Project Abstract - A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema
pallidum
The scientific premise of this CRC proposal rests upon our three decades of work defining the molecular
architecture of the outer membrane (OM) of Treponema pallidum subsp. pallidum (TPA), coupled with our
successes combining bioinformatics, biophysical techniques, and localization methods with live TPA to
topologically characterize TPA outer membrane proteins (OMPs) and define the syphilis spirochete’s
‘OMPeome’--its repertoire of OMPs. The central hypothesis is that the principal targets for a syphilis vaccine
reside within TPA’s repertoire of rare OMPs.
The current application builds upon the work of the current CRC U19 grant awarded to the two mPIs of this
proposal (Moody and Radolf). This proposal brings together the expertise in spirochetology (Univ. of
Connecticut) and vaccine development (Duke Human Vaccine Institute) to develop vaccines targeting TPA
OMPs. The overarching hypothesis is that vaccines targeting TPA OMPs will elicit antibodies that can
recognize intact treponemes, provide protection in animal models, and be producible using Good
Manufacturing Practices (GMP) at the scale needed to perform a phase 1 clinical trial.
This CRC proposal will focus on two main aims: Aim 1) Selection of an ECL vaccinogen panel and production
of ECL mAbs with functional activity, with subaim 1.1 of finalizing the ECL vaccinogen panel through robust
preclinical animal studies (Univ. of Connecticut) and subaim 1.2 of producing ECL mAbs with functional activity
(Duke Human Vaccine Institute), and Aim 2) Selection and optimization of an ECL vaccine platform, with
subaim 2.1 of generating functional ECL-specific Abs using mRNA-LNP immunogens (Univ. of Pennsylvania),
and subaim 2.2 of generating functional ECL-specific Abs using SpyVLPs (Univ. of Connecticut), to be
compared in animal protection studies in subaim2.3.
Successful completion of the aims of this CRC U01 proposal will provide the preclinical data needed for an IND
submission to the FDA, complete the process development for GMP production, and will result in the full
design of a GMP campaign strategy and a plan for toxicology testing.