USE OF DNAS EXPRESSING HIV-1 ENV AND NONINFECTIOUS HIV-1 PARTICLES TORAISE ANTIBODY-RESPONSES IN MICE

Two DNA constructs encoding portions of the human immunodeficiency vir us type-1 (HIV-1) genome have been used to raise antibody responses in BABL/c mice. One DNA (pNL4-3.env) expresses the natural form of the e nvelope glycoprotein (Env) of HIV-1-NL4-3 (NL4-3). The second (pNL4-3. dpol) produces noninfectious NL4-3 particles. These two DNAs (alone or in combination) raised only transient titers of anti-Env IgG. In the same group in which pNL4-3.dpol DNA raised only transient antibody res ponses to Env, this DNA raised persistent antibody responses to the p2 4 virion capsid protein (CA). Antibody responses to Env and CA also sh owed different abilities to be boosted. The final boosts of pNL4-3.dpo l DNA increased titers of anti-CA antibody, but failed to boost the fa iling titers of anti-Env antibody. At peak titers of anti-Env activity , sera with relatively low ELISA liters of anti-Env IgG (end points of 1:6250) had good liters of neutralizing antibody (similar to 1:3800 f or 50 TCID50 of NL4-3). At the end of the experiment (a time when anti -Env antibodies had fallen to near background levels), in vitro-restim ulated splenocytes from both pNL4-3.env and pNL4-3.dpol DNA vaccine gr oups exhibited similar cytotoxic activity. (C) 1995 Academic Press, In c.