Identification of the mimotopes within the major capsid protein L1 of human papillomavirus types 18 and 45, using neutralizing monoclonal antibodies

ABSTRACT To characterize epitopes on human papillomavirus (HPV) virus-like particles (VLPs), a panel of mutated HPV-16 VLPs was created. Each mutated VLP had residues substituted from HPV-31 or HPV-52 L1 sequences to the HPV-16 L1 backbone. Mutations were created on the HPV-31 and −52 L1 proteins to determine if HPV-16 type-specific recognition could be transferred. Correct folding of the mutated proteins was verified by resistance to trypsin digestion and by binding to one or more conformation-dependent monoclonal antibodies. Several of the antibodies tested were found to bind to regions already identified as being important for HPV VLP recognition (loops DE, EF, FG, and HI). Sequences at both ends of the long FG loop (amino acids 260 to 290) were required for both H16.V5 and H16.E70 reactivity. A new antibody-binding site was discovered on the C-terminal arm of L1 between positions 427 and 445. Recognition of these residues by the H16.U4 antibody suggests that this region is surface exposed and supports a recently proposed molecular model of HPV VLPs.

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Human papillomavirus type 16 infection of the cervix: a comparison of differing DNA detection modes and the use of monoclonal antibodies against the major capsid protein.

Sexually Transmitted Infections ◽

10.1136/sti.67.2.87 ◽

1991 ◽

Vol 67 (2) ◽

pp. 87-91

Author(s):

C J Lacey ◽

M Wells ◽

R I Macdermott ◽

P E Gibson

Keyword(s):

Monoclonal Antibodies ◽

Human Papillomavirus ◽

Capsid Protein ◽

Major Capsid Protein ◽

Dna Detection ◽

Human Papillomavirus Type 16

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Reactivities of Polyclonal and Monoclonal Antibodies Raised to the Major Capsid Protein of Human Papillomavirus Type 16

Journal of General Virology ◽

10.1099/0022-1317-70-1-69 ◽

1989 ◽

Vol 70 (1) ◽

pp. 69-77 ◽

Cited By ~ 16

Author(s):

D. Patel ◽

P. S. Shepherd ◽

J. A. Naylor ◽

D. J. McCance

Keyword(s):

Monoclonal Antibodies ◽

Human Papillomavirus ◽

Capsid Protein ◽

Major Capsid Protein ◽

Human Papillomavirus Type 16

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Head-to-Head Comparison of Modular Vaccines Developed Using Different Capsid Virus-Like Particle Backbones and Antigen Conjugation Systems

Vaccines ◽

10.3390/vaccines9060539 ◽

2021 ◽

Vol 9 (6) ◽

pp. 539

Author(s):

Laurits Fredsgaard ◽

Louise Goksøyr ◽

Susan Thrane ◽

Kara-Lee Aves ◽

Thor G. Theander ◽

...

Keyword(s):

Immune Response ◽

Human Papillomavirus ◽

Immune Responses ◽

Capsid Protein ◽

Major Capsid Protein ◽

Molecular Scaffolds ◽

Conjugation System ◽

Virus Like Particles ◽

Virus Like Particle ◽

Specific Igg

Capsid virus-like particles (cVLPs) are used as molecular scaffolds to increase the immunogenicity of displayed antigens. Modular platforms have been developed whereby antigens are attached to the surface of pre-assembled cVLPs. However, it remains unknown to what extent the employed cVLP backbone and conjugation system may influence the immune response elicited against the displayed antigen. Here, we performed a head-to-head comparison of antigen-specific IgG responses elicited by modular cVLP-vaccines differing by their employed cVLP backbone or conjugation system, respectively. Covalent antigen conjugation (i.e., employing the SpyTag/SpyCatcher system) resulted in significantly higher antigen-specific IgG titers compared to when using affinity-based conjugation (i.e., using biotin/streptavidin). The cVLP backbone also influenced the antigen-specific IgG response. Specifically, vaccines based on the bacteriophage AP205 cVLP elicited significantly higher antigen-specific IgG compared to corresponding vaccines using the human papillomavirus major capsid protein (HPV L1) cVLP. In addition, the AP205 cVLP platform mediated induction of antigen-specific IgG with a different subclass profile (i.e., higher IgG2a and IgG2b) compared to HPV L1 cVLP. These results demonstrate that the cVLP backbone and conjugation system can individually affect the IgG response elicited against a displayed antigen. These data will aid the understanding and process of tailoring modular cVLP vaccines to achieve improved immune responses.

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