Abstract
Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection.
Highlights
Rift Valley fever virus (RVFV) belongs to the family Phenuiviridae, genus Phlebovirus and contains a single stranded tripartite genome of negative polarity
Pathological and molecular analysis clearly indicated a strong reduction of virus replication in target tissues of treated mice. These results identified two monoclonal antibodies with strong antiviral effects against Rift Valley fever infection, which are promising candidates for therapeutic interventions against RVFV
In vitro characterization of mAbs Gn3 and Gn32. The binding of both monoclonal antibodies Gn3 and Gn32 to recombinant RVFV Gn ectodomain was assessed in ELISA yielding EC50 values of about 1.29 μg/ml and 0.38 μg/ml (Fig 1)
Summary
Rift Valley fever virus (RVFV) belongs to the family Phenuiviridae, genus Phlebovirus and contains a single stranded tripartite genome of negative polarity. It consists of three segments that code for nucleocapsid protein (S-segment), two glycoproteins Gn, Gc (M-segment) and a RNA dependent RNA polymerase (L-segment). Two non-structural proteins are encoded by the S-segment (NSs) and M-segment (NSm), respectively [1]. The virus emerged during the 1970ths and 1980ths throughout Africa and entered the Arabian Peninsula in 2000 [4]. Main focus with re-occurrent epidemics are Sub-Saharan countries (e.g. Mauritania), South-Africa, Tanzania, Kenya and Egypt [4]. Based on this emergence and due to numerous susceptible mosquito species that are found in Europe, there is a significant risk for introduction and subsequent dissemination of RVFV in Europe [5]
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