Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response

Additional file 1: Fig. S1. Components and assembly of the PTE module for innate responses. (A) Top panel—in vivo monocytes continuously emigrate from the blood into peripheral tissues with a half-life in the blood of ~1 day. Bottom panel: In vitro generation of cytokine derived DCs from monocytes involves the addition of IL-4 and GM-CSF and culture for 7–11 days. (B) Schematic of the components of a MIMIC-PTE module. In the 3D PTE, differentiation occurs in hours to about 2 days triggered by migration into and out of (reverse migration) through the endothelium: a process reminiscent of the movement of cells from tissues into lymphatic vessels

Coupling sensitive \u3cem\u3ein vitro\u3c/em\u3e and in silico techniques to assess cross-reactive CD4\u3csup\u3e+\u3c/sup\u3e T cells against the swine-origin H1N1 influenza virus

The outbreak of the novel swine-origin H1N1 influenza in the spring of 2009 took epidemiologists, immunologists, and vaccinologists by surprise and galvanized a massive worldwide effort to produce millions of vaccine doses to protect against this single virus strain. Of particular concern was the apparent lack of pre-existing antibody capable of eliciting cross-protective immunity against this novel virus, which fueled fears this strain would trigger a particularly far-reaching and lethal pandemic. Given that disease caused by the swine-origin virus was far less severe than expected, we hypothesized cellular immunity to cross-conserved T cell epitopes might have played a significant role in protecting against the pandemic H1N1 in the absence of cross-reactive humoral immunity. In a published study, we used an immunoinformatics approach to predict a number of CD4+ T cell epitopes are conserved between the 2008–2009 seasonal H1N1 vaccine strain and pandemic H1N1 (A/California/04/2009) hemagglutinin proteins. Here, we provide results from biological studies using PBMCs from human donors not exposed to the pandemic virus to demonstrate that pre-existing CD4+ T cells can elicit cross-reactive effector responses against the pandemic H1N1 virus. As well, we show our computational tools were 80–90% accurate in predicting CD4+ T cell epitopes and their HLA-DRB1-dependent response profiles in donors that were chosen at random for HLA haplotype. Combined, these results confirm the power of coupling immunoinformatics to define broadly reactive CD4+ T cell epitopes with highly sensitive in vitro biological assays to verify these in silico predictions as a means to understand human cellular immunity, including cross-protective responses, and to define CD4+ T cell epitopes for potential vaccination efforts against future influenza viruses and other pathogens

Molecular and crystalline microstructure of ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) ultrathin films on bare and self-assembled monolayer-modified au substrates

We investigate the molecular and microdomain structure of ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) P(VDF-TrFE) copolymer thin films spin-coated on bare and self-assembled monolayers (SAMs)-modified An substrates. The two types of films display similar crystal morphologies with edge-on needlelike shaped crystalline microdomains. They have, however, a different structure depending on the substrate. When the P(VDF-TrFE) films are deposited on a bare, unmodified An surface, the P(VDF-TrFE) films preferentially have a (110) contact plane with the substrate but a (100) contact plane when deposited on the An surface modified by SAMs. The polar b-axis, along which the ferroelectric polarization is oriented, is therefore tilted to the film (and substrate) surface normal at 30 and 90 degrees, respectively. In particular, the orientation of the polar b-axis tilted at some 90 degrees to the normal of the polymer films on a CH3 terminated SAM modified Au surface explains the smaller remanent polarization at low initial electrical biasclose242

Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post-COVID-19 syndrome.

BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation