Non-neutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis

Schmaljohn, A. L.; Johnson, E. D.; Dalrymple, Joel M.; Cole, Gerald A.

doi:10.1038/297070a0

Cited by 214 publications

(137 citation statements)

References 12 publications

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“…Other investigators have suggested that some non-neutralizing antibodies afford protection by sensitizing infected cells to complement-mediated cytolysis (Schmaljohn et al, 1982;Boere et al, 1985). Results obtained with antibodies to the yellow fever virus NS 1 glycoprotein, which is expressed on the surface of infected cells, were consistent with this model (Schlesinger et al, 1985).…”

Section: Short Communicationsupporting

confidence: 76%

Synergistic Interactions of Anti-NS1 Monoclonal Antibodies Protect Passively Immunized Mice from Lethal Challenge with Dengue 2 Virus

Henchal

Schlesinger

1988

Journal of General Virology

197

145

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Section: Short Communicationsupporting

confidence: 76%

Synergistic Interactions of Anti-NS1 Monoclonal Antibodies Protect Passively Immunized Mice from Lethal Challenge with Dengue 2 Virus

Henchal

Schlesinger

1988

Journal of General Virology

197

145

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“…The UM 4.2 antibodies which do not neutralize in vitro are nevertheless able to protect mice in vivo. A similar phenomenon was reported by Schmaljohn et al (1982) for non-neutralizing MA directed against the closely related Sindbis virus and by Balachandran et al (1982) for herpes simplex virus type 2. The latter authors explain the in vivo protection by suggesting a mechanism of antibody-dependent cell-mediated cytolysis (ADCC).…”

Section: Neutralizing and Non-neutralizing Monoclonal Antibodies To Tsupporting

confidence: 50%

Neutralizing and Non-neutralizing Monoclonal Antibodies to the E2 Glycoprotein of Semliki Forest Virus Can Protect Mice from Lethal Encephalitis

Boere

Benaissa-Trouw

Harmsen

et al. 1983

Journal of General Virology

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SUMMARYTwo monoclonal antibodies (UM 4.2 and UM 5.1) directed against the glycoprotein E2 of Semliki Forest virus (SFV) are described; both belong to the IgG2a isotype but are of different idiotype. Analysis employing isoelectric focusing resulted in different focusing patterns for both monoclonals (UM 4.2, pI 8; UM 5.1, pI 7.2). They further differed in their ability to neutralize virus. The UM 4.2 antibodies were inactive in neutralization, while the UM 5.1 antibodies exceeded conventional mouse hyperimmune serum in this respect. Both monoclonal antibodies, however, were able to protect mice passively from a lethal infection with SFV. Based on the amount of protein, the UM 5.1 antibodies were 100-fold more effective than the UM 4.2 antibodies in mouse protection tests.Immunization of mice with an avirulent strain of Semliki Forest virus (SFV) results in production of a heterogeneous population of antibodies which are able to interfere with different viral activities like infectivity and haemagglutination (Dalrymple et al., 1976; Helenius et al., 1976). For an analysis of the role played by the individual membrane glycoproteins El, E2 and E 3 of SFV (Garoffet al., 1974), monospecific antibodies are required. We produced a panel of monoclonal antibodies (MA) directed against the glycoproteins E1 and E2. Two MA specific for the E2 glycoprotein but differing in biological properties are studied in this paper.BALB/c mice were immunized with the avirulent SFV strain MRS MP 192/7 and spleen ceils were subsequently fused with P3-NS 1-1Ag4-1 (NS 1) myeloma cells, using the method described by Fazekas de St. Groth & Scheidegger (1980). Hybrids were selected in hypoxanthineaminopterin-thymidine medium (Littlefield, 1964) and antibody-producing clones by plaque titration and enzyme-linked immunosorbent assay (ELISA). Plaque titration and the plaque reduction test (PRT) have been described previously (Kraaijeveld et al., 1979b). ELISA was performed in Terasaki plates (Falcon Plastics) which had been coated with 10 ~tl amounts per well of 0-3 to 0-5 ~tg of purified inactivated SFV in 0.1 M-carbonate-bicarbonate buffer pH 9.6. Samples of hybridoma culture fluid (5 ~tl) were screened for anti-SFV antibody using goat antimouse IgG or IgM antibodies conjugated with alkaline phosphatase (Tago, Burlingame, Ca., U.S.A.). The substrate disodium p-nitrophenyl phosphate (Sigma) was added and the test was scored visually after 10 min. Positive cultures were subcloned by limiting dilution and tested again for anti-SFV activity. Positive clones were injected into pristane-primed female BALB/c mice (0.5 ml pristane intraperitoneally 1 to 2 weeks before injection of cells) at a dose of 1.0 × 106 to 5-0 x 106 cells/mouse. The antibody specificity in the resulting ascitic fluid was identified by immunoblotting (Fig. 1 a). Two clones, UM 4.2 and UM 5.1, showed specificity for the E2 glycoprotein ofSFV. Hyperimmune mouse serum served as a control and reacted with both glycoproteins E1 and E2 as expected.Antibody subclasses were determined by...

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“…Passive administration of non-neutralizing anti-E ld monoclonal antibodies can prevent lethal encephalitis in mice (Mathews & Roehrig, 1982;Schmaljohn et al, 1982;Hunt & Roehrig, 1985). These results indicate that expression of VEE epitopes E1 b and E1 d in addition to E2 epitopes by a genetically engineered vaccine may be a more effective immunogen than recombinant vaccines that express E2 antigenic determinants alone.…”

Section: Discussionmentioning

confidence: 75%

Recombinant Vaccinia/Venezuelan Equine Encephalitis (VEE) Virus Expresses VEE Structural Proteins

Kinney

Esposito

Johnson

et al. 1988

Journal of General Virology

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SUMMARYcDNA molecules encoding the structural proteins of the virulent Trinidad donkey and the TC-83 vaccine strains of Venezuelan equine encephalitis (VEE) virus were inserted under control of the vaccinia virus 7.5K promoter into the thymidine kinase gene of vaccinia virus. Synthesis of the capsid protein and glycoproteins E2 and E1 of VEE virus was demonstrated by immunoblotting of lysates of CV-1 cells infected with recombinant vaccinia/VEE viruses. VEE glycoproteins were detected in recombinant virus-infected cells by fluorescent antibody (FA) analysis performed with a panel of VEE-specific monoclonal antibodies. Seven E2-specific epitopes and two of four Elspecific epitopes were demonstrated by FA.

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Non-neutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis

Cited by 214 publications

References 12 publications

Synergistic Interactions of Anti-NS1 Monoclonal Antibodies Protect Passively Immunized Mice from Lethal Challenge with Dengue 2 Virus

Synergistic Interactions of Anti-NS1 Monoclonal Antibodies Protect Passively Immunized Mice from Lethal Challenge with Dengue 2 Virus

Neutralizing and Non-neutralizing Monoclonal Antibodies to the E2 Glycoprotein of Semliki Forest Virus Can Protect Mice from Lethal Encephalitis

Recombinant Vaccinia/Venezuelan Equine Encephalitis (VEE) Virus Expresses VEE Structural Proteins

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