OUR PHILOSOPHY
We enter the clinic with immunogens for which we have convincing evidence that they behave according to design.
01.
bnAb-based HIV Vaccine
Development of a bnAb-based HIV vaccine is a complex task, but through our experimentation with various approaches to finding the optimal immunogen, we showed that it has the highest potential of being an effective HIV vaccine.
02.
Sequential Immunization Strategy
By employing advanced protein engineering tech, we generated novel immunogens and proved they have a high potential of eliciting bnAbs on key viral epitopes when administered as a part of a sequential multi-immunogen vaccination process.
03.
Iterative Human Phase I Trials to Improve Immunogen Design
The confirmation of vaccine candidates can only be accomplished through rigorous human clinical testing. We intend to use small-scale Phase I trials to rapidly test our vaccine concepts and then based on the results make iterative improvements to the design to better target bnAb sites. We will prioritize manufacturing and testing these candidates to eventually assemble immunization regimens targeting 2-3 bnAb sites. Knowledge gained from the development of one candidate will be applied to subsequent related candidate(s) to streamline development.
MAIN OBJECTIVE
Targeting Vulnerabilities on the Envelope Trimer
Env trimer is the target of bnAbs and the key focus point for all our vaccine designs. In our studies, we have determined the molecular structure of the Env, and we also defined 5 distinct sites on it. Sites that are particularly recognized by bnAbs, which makes them especially vulnerable to vaccines.
We work intensively to build upon our scientific advances to date, integrate them with our vaccine designs, and apply the lessons learned to clinical trials.
CHAVD Mindset
SEQUENTIAL VACCINATION
We designed distinct vaccination programs against each of the bnAb sites of vulnerability that are present on the HIV Envelope trimer.
Our studies have shown that the most likely final format for a successful bnAb-based HIV vaccine is one that induces bnAbs to at least 2 sites by sequential administration of 3 to 4 immunogens.
5
bnAb sites of vulnerability
90%+
targeted vaccine effectiveness
CORE STRATEGY
Iterative Immunogen Design
Although time-consuming and expensive, iteration is critical for success. The type of iterative immunogen design strategy we are pursuing revolves around immunogen testing that's followed by immunogen improvement and re-testing.
Rational Iterative Vaccine Design Approach.
Read MoreImmunogen design relies heavily upon the availability of bnAbs to identify epitope targets on HIV Env and the presence of bnAb precursors in people to prime, expand, and boost by immunization. A panel of virus sequences is essential to assess neutralization breadth and potency of bnAbs and to determine whether serum responses from immunization experiments are on target. Our investigators will focus on generating these key resources to propel HIV vaccine research in support of the Scripps CHAVD and the broader HIV vaccine field.
*Figure provided by the Burton Lab, The Scripps Research Institute.
KEY ELEMENTS
Basis of our Vaccine Discovery Process
- Inducing bnAbs to several sites on the HIV envelope trimer
- Creating distinct vaccine programs against each of the five bnAb sites
- Designing immunogens capable of eliciting antibodies that can prevent HIV acquisition
- Entering clinical trials only with immunogens which behave according to design
- Focusing our vaccine design strategy on continuous iteration
- Building on our scientific advances and integrating them with our vaccine designs
Electron Microscopy Polyclonal Epitope Mapping of Ab Responses to Vaccination.
A detailed understanding of immune response parameters is crucial to iterative vaccine design. Electron Microscopy Polyclonal Epitope Mapping (EMPEM) indicates the proportion of a given response that is directed to the desired region of HIV Env versus those which are off-target. The immunogen can then be modified to eliminate the off-target in favor of on-target responses. We have invested heavily in developing tools such as EM mapping of vaccine responses and are now refining these and other high-throughput tools for the analysis of Ab responses to monitor immune responses in clinical trials.
*Figure provided by Lars Hangartner, The Scripps Research Institute.