Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.
Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs.
Understanding the transmission patterns of West Nile and St. Louis encephalitis viruses (family Flaviviridae, genus Flavivirus, WNV and SLEV) could result in an increased ability to predict transmission risk to humans. To examine transmission patterns between vector and host, we trapped mosquitoes in three Florida counties from June to November 2005 by using chicken-baited lard can mosquito traps. These traps were used to monitor for presence of WNV and SLEV in mosquitoes and subsequent transmission of these viruses to chickens. In total, 166,615 female mosquitoes were sorted into 4,009 pools based on species and bloodfed status, and they were tested for presence of WNV and SLEV. Sera from 209 chickens were tested for WNV and SLEV antibodies. We detected eight WNV-positive Culex nigripalpus Theobald mosquito pools; SLEV was not detected in any pools. Six positive pools were collected in August and September from Duval County, one pool in September from Manatee County, and one pool in November from Indian River County. Of the eight chickens potentially exposed to WNV, antibodies were detected in only one chicken, indicating a low rate of transmission relative to the observed mosquito infection rates. Low virus transmission rates relative to infection rates would suggest that using sentinel chicken seroconversion data as a means of arbovirus surveillance may underestimate the prevalence of WNV in the mosquito population. However, using mosquito infection rates may overestimate the risk of arboviral transmission. A variety of factors might account for the observed low level of transmission including a lack of viral dissemination in mosquito vectors.
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