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Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31 Represent a Single L1 Serotype
Sara L Bissett1, Anna Godi1, Maxime J J Fleury2
1Virus Reference Department, Public Health England, London, United Kingdom.
Unlabelled:
We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) representing the three HPV31 variant lineages, variant lineages A, B, and C, exhibited comparable particle-to-infectivity ratios and morphologies. Lineage-specific L1L2 PsVs demonstrated subtle differences in susceptibility to neutralization by antibodies elicited following vaccination or preclinical L1 virus-like particle (VLP) immunization or by monoclonal antibodies; however, these differences were generally of a low magnitude. These data indicate that the diagnostic lineage-specific single nucleotide polymorphisms within the HPV31 capsid genes have a limited effect on L1 antibody-mediated neutralization and that the three HPV31 variant lineages belong to a single L1 serotype. These data contribute to our understanding of HPV L1 variant antigenicity.
Importance:
The virus coat (capsid) of the human papillomavirus contains major (L1) and minor (L2) capsid proteins. These proteins facilitate host cell attachment and viral infectivity and are the targets for antibodies which interfere with these events. In this study, we investigated the impact of naturally occurring variation within these proteins upon susceptibility to viral neutralization by antibodies induced by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit similar susceptibility to antibody-mediated neutralization and that for the purposes of L1 VLP-based vaccines, these variant lineages represent a single serotype.
Insights
Naturally occurring variations in human papillomavirus (HPV) genotype 31 capsid proteins (L1 and L2) have minimal impact on antibody neutralization. These HPV31 variants represent a single L1 serotype, crucial for vaccine development.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- The human papillomavirus (HPV) capsid, composed of major (L1) and minor (L2) proteins, is essential for viral entry and infectivity.
- These capsid proteins are primary targets for neutralizing antibodies, forming the basis for L1 virus-like particle (VLP) vaccines.
- Naturally occurring genetic variations exist within HPV genotypes, potentially affecting capsid antigenicity and vaccine efficacy.
Purpose of the Study:
- To investigate the impact of naturally occurring variations in HPV genotype 31 (HPV31) L1 and L2 capsid proteins on antigenicity.
- To determine if HPV31 variant lineages affect susceptibility to antibody-mediated neutralization.
- To assess if HPV31 variants represent a single serotype for L1 VLP-based vaccine considerations.
Main Methods:
- Production of L1L2 pseudoviruses (PsVs) representing three HPV31 variant lineages (A, B, and C).
- Assessment of particle-to-infectivity ratios and morphologies of lineage-specific PsVs.
- Evaluation of PsV neutralization susceptibility using antibodies from vaccination, L1 VLP immunization, and monoclonal antibodies.
Main Results:
- HPV31 variant lineages A, B, and C exhibited comparable particle-to-infectivity ratios and morphologies.
- Lineage-specific PsVs showed only subtle, low-magnitude differences in neutralization susceptibility to various antibodies.
- Single nucleotide polymorphisms within HPV31 capsid genes had a limited effect on L1 antibody-mediated neutralization.
Conclusions:
- The three HPV31 variant lineages demonstrate a single L1 serotype.
- Naturally occurring variations in HPV31 L1 and L2 capsid proteins have a limited impact on antibody neutralization.
- These findings support the classification of HPV31 variants as a single serotype for L1 VLP vaccine purposes.
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