STUDIES OF THE NEUTRALIZING ACTIVITY AND AVIDITY OF ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENV ANTIBODY ELICITED BY DNA PRIMING AND PROTEIN BOOSTING

DNA vaccination is an effective means of eliciting strong antibody res ponses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing ant ibody responses to human immunodeficiency virus type 1 (HIV-1) envelop e glycoprotein (Env). We have previously reported that DNA-primed anti -Env antibody responses can be augmented by boosting with Env-expressi ng recombinant vaccinia viruses. We report here that recombinant Env p rotein provides a more effective boost of DNA-initiated antibody respo nses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of a nti-Env responses. While titers increased rapidly after boosting, avid ity and neutralizing activity matured more slowly over a 6-month perio d following protein boosting. DNA priming and protein immunization wit h HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapt ed, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which exp ressed noninfectious virus-like particles. In contrast to immunization s with HIV-1 Env, DNA immunizations with the influenza virus hemagglut inin glycoprotein did not require a protein boost to achieve high-tite r antibody with good avidity and persistence.