The effect of SARS-CoV-2 seropositivity on the immune response to mRNA-based SARS-CoV-2 vaccines has not been well-described. Here we report longitudinal SARS-CoV-2-specific antibody responses pre- and post-vaccination among a cohort of healthcare personnel, with and without prior infection, from a large academic medical center. Our results provide preliminary evidence that prior SARS-CoV-2 infection may prime the response to the first mRNA-based SARS-CoV-2 vaccine dose. These findings could have significant impact on the allocation of mRNA-based vaccines and support the need for future research into the effect of prior infection on magnitude and durability of vaccination response.

Highlights d The identified human type-specific mAbs target diverse antigenic sites on DENV3 E d Chimeric DENV viruses encode functional DENV3 neutralizing epitopes d Functional neutralizing epitopes can be rapidly mapped by using chimeric DENV viruses d Selected mAbs potently neutralize multiple genotype strains of DENV3 viruses

Background Health care personnel (HCP) are at high risk for exposure to the SARS-CoV-2 virus. While personal protective equipment (PPE) may mitigate this risk, prospective data collection on its use and other risk factors for seroconversion in this population is needed. Objective The primary objectives of this study are to (1) determine the incidence of, and risk factors for, SARS-CoV-2 infection among HCP at a tertiary care medical center and (2) actively monitor PPE use, interactions between study participants via electronic sensors, secondary cases in households, and participant mental health and well-being. Methods To achieve these objectives, we designed a prospective, observational study of SARS-CoV-2 infection among HCP and their household contacts at an academic tertiary care medical center in North Carolina, USA. Enrolled HCP completed frequent surveys on symptoms and work activities and provided serum and nasal samples for SARS-CoV-2 testing every 2 weeks. Additionally, interactions between participants and their movement within the clinical environment were captured with a smartphone app and Bluetooth sensors. Finally, a subset of participants’ households was randomly selected every 2 weeks for further investigation, and enrolled households provided serum and nasal samples via at-home collection kits. Results As of December 31, 2020, 211 HCP and 53 household participants have been enrolled. Recruitment and follow-up are ongoing and expected to continue through September 2021. Conclusions Much remains to be learned regarding the risk of SARS-CoV-2 infection among HCP and their household contacts. Through the use of a multifaceted prospective study design and a well-characterized cohort, we will collect critical information regarding SARS-CoV-2 transmission risks in the health care setting and its linkage to the community. International Registered Report Identifier (IRRID) DERR1-10.2196/25410

Background Diagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment. Methology/principle findings Here we describe proof of concept for a novel urine diagnostics for TE using Poly-N-isoproplyacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic. Conclusion/significances Our results demonstrate nanoparticle technology’s potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.

The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others are implicated in enhanced viral replication and more severe disease. Current dengue tetravalent vaccines contain four live attenuated serotypes formulated to theoretically induce balanced protective immunity. Among the number of vaccine candidates in clinical trials, only Dengvaxia is licensed for use in DENV seropositive individuals. To simplify live-virus vaccine design, we identify co-evolutionary constraints inherent in flavivirus virion assembly and design chimeric viruses to replace domain II (EDII) of the DENV2 envelope (E) glycoprotein with EDII from DENV4. The chimeric DENV2/4EDII virus replicates efficiently in vitro and in vivo. In male macaques, a single inoculation of DENV2/4EDII induces type-specific neutralizing antibodies to both DENV2 and DENV4, thereby providing a strategy to simplify DENV vaccine design by utilizing a single bivalent E glycoprotein immunogen for two DENV serotypes.