Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential

Logu, Alessandro De; Williamson, R. Anthony; Rozenshteyn, Roman; Ramiro-Ibañez, F.; Simpson, Cindy D.; Burton, Dennis R.; Sanna, Pietro Paolo

doi:10.1128/jcm.36.11.3198-3204.1998

Cited by 30 publications

(22 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PEI assay. The postentry assay was adapted from previous studies (20,38) as previously described (18,19). Confluent monolayers of Vero E6 cells were infected with 100 PFU of virus.…”

Section: Methodsmentioning

confidence: 99%

Cell-to-Cell Spread Blocking Activity Is Extremely Limited in the Sera of Herpes Simplex Virus 1 (HSV-1)- and HSV-2-Infected Subjects

Criscuolo

Castelli

Diotti

et al. 2019

J Virol

View full text Add to dashboard Cite

Herpes simplex virus 1 (HSV-1) and HSV-2 can evade serum antibodymediated neutralization through cell-to-cell transmission mechanisms, which represent one of the central steps in disease reactivation. To address the role of humoral immunity in controlling HSV-1 and HSV-2 replication, we analyzed serum samples from 44 HSV-1 and HSV-2 seropositive subjects by evaluating (i) their efficiency in binding both the purified viral particles and recombinant gD and gB viral glycoproteins, (ii) their neutralizing activity, and (iii) their capacity to inhibit the cell-to-cell virus passage in vitro. All of the sera were capable of binding gD, gB, and whole virions, and all sera significantly neutralized cell-free virus. However, neither whole sera nor purified serum IgG fraction was able to inhibit significantly cell-to-cell virus spreading in in vitro post-virus-entry infectious assays. Conversely, when spiked with an already described anti-gD human monoclonal neutralizing antibody capable of inhibiting HSV-1 and -2 cell-to-cell transmission, each serum boosted both its neutralizing and post-virus-entry inhibitory activity, with no interference exerted by serum antibody subpopulations. IMPORTANCE Despite its importance in the physiopathology of HSV-1 and -2 infections, the cell-to-cell spreading mechanism is still poorly understood. The data shown here suggest that infection-elicited neutralizing antibodies capable of inhibiting cell-to-cell virus spread can be underrepresented in most infected subjects. These observations can be of great help in better understanding the role of humoral immunity in controlling virus reactivation and in the perspective of developing novel therapeutic strategies, studying novel correlates of protection, and designing effective vaccines.

show abstract

“…PEI assay. The postentry assay was adapted from previous studies (20,38) as previously described (18,19). Confluent monolayers of Vero E6 cells were infected with 100 PFU of virus.…”

Section: Methodsmentioning

confidence: 99%

Cell-to-Cell Spread Blocking Activity Is Extremely Limited in the Sera of Herpes Simplex Virus 1 (HSV-1)- and HSV-2-Infected Subjects

Criscuolo

Castelli

Diotti

et al. 2019

J Virol

View full text Add to dashboard Cite

show abstract

“…To create a more humanized form of 2A10G6, the variable regions in 6D8 were replaced with the variable regions from 2A10G6 (referred to as chimeric 2A10G6 or c2A10G6). Lastly, we also produced the mAb HSV8, a human-derived antibody which neutralizes herpes simplex virus (HSV) in mice and traps HSV in human cervicovaginal mucus (Zeitlin et al, 1996;De Logu et al, 1998;Schroeder et al, 2018). Optimized BeYDV vectors containing the plant codon-optimized c2A10G6, 6D8, and HSV8 heavy and light chain coding sequences were agroinfiltrated into glycoengineered N. benthamiana that produces highly homogenous mammalianlike glycans (Strasser et al, 2008;Montero-Morales and Steinkellner, 2018).…”

Section: Expression Of Mabs Using Optimized Plant Expression Vectorsmentioning

confidence: 99%

High Level Production of Monoclonal Antibodies Using an Optimized Plant Expression System

Diamos¹,

Hunter²,

Pardhe³

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Biopharmaceuticals are a large and fast-growing sector of the total pharmaceutical market with antibody-based therapeutics accounting for over 100 billion USD in sales yearly. Mammalian cells are traditionally used for monoclonal antibody production, however plant-based expression systems have significant advantages. In this work, we showcase recent advances made in plant transient expression systems using optimized geminiviral vectors that can efficiently produce heteromultimeric proteins. Two, three, or four fluorescent proteins were coexpressed simultaneously, reaching high yields of 3-5 g/kg leaf fresh weight or ∼50% total soluble protein. As a proof-of-concept for this system, various antibodies were produced using the optimized vectors with special focus given to the creation and production of a chimeric broadly neutralizing anti-flavivirus antibody. The variable regions of this murine antibody, 2A10G6, were codon optimized and fused to a human IgG1. Analysis of the chimeric antibody showed that it was efficiently expressed in plants at 1.5 g of antibody/kilogram of leaf tissue, can be purified to near homogeneity by a simple one-step purification process, retains its ability to recognize the Zika virus envelope protein, and potently neutralizes Zika virus. Two other monoclonal antibodies were produced at similar levels (1.2-1.4 g/kg). This technology will be a versatile tool for the production of a wide spectrum of pharmaceutical multi-protein complexes in a fast, powerful, and cost-effective way.

show abstract

“…The human recombinant monoclonal anti-HSV-1 antibody (HSV8) used in this study was previously described (3,38,46). This type-common antibody recognizes the highly conserved and protective antigenic site Ib (8,12). It efficiently neutralizes both laboratory strains and low-passage clinical isolates of both HSV serotypes, inhibits cell fusion by a syncytium-inducing HSV-1 strain, and inhibits cell-to-cell spread of HSV-1 and -2 in inhibition-of-plaque development assays (3,8).…”

Section: Methodsmentioning

confidence: 99%

“…This type-common antibody recognizes the highly conserved and protective antigenic site Ib (8,12). It efficiently neutralizes both laboratory strains and low-passage clinical isolates of both HSV serotypes, inhibits cell fusion by a syncytium-inducing HSV-1 strain, and inhibits cell-to-cell spread of HSV-1 and -2 in inhibition-of-plaque development assays (3,8). It also proved to be protective against viral challenge in nude mice (38,39).…”

Section: Methodsmentioning

confidence: 99%

Neutralizing Antibodies Inhibit Axonal Spread of Herpes Simplex Virus Type 1 to Epidermal Cells In Vitro

Mikloška

Sanna

Cunningham

1999

J Virol

View full text Add to dashboard Cite

The ability of antibodies to interfere with anterograde transmission of herpes simplex virus (HSV) from neuronal axons to the epidermis was investigated in an in vitro model consisting of human fetal dorsal root ganglia innervating autologous skin explants in a dual-chamber tissue culture system. The number and size of viral cytopathic plaques in epidermal cells after axonal transmission from HSV type 1 (HSV-1)-infected dorsal root ganglionic neurons were significantly reduced by addition to the outer chamber of neutralizing polyclonal human sera to HSV-1, of a human recombinant monoclonal group Ib antibody to glycoprotein D (gD), and of rabbit sera to HSV-1 gB and gD but not by rabbit anti-gE or anti-gG. A similar pattern of inhibition of direct infection of epidermal cells by these antibodies was observed. High concentrations of the monoclonal anti-gD reduced transmission by 90%. Rabbit anti-gB was not taken up into neurons, and human anti-gD did not influence spread of HSV in the dorsal root ganglia or axonal transport of HSV antigens when applied to individual dissociated neurons. These results suggest that anti-gD and -gB antibodies interfere with axonal spread of HSV-1, possibly by neutralizing HSV during transmission across an intercellular gap between axonal termini and epidermal cells, and thus contribute to control of HSV spread and shedding. Therefore, selected human monoclonal antibodies to protective epitopes might even be effective in preventing epidermis-to-neuron transmission during primary HSV infection, especially neonatal infection.

show abstract

Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential

Cited by 30 publications

References 43 publications

Cell-to-Cell Spread Blocking Activity Is Extremely Limited in the Sera of Herpes Simplex Virus 1 (HSV-1)- and HSV-2-Infected Subjects

Cell-to-Cell Spread Blocking Activity Is Extremely Limited in the Sera of Herpes Simplex Virus 1 (HSV-1)- and HSV-2-Infected Subjects

High Level Production of Monoclonal Antibodies Using an Optimized Plant Expression System

Neutralizing Antibodies Inhibit Axonal Spread of Herpes Simplex Virus Type 1 to Epidermal Cells In Vitro

Contact Info

Product

Resources

About