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 responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have previously reported that DNA-primed anti-Env antibody responses can be augmented by boosting with Env-expressing recombinant vaccinia viruses. We report here that recombinant Env protein provides a more effective boost of DNA-initiated antibody responses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of anti-Env responses. While titers increased rapidly after boosting, avidity and neutralizing activity matured more slowly over a 6-month period following protein boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapted, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which expressed noninfectious virus-like particles. In contrast to immunizations with HIV-1 Env, DNA immunizations with the influenza virus hemagglutinin glycoprotein did not require a protein boost to achieve high-titer antibody with good avidity and persistence.