Structure and neutralization mechanism of a human antibody targeting a complex Epitope on Zika virus.

We currently have an incomplete understanding of why only a fraction of human antibodies that bind to flaviviruses block infection of cells. Here we define the footprint of a strongly neutralizing human monoclonal antibody (mAb G9E) with Zika virus (ZIKV) by both X-ray crystallography and cryo-electron microscopy. Flavivirus envelope (E) glycoproteins are present as homodimers on the virion surface, and G9E bound to a quaternary structure epitope spanning both E protomers forming a homodimer. As G9E mainly neutralized ZIKV by blocking a step after viral attachment to cells, we tested if the neutralization mechanism of G9E was dependent on the mAb cross-linking E molecules and blocking low-pH triggered conformational changes required for viral membrane fusion. We introduced targeted mutations to the G9E paratope to create recombinant antibodies that bound to the ZIKV envelope without cross-linking E protomers. The G9E paratope mutants that bound to a restricted epitope on one protomer poorly neutralized ZIKV compared to the wild-type mAb, demonstrating that the neutralization mechanism depended on the ability of G9E to cross-link E proteins. In cell-free low pH triggered viral fusion assay, both wild-type G9E, and epitope restricted paratope mutant G9E bound to ZIKV but only the wild-type G9E blocked fusion. We propose that, beyond antibody binding strength, the ability of human antibodies to cross-link E-proteins is a critical determinant of flavivirus neutralization potency.

Changes in the Seroprevalence of Tick-Borne Rickettsia and Ehrlichia Among Soldiers-Fort Liberty, North Carolina, 1991-2019.

We obtained samples from the Department of Defense Serum Repository from soldiers who were stationed at Fort Liberty, North Carolina, between 1991 and 2019 to assess temporal trends in tick-borne rickettsiosis and ehrlichiosis. Serological evidence of infection was common, with nearly 1 in 5 (18.9%) demonstrating antibodies. We observed significant decreases in Rickettsia seroprevalence (adjusted odds ratio [aOR], 0.42 [95% CI, .27-.65], P = .0001) while over the same period Ehrlichia seroprevalence, albeit less common, nearly doubled (aOR, 3.61 [95% CI, 1.10-13.99], P = .048). The increase in Ehrlichia seroprevalence likely reflects increased transmission resulting from the expanding geographic range of the lone star tick.

Epidemiology and outcomes of hyphema: a single tertiary centre experience of 180 cases.

PURPOSE: To characterize the epidemiology and outcomes of hyphema. METHODS: Retrospective case series. Medical records from patients with traumatic and spontaneous hyphema seen at the Wilmer Eye Institute, Johns Hopkins, from 2011 through 2017 were evaluated. Aetiology, demographics, clinical characteristics, complications, management and outcomes were ascertained. Multivariable logistic regression was used to identify factors associated with elevated intraocular pressure (IOP), rebleeding and poor outcome (final visual acuity ≤ 20/40) in traumatic hyphema. A safe frequency of follow-up was retrospectively determined. RESULTS: Traumatic hyphema (n = 152) was more common in males (78%) and adults (55%), with sports/recreational activities being the most frequent cause (40%). Elevated IOP was the most common complication (39%). Rebleeding occurred in seven patients (5%) and was more likely with a higher IOP on presentation (OR:1.1; p = 0.004). Thirty-seven patients (24%) had a poor outcome, mostly due to traumatic sequelae such as cataract (32%) or posterior segment involvement (30%). A poor outcome was more likely with worse presenting visual acuity (OR: 9.1; p = 0.001), rebleeding (OR: 37.5; p = 0.035) and age > 60 years (OR: 16.0; p = 0.041). Spontaneous hyphema (n = 28) did not have a gender predominance and was more common in adults > 60 years (71%). The most common cause was iris neovascularization (61%). Complications and visual outcomes were worse compared with traumatic hyphema. CONCLUSIONS: Traumatic hyphema continues to be common in young males engaging in sports, necessitating increased awareness for preventive eyewear. Older age and rebleeding can lead to poor outcomes. Elevated IOP at presentation predisposes to rebleeding and warrants frequent follow-up. Otherwise, routine follow-up at days 1, 3, 5, 7 and 14 is sufficient for uncomplicated cases.