Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in late 2019 causing CoronavirusDisease 2019 (COVID-19) and within months became a worldwide pandemic - as of the writing of this proposal,at least 82.5M people have been infected and more than 1.8M have died in addition to having a significant impacton the worldwide economy. Multiple vaccines are in development for COVID-19 and two of these have beenawarded emergency use approval from the US FDA based on RNA platforms. With our partners at HDT BioCorp. we are soon to enter phase I clinical trials with an RNA-based vaccine, HDT-301. While the developmentand deployment of these vaccines is exciting and has moved with unprecedented speed, it is unclear how durablethe immune responses will be and whether or not they will induce broad protection against emerging strains.Therefore, the ability to boost these vaccines should be investigated to determine if a prime / boost regimen canbe deployed in the face of waning immunity or newly emerging viral variants like the recently identified UK strain.As next generation candidates we are now producing 4 different adjuvants containing a non-GLA based TLR4active ingredient derived from MPL referred to as 3D(6acyl)-PHAD ("3D-PHAD"). These adjuvants are calledAlT4â¢, EmT4â¢, LiT4â¢, and MiT4. In this proposal, we will test each of these adjuvants in combination withrecombinant Covid-19 spike protein in mice as adjuvanted protein vaccines and as RNA vaccine boosters.Following immunization with protein / adjuvant, potential protection against multiple Covid-19 spike proteinvariants will be confirmed using both ELISA and viral neutralization assays. Lead combinations will then betested using a prime-boost strategy using a proprietary mRNA prime vaccination with HDT-301 followed by aadjuvanted protein boost. Specifically, we propose to (1) Down-select a lead adjuvant in mice and (2) Determineprotection from Covid-19 using an RNA prime protein boost immunization strategy. When this research iscompleted, we will have protocols and data supporting the use of these vaccines in further studies in higheranimal models leading to human trials as the data warrant.
Public Health Relevance Statement: PROJECT NARRATIVE
The severe acute respiratory syndrome coronavirus disease (COVID-19) has become a worldwide pandemic.
By determining protection from Covid-19 using an RNA prime protein boost immunization strategy and
developing a next generation protective vaccine we will have an impact on global health.
Project Terms:
