Comparison of immunity generated by nucleic acid-, MF59-, and ISCOM-formulated human immunodeficiency virus type 1 vaccines in rhesus macaques: Evidence for viral clearance

The kinetics of T-helper immune responses generated in 16 mature outbred rh esus monkeys (Macaca mulatta) within a 10-month period by three different h uman immunodeficiency virus type 1 (HIV-1) vaccine strategies were compared . Immune responses to monomeric recombinant gp120(SF2) (rgp120) when the pr otein was expressed in vivo by DNA immunization or when it was delivered as a subunit protein vaccine formulated either with the MF59 adjuvant or by i ncorporation into immune-stimulating complexes (ISCOMs) were compared. Viru s-neutralizing antibodies (NA) against HIV-1(SF2) reached similar titers in the two rgp120(SF2) protein-immunized groups, but the responses showed dif ferent kinetics, while NA were delayed and their levels were low in the DNA -immunized animals. Antigen-specific gamma interferon (IFN-gamma) T-helper (type 1-like) responses were detected in the DNA-immunized group, but only after the fourth immunization, and the rgp120/MF59 group generated both IFN -gamma and interleukin-4 (IL-4) (type 2-like) responses that appeared after the third immunization. In contrast, rp120/ISCOM-immunized animals rapidly developed marked IL-2, IFN-gamma (type 1-like), and IL-4 responses that pe aked after the second immunization. To determine which type of immune respo nses correlated with protection from infection, all animals were challenged intravenously with 50 50% infective doses of a rhesus cell-propagated, in vivo-titrated stock of a chimeric simian immunodeficiency virus-HIVSF13 con struct. Protection was observed in the two groups receiving the rgp120 subu nit vaccines. Half of the animals in the ISCOM group were completely protec ted from infection. In other subunit vaccinees there was evidence by multip le assays that virus detected at 2 weeks postchallenge was effectively clea red. Early induction of potent type 1- as well as type 2-like T-helper resp onses induced the most-effective immunity.