Induction of neutralizing antibodies to papillomaviruses by anti-idiotypic antibodies

Anti-idiotypic antibodies (anti-Ids) were generated against three mouse monoclonal antibodies (MAbs) which neutralized three different papillomaviruses. The neutralizing MAbs (N-MAbs) were generated against infectious human papillomavirus type 11 (HPV-11), cottontail rabbit papillomavirus (CRPV), and bovine papillomavirus type 1 (BPV-1), and all recognized surface conformational epitopes that were lost upon denaturation of the virions. The polyclonal anti-Ids were screened in an ELISA using a panel of 10 N-MAbs (4 HPV-11 neutralizing, 5 CRPV neutralizing, and 1 BPV-1 neutralizing), and cross-reactive idiotypic reactivity was observed. Affinity-purified anti-H11.B2 (HPV-11 N-MAb) cross-reacted with the 3 other HPV-11 N-MAbs, was unreactive to a nonneutralizing HPV-11 MAb and all 5 CRPV N-MAbs, but surprisingly was reactive to the BPV-1 N-MAb. in contrast, affinity-purified anti-CRPV-1A (CRPV N-MAb) reacted with all 5 CRPV N-MAbs, but not with any other MAb. Affinity-purified anti-B1.A1 (BPV-1 N-MAb) also showed unexpected cross-reactivity with the 4 HPV-11 N-MAbs, but not with any of the CRPV N-MAbs. Two of the three polyclonal rabbit anti-Ids induced strong anti-viral antibody responses (including virus-neutralizing antibodies) in BALB/c mice following immunization. The results indicate that within a mouse strain, papillomavirus-neutralizing antibodies share cross-reactive idiotopes that group the N-MAbs into several subsets. One group includes the CRPV N-MAbs, and another group includes N-MAbs directed to apparently unrelated papillomaviruses, including HPV-11, BPV-1, and possibly HPV-6.