ANTIBODY NEUTRALIZATION-RESISTANT PRIMARY ISOLATES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Although typical primary isolates of human immunodeficiency virus type 1 (HIV-1) are relatively neutralization resistant, three human monocl onal antibodies and a small number of HIV-1(+) human sera that neutral ize the majority of isolates have been described. The monoclonal antib odies (2G12, 2F5, and b12) represent specificities that a putative vac cine should aim to elicit, since in vitro neutralization has been corr elated with protection against primary viruses in animal models. Furth ermore, a neutralization escape mutant to one of the antibodies (b12) selected in vitro remains sensitive to neutralization by the other two (2G12 and 2F5) (H. Mo, L. Stamatatos, J. E. Ip, C. F. Barbas, P. W. H . I. Parren, D. R. Burton, J. P. Moore, and D. D. Ho, J. Virol; 71:686 9-6874, 1997), supporting the notion that eliciting a combination of s uch specificities would be particularly advantageous. Here, however, w e describe a small subset of viruses, mostly pediatric, which show a h igh level of neutralization resistance to all three human monoclonal a ntibodies and to two broadly neutralizing sera. Such viruses threaten antibody-based antiviral strategies, and the basis for their resistanc e should be explored.