Core D: Early and IND-Enabling Translational Research for Vaccines and MAbs

ABSTRACT/PROJECT SUMMARY – Core D (Early and IND-Enabling Translational Research for Vaccines and mAbs) Core D will leverage the relationship between vaccines and antibodies to optimize the translational activities performed by the PABVAX Center. Vaccines and antibodies are inextricably linked: 1. mAbs can help define protective epitopes for a vaccine

2. mAbs can help establish correlates of protection for vaccines 3. Vaccine antigens can be used to discover mAbs 4. mAbs can provide an alternative to a vaccine in immunocompromised populations and in emergency situations where immediate protection is required (i.e. there isn’t sufficient time to allow natural host

immunity to develop from vaccination) Developing mAb countermeasures and vaccines simultaneously will allow us to take advantage of natural synergies between the two types of interventions and more efficiently advance superior prototypes. To meet the goals of the PABVAX Center, Core D has the following Specific Aims:

Aim 1: Manufacture vaccine antigens and mAbs in support of the RPs and Cores Manufacturing will be performed by Mapp Biopharmaceutical and Genovac to support the efforts of the other Scientific Cores and the Research Projects. The largest scale manufacturing runs will be sufficient to support stability testing and NHP dosing. This will also include production of a mAb prototype for an intramuscular (IM)

long-acting alternative to a vaccine to be evaluated in Core E (Animal Models). Aim 2: Stability, manufacturability testing, and early process development of subunit vaccines. Small scale manufacturing, stability testing and early-stage process development will be performed. As vaccines are regulated by CBER, all activities will be performed consistent with regulatory expectations for this branch of

the FDA. Input from the Core’s vaccine industrial partners (Emergent Biosolutions and Moderna) will be integrated into the translational development efforts. Aim 3: Identification of correlates of protection, lead optimization, stability and manufacturability testing of mAbs. Together with Dr. Gunn, engineered mAbs (altered N-glycans, Fc mutations for effector functions and extended

half-life, multimeric formats and nanobodies from RP5) will be evaluated to correlate mechanisms of action with maximal efficacy. This work, in conjunction with stability and manufacturability assessment, will identify a lead prototype format to transition to early process development. The goal will be to identify a single prototype for

long-term intramuscular prophylaxis as well as for intravenous post-exposure prophylaxis and therapy. As mAbs are regulated by CDER, performance of all activities will be as per regulatory expectations.