV virus researchers who are currently forced to go abroad for vaccination in addition to travelers or people at risk in endemic areas