Recombinant human CD4 elicits antibody responses different in epitope specificity from those that cellular CD4...

Recombinant proteins have been proposed as subunit vaccines for many viral, bacterial and parasitic diseases, to reduce adverse side effects associated with inactivated or attenuated vaccines. Yet little is known about the comparative immunogenicity of recombinant proteins vs native forms present in cells or on organisms, and little is known about comparisons of the specificities of such immune responses. In another observation about differing forms of an antigen, about 10% of AIDS patients have anti-CD4 autoantibodies recognizing sites seen in recombinant CD4 (rCD4) but not present on cell surface CD4. We have analyzed antibody responses of mice to human CD4 when presented in recombinant or in cellular form. The response to the whole molecule was examined, as well as the responses to two sites within the molecule. In addition, any effect of immune response genes in the responding animal was sought, which might potentially restrict or modify any response to CD4. Mice immunized with rCD4 generated a large response to rCD4, but a lower response to the cell surface form, implying that additional sites are recognized on the recombinant form that are not recognized in the cellular form. Mice immunized with cells containing surface CD4 had high titers of antibody reactive with whole cells, of which only a small portion was reactive with rCD4. Titers on rCD4 are much lower for these mice than in rCD4-immunized mice. Both forms of CD4 induced antibodies to the gp120 binding site with comparable efficiency. For another site in domain 3 or 4 of CD4, cellular CD4 induced antibodies more frequently than the recombinant form. Immune response gene differences did not play a detectable role in the anti-CD4 response.