Induction,via Immunization with a Monoclonal Antiidiotypic Antibody,of Viral Envelope Specific Ab3 Antisera That Neutralize Retrovirus Infectivity

We have developed five mouse monoclonal antiidiotypic antibodies to the 35/56 (Ab1) rat monoclonal that neutralizes retroviral infectivity by binding to the gp70^f epitope of murine leukemia retrovirus. The anti-Id nature of these five Ab2s was evidenced by their inability to react with a panel of six other rat IgG_2aκ monoclonals isotype-matched to the 35/56 anti-gp70^f mAb1, including two to the distinct epitopes "g" and "h" of gp70, or to normal rat IgG_2a. On the basis of several competition assays four mAb2 were clearly either directed to the paratope of anti-gp70^f mAb1 (.1C7,.1B, and.E) or not (.A, representing a noninternal image Ab2α anti-Id). The P3E8 mAb2 was difficult to classify. Based on relative efficiency in these assays,.1C7 was chosen for further study, and upon injection was able to induce Ab3 responses in C57BL/6, BALB/c, and CBA mice. The fact that the Ab3 activity was detected in a competitive ELISA in which the hyperimmune antisera blocked the binding of Ab1 to Ab2, plus the ability to raise Ab3 neutralizing antibodies in three different mouse strains were consistent with.1C7 as an internal image Ab2β anti-Id. These results thus indicate the potential for internal-image monoclonal antiidiotypic antibody-based vaccines for retroviral diseases.