Arthur Friedman

Preclinical efficacy of a prototype DNA vaccine: Enhanced protection against antigenic drift in influenza virus

Vaccination with plasmid DNA expression vectors encoding foreign proteins elicits antibodies and cell-mediated immunity and protects against disease in animal models. We report a comparison of DNA vaccines, using contemporary human strains of virus, and clinically licensed (inactivated virus or subvirion) vaccines in preclinical animal models, to better predict their efficacy in humans. Influenza DNA vaccines elicited antibodies in both non-human primates and ferrets and protected ferrets against challenge with an antigenically distinct epidemic human influenza virus more effectively than the contemporary clinically licensed vaccine. These studies demonstrate that DNA vaccines may be more effective, particularly against different strains of virus, than inactivated virus or subvirion vaccines.

A gastrin-releasing peptide antagonist containing a ψ(CH2O) amide bond surrogate

The [Leu26-psi(CH2O)Leu27] derivative of N-Ac-GRP20-27-peptide amide was prepared and evaluated as a gastrin-releasing peptide antagonist. This psi(CH2O) derivative was found to be a more potent inhibitor of [3H-Phe15]GRP15-24NH2 binding and N-Ac-GRP20-27NH2 induced mitogenesis in Swiss 3T3 fibroblasts than the related nitrogen analog [Leu13-psi(CH2NH)Leu14] bombesin. Possible reasons for the improved activity of the (CH2O) insert relative to the (CH2NH) group include increased hydrophobicity and a reduced tendency of the oxygen derivative to form hydrogen bonds.

DNA Vaccines for Bacteria and Viruses

DNA vaccines are nonreplicating plasmids encoding genes from pathogens. The antigenic proteins are thus expressed in the cells of the vaccinated host and result in the generation of both antibody and cell-mediated immune responses. The ability to generate proteins with native conformation contrasts with certain recombinant protein or inactivated viral vaccines, and offers the means to generate antibodies against the relevant epitopes. Because the desired proteins are synthesized within the host, cell-mediated immune responses can be generated, without the inherent risks of certain viral vectors or of attenuation of certain attenuated viruses (e.g., HIV) and bacteria.