A human monoclonal antibody combination rescues nonhuman primates from advanced disease caused by the major lineages of Lassa virus.

There are no approved treatments for Lassa fever (LF), which is responsible for thousands of deaths each year in West Africa. A major challenge in developing effective medical countermeasures against LF is the high diversity of circulating Lassa virus (LASV) strains with four recognized lineages and four proposed lineages. The recent resurgence of LASV in Nigeria caused by genetically distinct strains underscores this concern. Two LASV lineages (II and III) are dominant in Nigeria. Here, we show that combinations of two or three pan-lineage neutralizing human monoclonal antibodies (8.9F, 12.1F, 37.D) known as Arevirumab-2 or Arevirumab-3 can protect up to 100% of cynomolgus macaques against challenge with both lineage II and III LASV isolates when treatment is initiated at advanced stages of disease on day 8 after LASV exposure. This work demonstrates that it may be possible to develop postexposure interventions that can broadly protect against most strains of LASV.

Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans.

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

Systematic Review and Principal Components Analysis of the Immunogenicity of Adalimumab.

BACKGROUND: The reported immunogenicity rates of adalimumab differ significantly between studies because of a wide variety of factors related to the disease, patients, study design, and products. OBJECTIVE: The objective of this study was to characterize this variability and identify the major factors that contribute to these fluctuations. METHODS: A systematic literature review was conducted using the MEDLINE, Clinicaltrials.gov, and Cochrane Library databases. Studies that reported the immunogenicity rates of adalimumab were selected, and data pertaining to publication details, study characteristics, characteristics of the cohort at baseline, and immunogenicity were extracted. Records were sorted according to the immunogenicity assay type, and mean immunogenicity values for each assay type were calculated. Normalised immunogenicity was calculated for each report by subtracting the appropriate mean immunogenicity value. Collected data were subjected to statistical analysis, namely analysis of variance (ANOVA) and principal component analysis, to unveil immunogenicity rate patterns across studies from a multivariate perspective. RESULTS: In total, 130 publications were identified, from which 165 data records were extracted and included in the analysis. The immunogenicity rates of adalimumab averaged 24.9% across studies and varied significantly over time, ranging between 0 and 87%. An increase across time in the reported immunogenicity rates was detected, and the assay used to detect anti-adalimumab antibodies was a significant (but not exclusive) contributor to this trend. Furthermore, the principal components analysis revealed that the type of study and the exposure time were associated with the assay-normalised immunogenicity rates of adalimumab. Nonetheless, neither these nor the remaining factors included in this analysis seem to contribute to the temporal increase in reported immunogenicity rates. CONCLUSIONS: Future studies that evaluate the patient-, product-, and disease-related factors behind the immunogenicity of adalimumab are required because the evidence published so far does not completely explain the temporal increase in immunogenicity rates detected in this analysis.

Analysis of Immunogenicity Data in the Product Information of Biological Drugs: A Need to Report Immunogenicity Data Systematically.

OBJECTIVE: The aim of this analysis was to evaluate whether the current unsystematic assessment leads to sufficient reporting of immunogenicity-related information in the Summary of Product Characteristics (SmPCs) of biological products approved in the European market. METHODS: Immunogenicity-related information was identified and extracted from a group of 72 biological drugs that complied with drug-selection criteria. Afterwards, 12 dichotomous questions were proposed to evaluate whether any issues are being commonly neglected. RESULTS: Most SmPCs (92%) do not have any recommendations on how to report immunogenicity-related adverse drug reactions by patients or healthcare professionals. Furthermore, 80% of SmPCs do not identify the assay used to assess the reported immunogenicity rates, while 81% do not address the possible impact of immunogenicity on their drug's pharmacokinetics. It was also identified that a group factor (i.e. older drugs' SmPCs) could be influencing how/which issues were being addressed by newer drugs' SmPCs. To transform SmPCs into useful tools when an immunogenic response occurs, a proposal on how to report immunogenicity-related information in the SmPCs of biological products is advanced. This decision tree should contribute towards increasing the quality and transparency of the immunogenicity-related information being reported in the SmPCs, thus leading to better informed medical decisions. CONCLUSIONS: Based on these results, an unsystematic assessment does not yield enough reporting across products and thus immunogenicity-related information should be reported in a systematic way. Further guidance about reporting immunogenicity-related information is required, otherwise SmPCs will not be the basis of information for healthcare professionals on how to use a biological product safely and effectively.