Enhanced binding of antibodies to neutralization epitopes following thermal and chemical inactivation of human immunodeficiency virus type 1

Inactivation of viral particles is the basis for several vaccines currently in use. Initial attempts to use simian immunodeficiency virus to model a k illed human immunodeficiency virus type 1 (HIV-1) vaccine were unsuccessful , and limited subsequent effort has been directed toward a systematic study of the requirements For a protective killed HIV-1 vaccine. Recent insights into BTV-l virion and glycoprotein structure and neutralization epitopes l ed us to revisit whether inactivated HIV-1 particles could serve as the bas is for an HIV-I vaccine. Our results indicate that relatively simple proces ses involving thermal and chemical inactivation can inactivate HIV-1 by at least 7 logs. For some HIV-I strains, significant amounts of envelope glyco proteins are retained in high-molecular-weight fractions. Importantly, we d emonstrate retention of each of three conformation-dependent neutralization epitopes, Moreover, reactivity of monoclonal antibodies directed toward th ese epitopes is increased following treatment, suggesting greater exposure of the epitopes, In contrast, treatment of free envelope under the same con ditions leads only to decreased antibody recognition. These inactivated vir ions can also be presented by human dendritic cells to direct a cell-mediat ed immune response in vitro. These data indicate that a systematic study of HIV-1 inactivation, gp120 retention, and epitope reactivity with conformat ion-specific neutralizing antibodies can provide important insights for the development of an effective killed HIV-1 vaccine.