Anti-idiotype antibodies that mimic a conserved aquatic birnavirus epitope induce neutralizing antibodies and bind to fish cells with inhibition of virus replication

Abstract

Polyclonal anti-idiotype (anti-Id) antibodies were prepared in rats against a monoclonal antibody (MAb AS-1) which defines a highly conserved neutralization epitope on virion protein 2 (VP2) of Serogroup A aquatic birnaviruses. Anti-mouse IgG cross-reactive antibodies were removed from rat sera by adsorption to an affinity column of normal mouse IgG and further punfied by subsequent adsorption to and elution from an affinity column coupled with MAb AS-1. Confirmation that these anti-Id antibodies were directed against the paratope of MAb AS-1 and molecularly mimicked the virus epitope was demonstrated in a variety of assays. Anti-Id antibodies reacted in enzyme-linked immunosorbent assay (ELISA) with both whole MAb AS-1 IgG and F(ab);, fragments, but &d not react with 2 unrelated mouse IgGs or F(ab);, fragments. Anti-Id antibodies blocked binding of virus to MAb AS-1 in a dose-dependent manner with 100% inhibition at the highest concentration. Similarly, virus inhibited anti-Id/i&otype binding by 60 %. Furthermore, anti-Id antibodies inhibited the ability of MAb AS-1 to neutralize virus in plaque reduction assays. Anti-ld antibodies induced the production of virus neutralizing antibodies in mice. Anti-Id antibodies also were used to show that the AS-1 epitope is a presumptive cell attachment site on the virus which recognizes and binds to specific cell receptors Anti-Id antibodies were shown to bind to a variety of both salmonid and non-salmonid fish cell cultures. Pretreatment of fish cell cultures with virus inhibited (28 to 50%) binding of anti-ld antibodies. Treatment of fish cell cultures with anti-Id antibodies also resulted in a decrease (98%) in the yield of progeny virus compared with replication of the virus in untreated cells or cells treated with normal rat immunoglobulin.

Immune Modulatory Potential of Anti-idiotype Antibodies as a Surrogate of Foot-and-Mouth Disease Virus Antigen

“…The non-paratope-specific Ab2 may not block by viral attachment except for nonspecific stearic hindrance. As evidenced by previous studies by Chiang and Nicholson, a 60% level of inhibition of viral attachment suggests a high percentage of β Ab2 mimicking the viral antigen ( 17 ). In the present study, the range of mean Ab titer recorded was 73% to 81%, which correlates with results reported from previous studies, as only the β Ab2 can mimic viral antigens to give Ab titers.…”