Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites.

Resident memory B (BRM) cells develop and persist in the lungs of influenza-infected mice and humans; however, their contribution to recall responses has not been defined. Here, we used two-photon microscopy to visualize BRM cells within the lungs of influenza -virus immune and reinfected mice. Prior to re-exposure, BRM cells were sparsely scattered throughout the tissue, displaying limited motility. Within 24 h of rechallenge, these cells increased their migratory capacity, localized to infected sites, and subsequently differentiated into plasma cells. Alveolar macrophages mediated this process, in part by inducing expression of chemokines CXCL9 and CXCL10 from infiltrating inflammatory cells. This led to the recruitment of chemokine receptor CXCR3-expressing BRM cells to infected regions and increased local antibody concentrations. Our study uncovers spatiotemporal mechanisms that regulate lung BRM cell reactivation and demonstrates their capacity to rapidly deliver antibodies in a highly localized manner to sites of viral replication.

A systematic review and meta-analysis of the accuracy of SARS-COV-2 IGM and IGG tests in individuals with COVID-19.

INTRODUCTION: Active SARS-CoV-2 infection is confirmed mainly through the detection of viral nucleic acid via the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Methods to assess humoral responses contribute to the monitoring of the disease and confirmation of exposure to the virus. OBJECTIVE: To evaluate the accuracy of tests for IgM and IgG antibodies for SARS-CoV-2 infection confirmed by RT-PCR and utility as complementary data for immunosurveillance. METHODS: Literature research was performed by searching the terms "COVID-19", "COVID-19 diagnostic testing" and "test" in the databases MEDLINE, EMBASE, Cochrane Library, Web of Science and Cumulative Index to Nursing and Allied Health Literature to search for potentially eligible observational studies without language restrictions published up to September 2020. RESULTS: The pooled sensitivity and specificity, regardless of collection moment, was 80.0% (CI 95% 72.0-86.0) and 97.0% (CI 95% 94.0-98.0) for "IgM and/or IgG", respectively. Serology considering immunoglobulins M and G together had a high accuracy performance on "fifteenth day and after": sensitivity and specificity was 91.0% (CI 95% 85.0-94.0) and 98.0% (CI 95% 95.0-99.0) respectively, DOR 461 and AUC 0.98. CONCLUSION: This study shows that serology is a group of tests with high accuracy, mainly following the second week after infection.

Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles.

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.