Monoclonal Antibodies against Dengue 2 Virus E-Glycoprotein Protect Mice against Lethal Dengue Infection

Abstract

A panel of 11 murine monoclonal antibodies directed against dengue type 2 was evaluated for antigen specificity by dot immunobinding assay and Western blot analysis and for in vitro and in vivo biological activities. Nine of the 11 monoclonal antibodies reacted with viral E-glycoprotein based on the Western blot analysis; one reacted with a 36 Kd protein present in dengue-infected C6/36 mosquito cells. The nine E-glycoprotein-reactive monoclonal antibodies also neutralized dengue 2 virus in a plaque reduction assay. Of the neutralizing monoclonal antibodies, five passively protected mice in vivo against lethal intracerebral dengue 2 challenge. The protective monoclonal antibodies were directed against viral determinants that fell into at least three spatially separate families of epitopes on E-glycoprotein, the antigenicities of which were preserved after heat/detergent denaturation.

Characterization of antibody responses to combinations of a dengue-2 DNA and dengue-2 recombinant subunit vaccine.

“…We have previously shown that the recombinant vaccine contains epitopes reactive with DEN-2 type-specific neutralizing monoclonal antibodies 3H5 and 6B6 and several other DEN-2-specific, neutralizing, monoclonal antibodies have also been mapped to the B domain of the DEN-2 virus envelope protein. [22][23][24]26 It is conceivable that the amount of protein produced by the plasmid DNA in the cell may be too low for optimal CD4 ϩ T cell stimulation and subsequent B-cell proliferation and differentiation. The advantage of DNA vaccines is thought to reside in their ability to express foreign antigen inside the cell and access the endogenous pathway, leading to presentation by class I major histocompatibility antigens (MHC I).…”

“…Some infected people maintain detectable levels of neutralizing antibody to the homologous serotype for at least 40 years, and the presence of neutralizing antibody is thought to correlate with protection. 13,21,22 Our previous studies have demonstrated that a recombinant fusion protein containing 103 amino acids of the B domain of the DEN-2 envelope (E) protein fused to the maltose-binding protein (MBP) of Escherichia coli, and a DEN-2 DNA vaccine containing the premembrane (prM) and E genes were both immunogenic in mice and induced anti-DEN neutralizing antibody. 25,26 However, levels of neutralizing antibodies waned over time with both vaccine preparations.…”

Dengue 2 Virus Envelope Protein Expressed by a Recombinant Vaccinia Virus Fails to Protect Monkeys against Dengue

“…Plasma from each animal was tested daily for viraemia and for antibody response by ELISA (Kaufman et at., 1987) and NT assays (Russell et al, 1967).…”

Short report: Antibody responses of mice immunized with a tetravalent dengue recombinant protein subunit vaccine.

“…Neutralizing antibody is thought to be an important component of protective immunity on the basis of studies of infants born to dengue-immune mothers as well as on the basis of passive antibody transfer studies in animals. 17,18 However, to date, only a few studies have been published that discuss the use of bivalent vaccines, and to our knowledge, no detailed studies about trivalent or tetravalent dengue vaccines have been published.…”