FINE ANALYSIS OF HUMORAL ANTIBODY-RESPONSE TO ENVELOPE GLYCOPROTEIN OF SIV IN INFECTED AND VACCINATED MACAQUES

To characterize the serological response to SIV envelope, induced by v accination with different envelope immunogens or by SIV infection, pla sma samples from 11 cynomolgus macaques infected with simian immunodef iciency virus (SIV) and from 16 macaques vaccinated with three differe nt recombinant envelope proteins were analyzed by (1) ELISA, using a v ariety of antigens including overlapping peptides encompassing the ent ire sequence of the envelope protein of SIV, and (2) competition assay s, using neutralizing monoclonal antibodies to SIV gp120. Seven region s of SIV envelope were predicted to be antigenic. Peptides representin g four of these, in the second and third variable regions (V2 and V3) and the fourth constant (C4) region of gp120 and the Gnann region of g p41, were recognized by the majority of sera from infected and vaccina ted animals. Additional antigenic regions were identified in the first and fourth variable domains (V1 and V4) and the carboxy terminus (C5) of gp120 and in three additional regions of gp41. Most infected and v accinated animals made antibodies that competed with the binding of th e three conformational MAbs. Among the vaccinated groups, antibodies i nduced by vaccination with precursor glycoproteins (gp148 or gp160) re cognized several additional gp120 epitopes when compared with antibodi es induced by external glycoprotein gp130. Sera from infected animals showed a more restricted gp120 response (17 of 46 peptides recognized) compared to animals vaccinated with precursor glycoproteins (31 pepti des recognized). The converse was true for antibodies to gp41. Sera fr om animals vaccinated with recombinant gp140, produced in insect cells , were the only group that failed to compete with the binding of confo rmational MAbs. Finally, the development of antibodies to specific epi topes of gp120 and gp41 revealed differences between long-term survivo rs and nonsurvivors, implying that responses to specific epitopes may be important in conferring resistance to disease progression.