SARS-CoV-2 Convalescent Sera Binding and Neutralizing Antibody Concentrations Compared with COVID-19 Vaccine Efficacy Estimates Against Symptomatic Infection

Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, [~]88% of neutralizing and [~]63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; [~]30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19.

Calibration of Two Validated SARS-CoV-2 Pseudovirus Neutralization Assays for COVID-19 Vaccine Evaluation

Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States Government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organizations anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.

Cytoplasmic 5-Lipoxygenase Staining Is a Highly Sensitive Marker of Human Tumors of the Choroid Plexus.

OBJECTIVES: To determine the immunoreactivity status of 5-lipoxygenase (5-LO) in normal tissues, in tumors of the human choroid plexus, and in other brain tumors. METHODS: In total, 135 cases of various types of brain tumors were selected. Tissue samples were immunostained with a rabbit polyclonal anti-5-LO antibody. RESULTS: Nuclear reactivity was observed in most brain tumors, with most of the positive tumor cells exhibiting low-level reactivity. Cytoplasmic strong immunoreactivity for 5-LO (2+ or 3+) was only observed in 8.8% of astrocytic tumors, 0% of oligodendrogliomatous tumors, 5.6% of ependymal tumors, 0% of embryonal tumors, 3.1% of meningeal tumors, and 0% of metastatic lung adenocarcinomas. In contrast, cytoplasmic immunoreactivity for 5-LO was detected in all 27 cases of choroid plexus tumors. Twenty-five cases showed strong and diffuse cytoplasmic immunoreactivity. CONCLUSIONS: Our findings indicate that cytoplasmic 5-LO immunoreactivity is highly characteristic of human choroid plexus tumors but not other central nervous system tumor types. Cytoplasmic staining for 5-LO may prove to be a useful immunoreactive marker in the diagnosis of choroid plexus tumors.