Assessment of the serological relatedness of genital human papillomaviruses by hemagglutination inhibition

Abstract

To assess the potential for cross-protection among genital human papillomavirus (HPV) types in virus-like particle (VLP)-based vaccinations, inhibition of HPV VLP-mediated hemagglutination by rabbit antisera raised against HPV type 6b (HPV-6b), HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, and HPV-45 was analyzed. Only highly homologous types (HPV-6b and HPV-11, and HPV-18 and HPV-45) exhibited detectable serological cross-reaction for the class of antibodies that inhibit virion-to-cell surface binding. However, analysis of neutralizing monoclonal antibodies to several animal and human papillomaviruses indicated that over half of these antibodies do not prevent cell surface binding, but these latter antibodies do not appear to be more cross-reactive in enzyme-linked immunosorbent assays than those that mediate inhibition of hemagglutination. The data strongly suggest that while there may be limited cross-protection between highly (>85% L1 amino acid identity) homologous types, protection by HPV VLP-based vaccines will be predominantly type specific.

Safety and immunogenicity of BPV‐1 L1 virus‐like particles in a dose‐escalation vaccination trial in horses

“…Antibody responses to VLP vaccination are mainly type-restricted, yet cross-neutralising immune responses have been observed that confer partial cross-protection to closely related HPV types in human vaccine trials (Roden et al 1996;Pastrana et al 2005;Villa et al 2005). BPV-1 and BPV-2 are closely related genotypes.…”

Patterns of genotype distribution in multiple human papillomavirus infections

“…Populations at high risk for cervical cancer, and populations with high rates of human immunodeficiency virus (HIV) infection, tend to show higher proportions of infections with multiple types, as compared with populations that do not belong to these risk groups [4]. Epidemiological studies suggest that the immune response to HPV is type-specific [5], but there is no agreement concerning the influence of infection with multiple HPV types on cervical carcinogenesis. According to Trottier et al [6], infections with multiple HPV types seem to act synergically in cervical carcinogenesis.…”

Cervical secretory immunoglobulin A to human papillomavirus type 16 (HPV16) from HPV16-infected women inhibit HPV16 virus-like particles-induced hemagglutination of mouse red blood cells

“…Antibodies from 44.0% of patients inhibited HPV16 VLP-induced hemagglutination, suggesting that they recognize conformational epitopes on the capsid proteins. Hemagglutination inhibition assay has been regarded as a surrogate method to evaluate the neutralization potential of antibodies [11]. As far as we are aware this is the ¢rst report of the use of such methodology for the study of human secretory antibodies to HPV16.…”

“…However, not all of them are suit-able for the study of large numbers of human samples. Inhibition of HPV virus-like particles (VLP)-induced hemagglutination of mouse red blood cells (RBCs) has been used as a surrogate assay to evaluate neutralizing responses [11], and provides a useful methodology for the study of human cervical mucus samples.…”