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Pre-clinical immunogenicity of human papillomavirus alpha-7 and alpha-9 major capsid proteins.

Bissett SL, Mattiuzzo G, Draper E, Godi A, Wilkinson DE, Minor P, Page M, Beddows S - Vaccine (2014)

Bottom Line: The majority antibody response against L1 VLP was type-specific, as expected, but several instances of robust cross-neutralization were nevertheless observed including between HPV33 and HPV58 within the Alpha-9 species and between HPV39, HPV59 and HPV68 in the Alpha-7 species.Competition of HPV31 and HPV33 cross-neutralizing antibodies in the tetravalent sera confirmed that these antibodies originated from HPV16 and HPV58 VLP, respectively, and suggested that they represent minority specificities within the antibody repertoire generated by the immunizing antigen.These data improve our understanding of the antigenic diversity of the L1 protein per se and may inform the rational design of a next generation vaccine formulation based upon empirical data.

View Article: PubMed Central - PubMed

Affiliation: Virus Reference Department, Public Health England, London, UK.

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Related in: MedlinePlus

Phylogenetic relationship between the major capsid proteins of the Alpha-7 and Alpha-9 genotypes. (A) Amino acid sequences of the L1 major capsid proteins representing both VLP and pseudoviruses of the Alpha-7 (HPV18, HPV39, HPV45, HPV59, HPV68) and Alpha-9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58) genotypes and the control BPV [20]. Radial representation of NJ tree with branches having less than 80% bootstrap (n = 500 replicates) support (HPV35 and HPV59) indicated in gray. (B) Heatmap representation of inter-genotype genetic distances based upon external surface loops only or remaining (non-loop) backbone for the L1 proteins of the indicated Alpha-7 and Alpha-9 genotypes. Key indicates heatmap gradient.
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fig0015: Phylogenetic relationship between the major capsid proteins of the Alpha-7 and Alpha-9 genotypes. (A) Amino acid sequences of the L1 major capsid proteins representing both VLP and pseudoviruses of the Alpha-7 (HPV18, HPV39, HPV45, HPV59, HPV68) and Alpha-9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58) genotypes and the control BPV [20]. Radial representation of NJ tree with branches having less than 80% bootstrap (n = 500 replicates) support (HPV35 and HPV59) indicated in gray. (B) Heatmap representation of inter-genotype genetic distances based upon external surface loops only or remaining (non-loop) backbone for the L1 proteins of the indicated Alpha-7 and Alpha-9 genotypes. Key indicates heatmap gradient.

Mentions: A phylogenetic representation of the amino acid sequences used for the Alpha-7 and Alpha-9 VLP and pseudovirus L1 proteins demonstrates the close relationship between certain genotypes within each of these two species groups (Fig. 3A). The amino acid sequences of the surface-exposed loops [38,39] are likely to contribute to the antigenic similarity and distinction between HPV genotypes (Fig. 3B). The median intra-species group surface-exposed loop genetic distances for these Alpha-7 and Alpha-9 L1 sequences were similar at 0.19 (IQR 0.15–0.20) and 0.24 (0.18–0.24), respectively (p = 0.146), and substantially lower than the median inter-species genetic distance of 0.37 (0.35–0.40; p < 0.001). Within the Alpha-9 species group, the antigenic similarity between HPV33 and HPV58 is perhaps reflected in the low genetic distance between these genotypes. The apparent antigenic relationship between HPV39 and HPV59 within the Alpha-7 species group, however, is not similarly reflected by low genetic distances.


Pre-clinical immunogenicity of human papillomavirus alpha-7 and alpha-9 major capsid proteins.

Bissett SL, Mattiuzzo G, Draper E, Godi A, Wilkinson DE, Minor P, Page M, Beddows S - Vaccine (2014)

Phylogenetic relationship between the major capsid proteins of the Alpha-7 and Alpha-9 genotypes. (A) Amino acid sequences of the L1 major capsid proteins representing both VLP and pseudoviruses of the Alpha-7 (HPV18, HPV39, HPV45, HPV59, HPV68) and Alpha-9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58) genotypes and the control BPV [20]. Radial representation of NJ tree with branches having less than 80% bootstrap (n = 500 replicates) support (HPV35 and HPV59) indicated in gray. (B) Heatmap representation of inter-genotype genetic distances based upon external surface loops only or remaining (non-loop) backbone for the L1 proteins of the indicated Alpha-7 and Alpha-9 genotypes. Key indicates heatmap gradient.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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fig0015: Phylogenetic relationship between the major capsid proteins of the Alpha-7 and Alpha-9 genotypes. (A) Amino acid sequences of the L1 major capsid proteins representing both VLP and pseudoviruses of the Alpha-7 (HPV18, HPV39, HPV45, HPV59, HPV68) and Alpha-9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58) genotypes and the control BPV [20]. Radial representation of NJ tree with branches having less than 80% bootstrap (n = 500 replicates) support (HPV35 and HPV59) indicated in gray. (B) Heatmap representation of inter-genotype genetic distances based upon external surface loops only or remaining (non-loop) backbone for the L1 proteins of the indicated Alpha-7 and Alpha-9 genotypes. Key indicates heatmap gradient.
Mentions: A phylogenetic representation of the amino acid sequences used for the Alpha-7 and Alpha-9 VLP and pseudovirus L1 proteins demonstrates the close relationship between certain genotypes within each of these two species groups (Fig. 3A). The amino acid sequences of the surface-exposed loops [38,39] are likely to contribute to the antigenic similarity and distinction between HPV genotypes (Fig. 3B). The median intra-species group surface-exposed loop genetic distances for these Alpha-7 and Alpha-9 L1 sequences were similar at 0.19 (IQR 0.15–0.20) and 0.24 (0.18–0.24), respectively (p = 0.146), and substantially lower than the median inter-species genetic distance of 0.37 (0.35–0.40; p < 0.001). Within the Alpha-9 species group, the antigenic similarity between HPV33 and HPV58 is perhaps reflected in the low genetic distance between these genotypes. The apparent antigenic relationship between HPV39 and HPV59 within the Alpha-7 species group, however, is not similarly reflected by low genetic distances.

Bottom Line: The majority antibody response against L1 VLP was type-specific, as expected, but several instances of robust cross-neutralization were nevertheless observed including between HPV33 and HPV58 within the Alpha-9 species and between HPV39, HPV59 and HPV68 in the Alpha-7 species.Competition of HPV31 and HPV33 cross-neutralizing antibodies in the tetravalent sera confirmed that these antibodies originated from HPV16 and HPV58 VLP, respectively, and suggested that they represent minority specificities within the antibody repertoire generated by the immunizing antigen.These data improve our understanding of the antigenic diversity of the L1 protein per se and may inform the rational design of a next generation vaccine formulation based upon empirical data.

View Article: PubMed Central - PubMed

Affiliation: Virus Reference Department, Public Health England, London, UK.

Show MeSH
Related in: MedlinePlus