scholarly journals Restoration of Complement-Enhanced Neutralization of Vaccinia Virus Virions by Novel Monoclonal Antibodies Raised against the Vaccinia Virus Complement Control Protein

2003 ◽  
Vol 77 (15) ◽  
pp. 8256-8262 ◽  
Author(s):  
Stuart N. Isaacs ◽  
Emelia Argyropoulos ◽  
Georgia Sfyroera ◽  
Shamim Mohammad ◽  
John D. Lambris
Keyword(s):  
Monoclonal Antibodies ◽  
Vaccinia Virus ◽  
Neutralization Assay ◽  
Smallpox Vaccination ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Activity ◽  
Western Blots ◽  
Complement Control Protein ◽  
Novel Approach ◽  
Control Protein

ABSTRACT The vaccinia virus complement control protein (VCP) is secreted by infected cells and has been shown to inhibit complement activation through interactions with C3b/C4b. It contains four short consensus repeat (SCR) domains. It has been suggested that all four SCRs are required for VCP's activity. To elucidate which SCR domains are involved in abolishing complement-enhanced neutralization of vaccinia virus virions, we generated and characterized a panel of mouse monoclonal antibodies (MAbs) raised against VCP. Ten MAbs were isolated and all recognized VCP on Western blots under reducing conditions as well as native-bound VCP in a sandwich enzyme-linked immunosorbent assay. Three of the 10 MAbs (2E5, 3D1, and 3F11) inhibited VCP's abolition of complement-enhanced neutralization of vaccinia virus virions. These MAbs blocked the interaction of VCP with C3b/C4b. The seven remaining MAbs did not alter VCP function in the complement neutralization assay and recognized VCP bound to C3b/C4b. To understand MAb specificity and mode of interaction with VCP, we mapped the MAb binding regions on VCP. The seven nonblocking MAbs all bound to the first SCR of VCP. One of the blocking MAbs recognized SCR 2 while the other two recognized either SCR 4 or the junction between SCRs 3 and 4, indicating that structural elements involved in the interaction of VCP with C3b/C4b are located within SCR domains 2 and 3 and 4. These anti-VCP MAbs may have clinical significance as therapeutic inhibitors of VCP's complement control activity and may also offer a novel approach to managing vaccinia virus vaccine complications that occur from smallpox vaccination.

scholarly journals Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity

Vaccine ◽  
2011 ◽  
Vol 29 (43) ◽  
pp. 7435-7443 ◽  
Author(s):  
John Bernet ◽  
Muzammil Ahmad ◽  
Jayati Mullick ◽  
Yogesh Panse ◽  
Akhilesh K. Singh ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Complement Control Protein ◽  
Control Protein

A Novel Approach for the Production of Monoclonal Antibodies Using Infectious Vaccinia Virus Recombinants

Hybridoma ◽  
1987 ◽  
Vol 6 (4) ◽  
pp. 329-335 ◽  
Author(s):  
TILAHUN YILMA ◽  
SANDRA S. RISTOW ◽  
BERNARD MOSS ◽  
LESLIE JONES
Keyword(s):  
Monoclonal Antibodies ◽  
Vaccinia Virus ◽  
Novel Approach

scholarly journals Persisting Humoral Antiviral Immunity within the Japanese Population after the Discontinuation in 1976 of Routine Smallpox Vaccinations

2005 ◽  
Vol 12 (4) ◽  
pp. 520-524 ◽  
Author(s):  
Shuji Hatakeyama ◽  
Kyoji Moriya ◽  
Masayuki Saijo ◽  
Yuji Morisawa ◽  
Ichiro Kurane ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Japanese Population ◽  
Neutralizing Antibodies ◽  
Antiviral Immunity ◽  
Smallpox Vaccination ◽  
Considerable Proportion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Immunoglobulin ◽  
Specific Igg ◽  
Induced Immunity

ABSTRACT Concerns have arisen recently about the possible use of smallpox for a bioterrorism attack. Routine smallpox vaccination was discontinued in Japan in 1976; however, it is uncertain exactly how long vaccination-induced immunity lasts. We sought to evaluate the seroprevalence and intensity of anti-smallpox immunity among representatives of the present Japanese population. The subjects included 876 individuals who were born between 1937 and 1982. Vaccinia virus-specific immunoglobulin G (IgG) levels were measured by enzyme-linked immunosorbent assay (ELISA), and 152 of 876 samples were also tested for the presence of neutralizing antibodies. Of the subjects who were born before 1962, between 1962 and 1968, and between 1969 and 1975, 98.6, 98.6, and 66.0%, respectively, still retained the vaccinia virus-specific IgG with ELISA values for optical density at 405 nm (OD405) of ≥0.10. The corresponding figures for retained IgGs with OD405 values of ≥0.30 were 91.0, 90.3, and 58.2%, respectively. Neutralizing antibodies were also maintained. The sera with OD405 values of ≥0.30 showed 89% sensitivity and a 93% positive predictive value for detection of neutralizing antibodies (≥4). Thus, approximately 80% of persons born before 1969 and 50% of those born between 1969 and 1975 were also found to have maintained neutralizing antibodies against smallpox. A considerable proportion of the previous vaccinated individuals still retain significant levels of antiviral immunity. This long-lasting immunity may provide some protective benefits in the case of reemergence of smallpox, and the disease may not spread as widely and fatally as generally expected.

scholarly journals Smallpox vaccines induce antibodies to the immunomodulatory, secreted vaccinia virus complement control protein

2009 ◽  
Vol 90 (11) ◽  
pp. 2604-2608 ◽  
Author(s):  
Joan E. Adamo ◽  
Clement A. Meseda ◽  
Jerry P. Weir ◽  
Michael J. Merchlinsky
Keyword(s):  
Vaccinia Virus ◽  
Humoral Response ◽  
Viral Proteins ◽  
Secreted Proteins ◽  
Complement Protein ◽  
Lethal Challenge ◽  
Complement Control Protein ◽  
Infected Cells ◽  
Control Protein ◽  
Primary Band

Vaccination with Dryvax elicits a broad humoral response against many viral proteins. Human vaccinia immune globulin was used to screen the secreted proteins from cells infected with Dryvax or the candidate smallpox vaccine LC16m8 to determine whether the protective humoral response included antibodies against secreted viral proteins. Many proteins were detected, with the primary band corresponding to a band of 28 or 30 kDa in cells infected with Dryvax or LC16m8, respectively. This was identified as the vaccinia virus complement protein (VCP), which migrated more slowly in LC16m8-infected cells due to post-translational glycosylation. Vaccinia virus deleted in VCP, vVCPko, protected mice from a lethal intranasal challenge of vaccinia Western Reserve strain. Mice vaccinated with purified VCP demonstrated a strong humoral response, but were not protected against a moderate lethal challenge of vaccinia virus, suggesting that the humoral response against VCP is not critical for protection.

Vaccinia virus complement control protein ameliorates hyperacute xenorejection by inhibiting xenoantibody binding

2002 ◽  
Vol 34 (8) ◽  
pp. 3277-3281 ◽  
Author(s):  
J.B Anderson ◽  
S.A Smith ◽  
R van Wijk ◽  
S Chien ◽  
G.J Kotwal
Keyword(s):  
Vaccinia Virus ◽  
Complement Control Protein ◽  
Control Protein
Sign in / Sign up

Export Citation Format

Share Document