Chimeric Trojan Protein Insertion in Lentiviral Membranes Makes Lentiviruses Susceptible to Neutralization by Anti-Tetanus Serum Antibodies.

Abstract

This study describes the initial testing of a novel strategy for neutralization of lentiviruses using the fundamental biology of enveloped viruses' assembly and budding. In the field of gene therapy, viral vector surface proteins have been manipulated in order to redirect host cell specificity by alteration of pseudo-types. This study tested whether known viral pseudo-typing proteins or surface proteins known to be recruited to the human immunodeficiency virus (HIV) envelope could be engineered to carry neutralizing epitopes from another microorganism onto the lentiviral surface. The results identify ICAM1 as a novel vehicle for lentiviral pseudo-typing. Importantly, the study shows that in a model lentiviral system, ICAM1 can be engineered in chimeric form to result in expression of a fragment of the tetanus toxoid on the viral membrane and that these viruses can then be neutralized by human serum antibodies protective against tetanus. This raises the possibility of delivering chimeric antigens as a gene therapy in HIV-infected patients.