Related Experiment Videos
Monoclonal antibodies for dengue virus prM glycoprotein protect mice against lethal dengue infection
B M Kaufman1, P L Summers, D R Dubois
1Walter Reed Army Institute of Research, Washington, DC.
Abstract:
Five murine monoclonal antibodies (Mabs) reactive against the prM glycoproteins of DEN-3 and -4 were used to passively protect mice in vivo against lethal challenge with homologous and heterologous dengue virus serotypes. Four of the 5 prM-reactive monoclonals cross-protected mice against heterologous challenge, whereas 1 protected against challenge with only the homologous serotype. Although in vitro binding to virions was readily demonstrated, only 2 of the prM Mabs had detectable neutralizing activity. The neutralizing activity could not be enhanced by anti-mouse immunoglobulin or complement. However, 4 of the 5 prM Mabs fixed complement. This is the first report of prM-specific Mabs that are protective in mice.
Insights
New monoclonal antibodies (Mabs) targeting dengue virus prM glycoproteins show protective capabilities in mice. This research highlights prM-specific Mabs as a potential strategy for dengue fever prevention.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Dengue virus (DENV) poses a significant global health threat, necessitating novel therapeutic strategies.
- Monoclonal antibodies (Mabs) are being explored for their potential in preventing and treating DENV infections.
- The prM glycoprotein of DENV is a potential target for antibody-based interventions.
Purpose of the Study:
- To investigate the efficacy of murine monoclonal antibodies (Mabs) targeting the DENV prM glycoprotein in protecting mice against lethal DENV challenge.
- To characterize the in vitro and in vivo properties of prM-specific Mabs, including neutralization and complement fixation.
Main Methods:
- Generation and characterization of five murine monoclonal antibodies (Mabs) reactive against DENV-3 and DENV-4 prM glycoproteins.
- In vivo passive protection assays using Mabs to protect mice against lethal homologous and heterologous DENV challenge.
- In vitro assessment of Mab binding to DENV virions, viral neutralization activity, and complement fixation.
Main Results:
- Four out of five prM-specific Mabs conferred cross-protection against heterologous DENV serotypes in mice.
- One Mab demonstrated protection exclusively against the homologous DENV serotype.
- While most Mabs bound to virions, only two exhibited detectable in vitro neutralizing activity.
- Four of the five prM Mabs were found to fix complement.
Conclusions:
- This study reports the first instance of prM-specific monoclonal antibodies demonstrating protective effects in a murine model of dengue virus infection.
- prM-specific Mabs, particularly those capable of cross-protection and complement fixation, represent a promising avenue for developing dengue virus therapeutics.
- Further research into the mechanisms of protection mediated by prM-specific Mabs is warranted.