Identification of species-specific and cross-reactive epitopes in human polyomavirus capsids using monoclonal antibodies

The human antibody response to polyomavirus capsid proteins is not well characterized. Recombinant BK virus (BKV), JC virus (JCV) and simian virus 40 (SV40) virus-like particles (VLP) were produced in a baculovirus system, and mouse monoclonal antibodies (mAbs) to these proteins were generated using standard methods. Nine of 12 BKV mAbs showed neutralizing activity. The non-neutralizing antibodies also bound BKV pseudocapsids in an ELISA binding assay. Most antibodies recognized conformational species-specific epitopes, but several exceptions were found: (i) BKV mAb BK-F11 cross-reacted with a linear buried epitope common to both JCV and SV40 pseudocapsids, (ii) two of six JCV antibodies (JC-6.7 and JC-7.9) and two of 13 SV40 antibodies (VP1-H2 and VP1-I2) recognized linear buried epitopes common to all three viruses and (iii) SV40 antibody VP1-E5 recognized a linear surface epitope on JCV pseudocapsids.