Abstract. A candidate live-attenuated virus vaccine for protection against Venezuelan equine encephalitis (VEE) (designated V3526) was tested in mice to measure the magnitude, duration, and kinetics of virus replication in the blood and the central nervous system and its phenotypic stability after multiple passages in mice and cell culture. All results were compared to parallel experiments with parental virus and the existing VEE virus vaccine, TC-83. Maximum virus titers in the brains of V3526-inoculated mice were between 10-and 100-fold less than those observed in brains of mice inoculated intracranially (ic) with either the parental virus or TC-83. Neither V3526 nor TC-83 was lethal in BALB/c mice inoculated ic. However, mice inoculated with TC-83 developed acute symptoms lasting at least 14 days. In contrast, ic inoculation of TC-83 was uniformly lethal for C3H/HeN mice. V3526 was avirulent in both BALB/c and C3H/HeN mice after ic inoculation. The virulence characteristics of V3526 remained unchanged after five serial ic passages in mouse brains or after five cell culture passages. Finally, pathologic changes induced after ic inoculation of V3526 were consistently less severe and of shorter duration than those observed in TC-83-inoculated mice. Based on these results, V3526 is stable and appears to be significantly less neurovirulent in mice than TC-83.

Analysis of convalescent plasma derived from individuals has shown that IgG3 has the most important role in binding to SARS-CoV-2 antigens; however, this has not yet been confirmed in large studies, and the link between binding and neutralization has not been confirmed. By analyzing plasma pools consisting of 247–567 individual convalescent donors, we demonstrated the binding of IgG3 and IgM to Spike-1 protein and the receptor-binding domain correlates strongly with viral neutralization in vitro. Furthermore, despite accounting for only approximately 12% of total immunoglobulin mass, collectively IgG3 and IgM account for approximately 80% of the total neutralization. This may have important implications for the development of potent therapies for COVID-19, as it indicates that hyperimmune globulins or convalescent plasma donations with high IgG3 concentrations may be a highly efficacious therapy.

Background COVID‐19 convalescent plasma (CCP) was approved under emergency authorization to treat critically ill patients with COVID‐19 in the United States in 2020. We explored the demographics of donors contributing plasma for a hyperimmune, plasma‐derived therapy to evaluate factors that may be associated with anti‐SARS‐CoV‐2 antibody response variability and, subsequently, antibody titers. Study Design An electronic search of CCP donors was performed across 282 US plasma donation centers. Donations were screened for nucleocapsid protein‐binding‐IgG using the Abbott SARS‐CoV‐2 IgG assay. Results Overall, 52 240 donors donated 418 046 units of CCP. Donors were of various ethnicities: 43% Caucasian, 34% Hispanic, 17% African American, 2% Native American, 1% Asian, and 3% other. Females had higher initial mean anti‐SARS‐CoV‐2 antibody titers but an overall faster rate of decline ( P < .0001). Initial antibody titers increased with age: individuals aged 55 to 66 years had elevated anti‐SARS‐CoV‐2 titers for longer periods compared with other ages ( P = .0004). African American donors had the lowest initial antibody titers but a slower rate of decline ( P < .0001), while Caucasian ( P = .0088) and Hispanic ( P = .0193) groups had the fastest rates of decline. Most donor antibody levels decreased below the inclusion criteria (≥1.50) within 30 to 100 days of first donation, but donation frequency did not appear to be associated with rate of decline. Conclusion Several factors may be associated with anti‐SARS‐CoV‐2 antibody response including donor age and sex. Evaluating these factors during development of future hyperimmune globulin products may help generation of therapies with optimal efficacy.

Background Plasma-derived intravenous immunoglobulin (IVIg) products contain a dynamic spectrum of immunoglobulin (Ig) G reactivities reflective of the donor population from which they are derived. We sought to model the concentration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG which could be expected in future plasma pool and final-product batches of CSL Behring’s immunoglobulin product Privigen. Study design and methods Data was extracted from accessible databases, including the incidence of coronavirus disease 2019 and SARS-CoV-2 vaccination status, antibody titre in convalescent and vaccinated groups and antibody half-life. Together, these parameters were used to create an integrated mathematical model that could be used to predict anti-SARS-CoV-2 antibody levels in future IVIg preparations. Results We predict that anti-SARS-CoV-2 IgG concentration will peak in batches produced in mid-October 2021, containing levels in the vicinity of 190-fold that of the mean convalescent (unvaccinated) plasma concentration. An elevated concentration (approximately 35-fold convalescent plasma) is anticipated to be retained in batches produced well into 2022. Measurement of several Privigen batches using the Phadia™ EliA™ SARS-CoV-2-Sp1 IgG binding assay confirmed the early phase of this model. Conclusion The work presented in this paper may have important implications for physicians and patients who use Privigen for indicated diseases.

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