The immune space: a concept and template for rationalizing vaccine development.

Abstract Empirical testing of candidate vaccines has led to the successful development of a number of lifesaving vaccines. The advent of new tools to manipulate antigens and new methods and vectors for vaccine delivery has led to a veritable explosion of potential vaccine designs. As a result, selection of candidate vaccines suitable for large-scale efficacy testing has become more challenging. This is especially true for diseases such as dengue, HIV, and tuberculosis where there is no validated animal model or correlate of immune protection. Establishing guidelines for the selection of vaccine candidates for advanced testing has become a necessity. A number of factors could be considered in making these decisions, including, for example, safety in animal and human studies, immune profile, protection in animal studies, production processes with product quality and stability, availability of resources, and estimated cost of goods. The "immune space template" proposed here provides a standardized approach by which the quality, level, and durability of immune responses elicited in early human trials by a candidate vaccine can be described. The immune response profile will demonstrate if and how the candidate is unique relative to other candidates, especially those that have preceded it into efficacy testing and, thus, what new information concerning potential immune correlates could be learned from an efficacy trial. A thorough characterization of immune responses should also provide insight into a developer's rationale for the vaccine's proposed mechanism of action. HIV vaccine researchers plan to include this general approach in up-selecting candidates for the next large efficacy trial. This "immune space" approach may also be applicable to other vaccine development endeavors where correlates of vaccine-induced immune protection remain unknown

Verification as Learning Geometric Concepts

Abstract. We formalize the problem of program verification as a learning problem, showing that invariants in program verification can be regarded as geometric concepts in machine learning. Safety properties define bad states: states a program should not reach. Program verification explains why a program’s set of reachable states is disjoint from the set of bad states. In Hoare Logic, these explanations are predicates that form inductive assertions. Using samples for reachable and bad states and by applying well known machine learning algorithms for classification, we are able to generate inductive assertions. By relaxing the search for an exact proof to classifiers, we obtain complexity theoretic improvements. Further, we extend the learning algorithm to obtain a sound procedure that can generate proofs containing invariants that are arbitrary boolean combinations of polynomial inequalities. We have evaluated our approach on a number of challenging benchmarks and the results are promising