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Monoclonal antibody 2F10 is an "internalimage" anti-idiotype (anti-id) antibody capable of micking the group-specific "a" determinant of human hepatitis B surface antigen (HBsAg). By mRNA sequencing and computer-assisted molecular modeling of monoclonal antibody 2F10, we identified a 15-amino acid region of the heavy-chain hypervariable region that has partial residue homology with sequences of the "a" determinant epitopes of HsAg. We have established that a linear 15-mer peptide from a contiguous region on the anti-id antibody can (i) generate anti-HBsAg-specific antibodies when injected into mice, (ii) prime murine lymph node cells for in vitro HBsAg-speciflc T-ceff prolerative responses, and (ii) stimulate in vitro human CD4+ T cells that were primed in vivo to HBsAg by natural infection with hepatitis B virus or v itio with a commercially available lBsAg vaccine. Siflcant y, this peptide could also stimulate CD4+ T cells of human hepatitis B virus carriers. We conclude that a 15-mer peptide derived frot the anti-id sequence can duplicate the B-and T-cell stimulatory activity of the intact anti-id antibody and the antigen that is mimicked, HBsAg.Infection with human hepatitis B virus (HBV) results in a gamut of clinical symptoms ranging from minor flu-like symptoms to death. The wide spectrum of responses is believed to be accounted for by the host's immune response to the virus because HBV is not directly cytopathic for hepatocytes (1). The specific serologic marker of HBV infection is the envelope protein, hepatitis B surface antigen (HBsAg), which contains three related proteins designated S, M (S plus pre-52), and L (M plus pre-Sl). All ofthese proteins share the 226-amino acid sequence of the S protein (in this paper, HBsAg will refer to the S protein). HBsAg possesses a common group-specific a determinant and two sets of mutually exclusive subtype-specific determinants d/y and w/r. Because antibodies directed toward the a determinant confer protection against HBV infection, regardless of subtype (2), any vaccine developed to prevent HBV infection should elicit immunity to the a determinant.The immune network theory proposed by Jerne (3) predicts the appearance of several types of anti-idiotype (anti-id) antibodies during the immune response to a given antigen. The subset of "internal-image" anti-id antibodies (termed Ab2f3) has been proposed to be anti-paratopic and to mimic the molecular features of the original antigen (4, 5). This working hypothesis is based on the concept that certain homologous or analogous molecular motifs of the anti-id sequence can mimic specific immunogenic epitopes of the infectious organism, thereby inducing a protective immune response (4, 5). Such anti-id antibodies have been used in various experimental systems as surrogate vaccines against specific bacterial, viral, and parasitic organisms (for review, see refs. 6 and 7).We produced six monoclonal anti-id antibodies against a monoclonal antibody (mAb), designated H3F5 (id) (8), which recognizes the protective a de...

We present Yogi, a tool that checks properties of C programs by combining static analysis and testing. Yogi implements the Dash algorithm which performs verification by combining directed testing and abstraction. We have engineered Yogi in such a way that it plugs into Microsoft's Static Driver Verifier framework. We have used this framework to run Yogi on 69 Windows Vista drivers with 85 properties. We find that the new algorithm enables Yogi to scale much better than Slam, which is the current engine driving Microsoft's Static Driver Verifier.

Abstract. This paper addresses the problem of automatically generating quantified invariants for programs that manipulate singly and doubly linked-list data structures. Our algorithm is property-directed-i.e., its choices are driven by the properties to be proven. The algorithm is able to establish that a correct program has no memory-safety violations-e.g., null-pointer dereferences, double frees-and that data-structure invariants are preserved. For programs with errors, the algorithm produces concrete counterexamples.More broadly, the paper describes how to integrate IC3 with full predicate abstraction. The analysis method is complete in the following sense: if an inductive invariant that proves that the program satisfies a given property is expressible as a Boolean combination of a given set of predicates, then the analysis will find such an invariant. To the best of our knowledge, this method represents the first shapeanalysis algorithm that is capable of (i) reporting concrete counterexamples, or alternatively (ii) establishing that the predicates in use are not capable of proving the property in question.