Cross-neutralization of cutaneous and mucosal Papillomavirus types with anti-sera to the amino terminus of L2

Abstract

Vaccination with papillomavirus L2 has been shown to induce neutralizing antibodies that protect against homologous type infection and cross-neutralize a limited number of genital HPVs. Surprisingly, we found that antibodies to bovine papillomavirus (BPV1) L2 amino acids 1-88 induced similar titers of neutralizing antibodies against Human papillomavirus (HPV)16 and 18 and BPV1 pseudoviruses and also neutralized HPV11 native virions. These antibodies also neutralized each of the other pseudovirus types tested, HPV31, HPV6 and Cottontail rabbit papillomavirus (CRPV) pseudoviruses, albeit with lower titers. HPV16, HPV18, HPV31, HPV6 and CRPV L2 anti-sera also displayed some cross-neutralization, but the titers were lower and did not encompass all pseudoviruses tested. This study demonstrates the presence of broadly cross-neutralizing epitopes at the N-terminus of L2 that are shared by cutaneous and mucosal types and by types that infect divergent species. BPV1 L2 was exceptionally effective at inducing cross-neutralizing antibodies to these shared epitopes.

Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection

“…Third, furin cleavage of L2 could prevent exposure of L2-specific neutralizing B cell epitopes until the capsids are internalized. Consistent with this latter conjecture, the broadly cross-type neutralization epitopes of L2 map near the furin cleavage site (33). L2 immunogens exposing this cleavage site might be particularly effective at inducing broadly cross-neutralizing PV antibodies.…”

Human α-defensins block papillomavirus infection

“…[16][17][18][19]. Except for HPV5 (see below), all PsVs carried a 7.9-kb GFP reporter plasmid, p8fwB.…”

Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

“…Protection is mediated by neutralizing antibodies, and the work of several laboratories has identified cross-neutralizing epitopes (10)(11)(12)(13)(14)(15)(16)(17)(18). We have previously reported that monoclonal antibody RG-1, which is specific for residues 17-36 of L2 from HPV16, neutral-izes both HPV16 and HPV18 and protects naïve mice from challenge with HPV16 (12).…”