THE HUMANIZED SEVERE COMBINED IMMUNODEFICIENT MOUSE AS A MODEL FOR PRIMARY HUMAN HUMORAL RESPONSE AGAINST HIV-1 PEPTIDES

Adequate animal models for the study of human immunodeficiency virus ( HIV) infection are important for the analysis of specific cellular and humoral immune responses. Humanized severe combined immunodeficiency (SCID) mice can be constructed either by injecting human peripheral bl ood lymphocytes (hu-PBL-SCID) or by transplanting human fetal tissues - liver, thymus and bone fragments - (SCID-hu) into these mice. Such a nimals can produce human immunoglobulins and SCID-hu mice exhibit circ ulating T and B lymphocytes of human origin. These humanized mice were injected with immunogenic HIV peptides and the specific humoral respo nse was studied. A human antibody response was obtained after de novo contact with HIV1 peptides p583 and p642, from gp41. In SCID-hu mice, a primary, then a secondary response were demonstrated to occur with 2 25 mg/l of human immunoglobulin (Ig)M and 300-1860 mg/l human IgG. Whe n tested in ELISA, these human antibodies recognized specifically both the immunization peptides and the HIV1 antigens. The antibody respons e was obviously of a primary nature since the human cells derived from naive fetal cells. When SCID mice received intraperitoneal injections of human peripheral blood lymphocytes pre-incubated in vitro with pep tide p583 for 1 week, and when the resulting hu-PBL-SCID mice were inj ected with the same peptide, only IgM anti-HIV antibodies were produce d (372-424 mg/l) and the switch to IgG antibodies did not occur. This model may provide a means to produce human monoclonal antibodies to HI V and to check candidate HIV vaccines,