Polyvalent envelope glycoprotein vaccine elicits a broader neutralizing antibody response but is unable to provide sterilizing protection against heterologous Simian/human immunodeficiency virus infection in pigtailed macaques

The great difficulty in eliciting broadly cross-reactive neutralizing antib odies (NAbs) against human immunodeficiency virus type 1 (HIV-l) isolates h as been attributed to several intrinsic properties of their viral envelope glycoprotein, including its complex quaternary structure, extensive glycosy lation, and marked genetic variability. Most previously evaluated vaccine c andidates have utilized envelope glycoprotein from a single virus isolate. Here we compare the breadth of NAb and protective immune response following vaccination of pigtailed macaques with envelope protein(s) derived from ei ther single or multiple viral isolates. Animals were challenged with Simian /human immunodeficiency virus strain DH12 (SHTVDH12) following priming with recombinant vaccinia virus(es) expressing gp160(s) and boosting with gp120 protein(s) from (1) LAI, RIF, 89.6, ADS, and Bal (Polyvalent); (ii) LAI, R F, 89.6, AD8, Bal, and DH12 (Polyvalent-DH12); (iii) 89.6 (Monovalent-89.6) ; and (iv) DH12 (Monovalent-DH12). Animals in the two polyvalent vaccine gr oups developed NAbs against more HIV-1 isolates than those in the two monov alent vaccine groups (P = 0.0054). However, the increased breadth of respon se was directed almost entirely against the vaccine strains. Resistance to SHIVDH12 strongly correlated with the level of NAbs directed against the vi rus on the day of challenge (P = 0.0008). Accordingly, the animals in the M onovalent-DH12 and Polyvalent-DH12 vaccine groups were more resistant to th e SHIVDH12 challenge than the macaques immunized with preparations lacking a DH12 component (viz. Polyvalent and Monovalent-89.6) (P = 0.039). Despite the absence of any detectable NAb, animals in the Polyvalent vaccine group , but not those immunized with Monovalent-89.6, exhibited markedly lower le vels of plasma virus than those in the control group, suggesting a superior cell-mediated immune response induced by the polyvalent vaccine.