scholarly journals Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58

2014 ◽  
Vol 21 (4) ◽  
pp. 587-593 ◽  
Author(s):  
Martha J. Brown ◽  
Hanna Seitz ◽  
Victoria Towne ◽  
Martin Müller ◽  
Adam C. Finnefrock
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Cervical Cancers ◽  
Hpv Types ◽  
Oncogenic Hpv ◽  
Neutralizing Epitopes ◽  
Selection Of

ABSTRACTHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic.

scholarly journals Human papillomavirus genotypes in cervical cancers in Mozambique

2004 ◽  
Vol 85 (8) ◽  
pp. 2189-2190 ◽  
Author(s):  
Pontus Naucler ◽  
Flora Mabota da Costa ◽  
Otto Ljungberg ◽  
Antonio Bugalho ◽  
Joakim Dillner
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Case Series ◽  
Cervical Neoplasia ◽  
Consecutive Case ◽  
Substantial Impact ◽  
Cervical Cancers ◽  
Hpv Types ◽  
Oncogenic Hpv

The distribution of human papillomavirus (HPV) types in cervical cancers is essential for design and evaluation of HPV type-specific vaccines. To follow up on a previous report that HPV types 35 and 58 were the dominant HPV types in cervical neoplasia in Mozambique, the HPV types in a consecutive case series of 74 invasive cervical cancers in Mozambique were determined. The most common worldwide major oncogenic HPV types 16 and 18 were present in 69 % of cervical cancers, suggesting that a vaccine targeting HPV-16 and -18 would have a substantial impact on cervical cancer also in Mozambique.

scholarly journals Molecular Characterization of High-Risk Human Papillomavirus in Women in Bobo-Dioulasso, Burkina Faso

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Ina Marie Angèle Traore ◽  
Théodora Mahoukèdè Zohoncon ◽  
Adama Dembele ◽  
Florencia W. Djigma ◽  
Dorcas Obiri-Yeboah ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
University Hospital ◽  
Cervical Cancers ◽  
High Prevalence ◽  
Bobo Dioulasso ◽  
Hpv Types ◽  
High Risk Hpv ◽  
Hpv 18

High-risk human papillomavirus (HPV) is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of35.3±8.1years. The prevalence of infection by high-risk HPV types was 25.4% (46/181). The most common high-risk HPV genotypes were HPV 39 (18.5%), HPV 52 (16.7%), HPV 18 (14.8%), and HPV 35 (13.0%). HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine.

Impact of the B.1.1.7 variant on neutralizing monoclonal antibodies recognizing diverse epitopes on SARS–CoV–2 Spike

2021 ◽  
Author(s):  
Carl Graham ◽  
Jeffrey Seow ◽  
Isabella Huettner ◽  
Hataf Khan ◽  
Neophytos Kouphou ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Infectious Virus ◽  
Antigenic Drift ◽  
Host Cells ◽  
Receptor Binding Domain ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Neutralizing Epitopes

The interaction of the SARS–CoV–2 Spike receptor binding domain (RBD) with the ACE2 receptor on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS–CoV–2 variants has revealed mutations arising in the RBD, the N–terminal domain (NTD) and S2 subunits of Spike. To fully understand how these mutations affect the antigenicity of Spike, we have isolated and characterized neutralizing antibodies targeting epitopes beyond the already identified RBD epitopes. Using recombinant Spike as a sorting bait, we isolated >100 Spike–reactive monoclonal antibodies from SARS–CoV–2 infected individuals. ≈45% showed neutralizing activity of which ≈20% were NTD–specific. None of the S2–specific antibodies showed neutralizing activity. Competition ELISA revealed that NTD–specific mAbs formed two distinct groups: the first group was highly potent against infectious virus, whereas the second was less potent and displayed glycan–dependant neutralization activity. Importantly, mutations present in B.1.1.7 Spike frequently conferred resistance to neutralization by the NTD–specific neutralizing antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes need to be considered when investigating antigenic drift in emerging variants.

Generation and Characterization of a Murine Monoclonal Antibody Specific for the Human T1-Cd5 Molecule

1987 ◽  
Vol 2 (3) ◽  
pp. 143-150 ◽  
Author(s):  
Federico Genzano ◽  
Ada Funaro ◽  
Massimo Alessio ◽  
Lucia B. De Monte ◽  
Graziella Bellone ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
T Lymphocytes ◽  
Membrane Glycoprotein ◽  
Functional Features ◽  
Specific Membrane ◽  
Murine Monoclonal Antibodies ◽  
Selection Of

Murine monoclonal antibodies (MoAbs) have found widespread applications in the characterization of the molecular and functional features of lymphocyte differentiation antigens. The present paper summarizes the results of our work dealing with the production and selection of a murine MoAb recognizing a molecule expressed during the whole differentiative life of T lymphocytes. The MoAb CB01 resulted to be specific for an apparently unique epitope of the T-cell specific membrane glycoprotein T1-CD5.

scholarly journals Neutralization of Human Papillomavirus with Monoclonal Antibodies Reveals Different Mechanisms of Inhibition

2007 ◽  
Vol 81 (16) ◽  
pp. 8784-8792 ◽  
Author(s):  
Patricia M. Day ◽  
Cynthia D. Thompson ◽  
Christopher B. Buck ◽  
Yuk-Ying S. Pang ◽  
Douglas R. Lowy ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Cell Surface ◽  
Binding Sites ◽  
Neutralizing Antibodies ◽  
Hpv Infection ◽  
Heparan Sulfate Proteoglycans ◽  
Hacat Cells ◽  
Block Association

ABSTRACT The mechanisms of human papillomavirus (HPV) neutralization by antibodies are incompletely understood. We have used HPV16 pseudovirus infection of HaCaT cells to analyze how several neutralizing monoclonal antibodies (MAbs) generated against HPV16 L1 interfere with the process of keratinocyte infection. HPV16 capsids normally bind to both the cell surface and extracellular matrix (ECM) of HaCaT cells. Surprisingly, two strongly neutralizing MAbs, V5 and E70, did not prevent attachment of capsids to the cell surface. However, they did block association with the ECM and prevented internalization of cell surface-bound capsids. In contrast, MAb U4 prevented binding to the cell surface but not to the ECM. The epitope recognized by U4 was inaccessible when virions were bound to the cell surface but became accessible after endocytosis, presumably coinciding with receptor detachment. Treatment of capsids with heparin, which is known to interfere with binding to cell surface heparan sulfate proteoglycans (HSPGs), also resulted in HPV16 localization to the ECM. These results suggest that the U4 epitope on the intercapsomeric C-terminal arm is likely to encompass the critical HSPG interaction residues for HPV16, while the V5 and E70 epitopes at the apex of the capsomer overlap the ECM-binding sites. We conclude that neutralizing antibodies can inhibit HPV infection by multiple distinct mechanisms, and understanding these mechanisms can add insight to the HPV entry processes.

scholarly journals Characterization of Neutralizing Antibodies and Identification of Neutralizing Epitope Mimics on the Clostridium botulinum Neurotoxin Type A

2001 ◽  
Vol 67 (7) ◽  
pp. 3201-3207 ◽  
Author(s):  
Han-Chung Wu ◽  
Chia-Tsui Yeh ◽  
Yue-Ling Huang ◽  
Lih-Jeng Tarn ◽  
Chien-Cheng Lung
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Clostridium Botulinum ◽  
Neuromuscular Junctions ◽  
Competitive Inhibition ◽  
Lethal Dose ◽  
Humoral Response ◽  
Type A ◽  
Phage Clone ◽  
Neutralizing Epitopes

ABSTRACT Clostridium botulinum neurotoxin type A (BTx-A) is known to inhibit the release of acetylcholine at the neuromuscular junctions and synapses and to cause neuroparalysis and death. In this study, we have identified two monoclonal antibodies, BT57-1 and BT150-3, which protect ICR mice against lethal doses of BTx-A challenge. The neutralizing activities for BT57-1 and BT150-3 were 103 and 104 times the 50% lethal dose, respectively. Using immunoblotting analysis, BT57-1 was recognized as a light chain and BT150-3 was recognized as a heavy chain of BTx-A. Also, applying the phage display method, we investigated the antibodies' neutralizing B-cell epitopes. These immunopositive phage clones displayed consensus motifs, Asp-Pro-Leu for BT57-1 and Cys-X-Asp-Cys for BT150. The synthetic peptide P4M (KGTFDPLQEPRT) corresponded to the phage-displayed peptide selected by BT57-1 and was able to bind the antibodies specifically. This peptide was also shown by competitive inhibition assay to be able to inhibit phage clone binding to BT57-1. Aspartic acid (D5) in P4M was crucial to the binding of P4M to BT57-1, since its binding activity dramatically decreased when it was changed to lysine (K5). Finally, immunizing mice with the selected phage clones elicited a specific humoral response against BTx-A. These results suggest that phage-displayed random-peptide libraries are useful in identifying the neutralizing epitopes of monoclonal antibodies. In the future, the identification of the neutralizing epitopes of BTx-A may provide important information for the identification of the BTx-A receptor and the design of a BTx-A vaccine.

scholarly journals Detection of Human Papillomavirus Type 31-Neutralizing Antibodies from Naturally Infected Patients by an Assay Based on Intracellular Assembly of Luciferase-Expressing Pseudovirions

2007 ◽  
Vol 15 (1) ◽  
pp. 172-175 ◽  
Author(s):  
Maxime J. J. Fleury ◽  
Antoine Touzé ◽  
Silvia de Sanjosé ◽  
F. Xavier Bosch ◽  
Joellen Klaustermeiyer ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Immunosorbent Assay ◽  
Neutralizing Antibodies ◽  
Neutralization Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Highly Sensitive

ABSTRACT The aim of this study was to develop a highly sensitive human papillomavirus type 31 (HPV31) neutralization assay based on the production of pseudovirions carrying luciferase. Neutralizing antibodies against HPV31 were investigated in a set of HPV31 monoclonal antibodies and in women with evidence of HPV31 infection. Neutralizing antibodies were detected in 78% of subjects with a positive enzyme-linked immunosorbent assay.

scholarly journals Association of serum and mucosal neutralizing antibodies to human papillomavirus type 16 (HPV-16) with HPV-16 infection and cervical disease

2008 ◽  
Vol 89 (4) ◽  
pp. 910-914 ◽  
Author(s):  
Zizipho Z. A. Mbulawa ◽  
Anna-Lise Williamson ◽  
Debbie Stewart ◽  
Jo-Ann S. Passmore ◽  
Lynette Denny ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Neutralizing Antibodies ◽  
Antibody Responses ◽  
Normal Cytology ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Immunodeficiency Virus ◽  
Cervical Disease ◽  
Hpv Types

We investigated neutralizing antibodies to human papillomavirus type 16 (HPV-16) in serum and cervical washes from 84 women with normal cytology or cervical disease. Serum neutralizing antibodies were detected in 78 % of women infected at the cervix with HPV-16, compared with 35 % (P=0.002) of women infected with HPV-16-related types (α9 HPV types), 14 % (P<0.0001) of women infected with HPV-16 non-related types and none of HPV-uninfected women. A significant correlation between HPV-16 infection and serum HPV-16-neutralizing antibodies was observed (r s=0.97; P=0.032). Cervical neutralizing antibodies were detected in 38 % of women with HPV-16 infection and in 17 % of women infected with the HPV-16-related type HPV-31. Cervical neutralizing antibodies correlated with HPV-16 infection (r s=0.95; P=0.08), but not with cervical disease. Serum and cervical HPV-16 antibody responses were not affected significantly by human immunodeficiency virus type 1 infection. In conclusion, serum and cervical HPV-16-neutralizing antibodies were found to correlate with HPV-16 infection, but not with cervical disease.

scholarly journals Characterization of two new monoclonal antibodies against human papillomavirus type 16 L1 protein

2014 ◽  
Vol 9 (1) ◽  
pp. 101 ◽  
Author(s):  
Yan Wang ◽  
Qinglong Shang ◽  
Weizhen Xu ◽  
Di Li ◽  
Hongxi Gu ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

scholarly journals Probing neutralizing-antibody responses against emerging measles viruses (MVs): immune selection of MV by H protein-specific antibodies?

2005 ◽  
Vol 86 (2) ◽  
pp. 365-374 ◽  
Author(s):  
Sabine Santibanez ◽  
Stefan Niewiesk ◽  
Alla Heider ◽  
Jürgen Schneider-Schaulies ◽  
Guy A. M. Berbers ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Neutralizing Capacity ◽  
Human Sera ◽  
H Protein ◽  
Neutralizing Epitopes ◽  
Selection Of

Measles virus (MV) infection and vaccination induce long-lasting immunity and neutralizing-antibody responses that are directed against the MV haemagglutinin (H) and the fusion (F) protein. A new MV genotype, D7, emerged recently in western Germany and rapidly replaced the long-term endemically circulating genotypes C2 and D6. Analysis of the H gene of C2, D6, D7 and vaccine viruses revealed uniform sequences for each genotype. Interestingly, a consistent exchange of seven distinct amino acids in the D7 H was observed when compared with residues shared between C2, D6 and vaccine viruses, and one exchange (D416→N) in the D7 H was associated with an additional N-linked glycosylation. In contrast, the F gene is highly conserved between MVs of these genotypes. To test whether the D7 H protein escapes from antibody responses that were raised against earlier circulating or vaccine viruses, the neutralizing capacity of mAbs recognizing seven distinct domains on the H of an Edmonston-related MV was compared. The mAbs revealed a selective and complete loss of two neutralizing epitopes on the D7 H when compared with C2, D6 and vaccine viruses. To assess whether these alterations of the D7 H affect the neutralizing capacity of polyclonal B-cell responses, genotype-specific antisera were produced in cotton rats. However, no significant genotype-dependent difference was found. Likewise, human sera obtained from vaccinees (n=7) and convalescents (n=6) did not distinguish between the MV genotypes. Although the hypothesis of selection of D7 viruses by pre-existing neutralizing antibodies is compatible with the differing pattern of neutralizing epitopes on the H protein, it was not confirmed by the results of MV neutralization with polyclonal sera.

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