| dc.description.abstract | During a field expedition with the Centers for Disease Control and Prevention to South Sudan and Uganda, a wildlife researcher who had been collecting bat and rodent samples became ill and was hospitalized with a severe acute febrile disease shortly after the group returned to the United States of America. The causative agent for the researcher’s near-fatal disease was determined to be a novel paramyxovirus in subfamily Rubulavirinae, whose genome was found in the researcher’s blood. This virus was named Sosuga virus (SOSV) and was later identified in Egyptian rousette bat samples—the likely reservoir host of the virus. Using peripheral blood mononuclear cells donated by the researcher 5 years post-infection, a total of 24 SOSV-reactive monoclonal antibodies were isolated. Six of the mAbs reacted to the SOSV hemagglutinin-neuraminidase (HN) glycoprotein and 18 to the SOSV fusion (F) glycoprotein. Using ELISA assays, it was determined that the anti-HN mAbs fall into 4 competition-binding groups all recognizing the globular head domain of the glycoprotein. Due to the conformational instability of the SOSV F protein, the anti-F mAb panel could be first divided into groups recognizing specific conformations: prefusion-specific (9 mAbs), pre- and & postfusion specific (8 mAbs), and postfusion-specific (1 mAb). Conformation-specificity and competition-binding together indicate there are 8 competition-binding groups recognized by the panel of anti-F rmAbs. Neutralization assays conducted at biosafety level 3 found that the anti-HN rmAbs were ultra-potent, with several having 50% inhibitory concentrations (IC50) below 2 ng/mL; rSOSV-24 is the most potent anti-HN mAb. Of the anti-F rmAbs, the prefusion-specific mAbs tended to be more potently neutralizing, with rSOSV-10 being the most potent anti-F mAb. Only the postfusion-specific rmAb could not neutralize SOSV. While some of the anti-F antibodies had cross-reactivity to Tuhoko virus 3, a closely related pararubulavirus to SOSV, a single antibody (rSOSV-77) showed cross-reactivity to the human mumps virus (genotype G), which is in the more distant Orthorubulavirus genus. The antibodies discovered during this project represent the first human mAbs against any virus within Rubulavirinae and are some of the mostly potently neutralizing antibodies discovered in the field of antiviral antibody studies. | |
