Catalytic antibodies and their applications.

Catalytic antibodies (CAbs) occur naturally in healthy individuals where they may form part of the innate immune system, but are preferentially found in those with autoimmune disease. CAbs can also be artificially engineered or elicited by immunizations. Their mechanisms of action include nucleophilic catalysis, induction of conformational strain, coordination with metal ions, and stabilization of transition states. Recent applications of CAbs with clinical significance include the conversion of cocaine to a non-psychoactive form, the degradation of nicotine, activation of prodrugs for targeted chemotherapy, protection from ultraviolet radiation, inhibition of HIV infectivity, and the destruction of aggregates of beta-amyloid implicated in Alzheimer's disease. Artificial CAbs are likely to find increasing applications in research, clinical medicine, diagnostics and manufacturing.

Generating neutralizing antibodies, Th1 response and MHC non restricted immunogenicity of HIV-I env and gag peptides in liposomes and ISCOMs with in-built adjuvanticity.

For enhancing immunogenicity and develop vaccine strategies using peptide based constructs against HIV-1, a chimeric peptide containing V3 loop and transmembrane sequence of gp41 with two glycine motifs as spacer was constructed. The V3-gp41, gp41 peptide and p17 and p24 peptides separately or in a cocktail were entrapped with or without MA729 as an immunoadjuvant in liposomes or ISCOMs. The immunogenicity, antigen induced T-cell proliferation and cytokine profiles of various formulations were studied in four different inbred strains of mice of H-2d, H-2b, H-2k and H-2q haplotypes, keeping alum as a control adjuvant. Both liposomes and ISCOM preparations elicited high titer and long lasting antibody response (60 days and above). When compared to the alum formulation, the liposomes co-entrapped with MA729 produced high antibody levels, comparable with that induced by ISCOMs. Peptide in alum, liposomes and ISCOMs enhanced both antigen specific IgG2a and IgG2b isotypes and high T-cell stimulation index. Peptide formulations also induced antibodies with high affinity and in vitro neutralizated the formation of HIV-1 syncytia. T-cell supernatants contained high levels of IFN-gamma and IL-2. Thus formulation in these adjuvants induced a predominant Th1 like response with MA729 as a versatile novel delivery vehicle for stimulating the appropriate arm of the immune response that can selectively modulate MHC class I or MHC class II response. The above peptide can be of wide vaccination interest as a means to improve immune responses to several other HIV-1 antigens and may serve as candidates for vaccine development.