- Current research efforts require a broad range of immune reagents, but those available for pigs are limited. The goal of this study Bio Med Frontiers was to generate priority immune reagents for pigs and pipeline them for marketing.
- Our efforts were aimed at the expression of soluble swine cytokines and the production of panels of monoclonal antibodies (mAbs) to these proteins. Swine interleukin-17A (IL-17A) and Interferon-gamma (IFNγ) recombinant proteins were produced using yeast expression and used for monoclonal antibody (mAb) production resulting in panels of mAbs.
- We screened each mAb for cross-species reactivity with orthologs of IL-17A or IFNγ and checked each mAb for inhibition by other related mAbs, to assign mAb antigenic determinants.
- For porcine IL-17A, the characterization of a panel of 10 mAbs identified eight different antigenic determinants; interestingly, most of the mAbs cross-reacted with the dolphin recombinant ortholog.
- Likewise, the characterization of a panel of nine anti-PoIFNγ mAbs identified four different determinants; most of the mAbs cross-reacted with dolphin, bovine, and caprine recombinant orthologs.
- There was a unique reaction of one anti-PoIFNγ mAb that cross-reacted with the zebrafish recombinant ortholog. The αIL-17A mAbs were used to develop a quantitative sandwich ELISA detecting the yeast expressed protein as well as native IL-17A in stimulated peripheral blood mononuclear cell (PBMC) supernatants.
- Our analyses showed that phorbol myristate acetate/ionomycin stimulation of PBMC induced significant expression of IL-17A by CD3+ T cells as detected by several of our mAbs. These new mAbs expand opportunities for immunology research in swine.
A Case With New-onset Neuromyelitis Optica Spectrum Disorder Following COVID-19 mRNA BNT162b2 Vaccination.
In the midst of the coronavirus disease of 2019 pandemic, active immunization by effective vaccination gained utmost importance in terms of global health. The messenger RNA (mRNA) vaccines are novel strategies requiring clinical surveillance for adverse events. https://biomedfrontiers.org/Research Antibodies
We report a 43-year-old previously healthy female with an optic neuritis attack 24 hours following immunization with the second dose of coronavirus disease of 2019 mRNA BNT162b2 vaccine.
A second transverse myelitis attack together with an elevated anti-AQP-4 antibody titer confirmed the diagnosis of neuromyelitis optica spectrum disorder.
Our case identifies the BNT162b2 vaccine as a possible trigger for neuromyelitis optica spectrum disorder.
This rare and potentially coincidental event has no implications for vaccine administration practices.
However, further research is needed to elucidate the effects of mRNA vaccines on humoral and cell-mediated immunity.
Progress in prevention and control of Nipah virus disease
Nipah virus disease (NVD) is a newly emerged zoonosis with a case fatality rate of 40%-75%.
NVD is a severe threat to human health and the development of livestock farming. NVD has become one of the emerging infectious diseases with great concern globally during more than 20 years. Nipah virus (NiV) is a pathogen for NVD, the natural host of which is Fruit bats of the Pteropodidae family.
The clinical spectrum of NiV infection is broad, including asymptomatic infection, acute respiratory infection, fatal encephalitis, and even death.
Since NiV was first identified in Malaysia in 1999, it has been prevalent mainly in Southeast Asia and South Asia. NiV is primarily transmitted to humans through bat-pig-human, contaminated food.
Currently, there are no specific therapeutic drugs and vaccines for NVD. Although there are no cases of NVD reported in China, which has close personnel and trade exchanges with major NVD-endemic countries, and NiV antibody has also been detected in relevant bats.
There is a potential risk of importing NVD and domestic outbreaks in the future in this country. This paper provides a systematic review of the research progress in the prevention and control of NVD etiology, epidemiology, clinical manifestations and laboratory diagnosis to help relevant staff to understand NVD more comprehensively and systematically.
Conformation-dependent anti-Aβ monoclonal antibody signatures of disease status and severity in the urine of women with preeclampsia.
- Prior research has shown that urine of women with preeclampsia (PE) contains amyloid-like aggregates that are congophilic (exhibit affinity for the amyloidophilic dye Congo red) and immunoreactive with A11, a polyclonal serum against prefibrillar β-amyloid oligomers, thereby supporting pathogenic similarity between PE and protein conformational disorders such as Alzheimer’s and prion disease.
- The objective of this study was to interrogate PE urine using monoclonal antibodies with previously characterized A11-like epitopes. Over 100 conformation-dependent monoclonals were screened and three (mA11-09, mA11-89, and mA11-205) selected for further confirmation in 196 urine samples grouped as follows: severe features PE (sPE, n = 114), PE without severe features (mPE, n = 30), chronic hypertension (crHTN, n = 14) and normotensive pregnant control (P-CRL, n = 38).
- We showed that the selected conformation-specific monoclonals distinguished among patients with varying severities of PE from P-CRL and patients with crHTN. By use of latent class analysis (LCA) we identified three classes of subjects: Class 1 (n = 94) comprised patients whose urine was both congophilic and reactive with the monoclonals.
- These women were more likely diagnosed with early-onset sPE and had severe hypertension and proteinuria; Class 2 patients (n = 55) were negative for congophilia and against the antibodies. These were predominantly P-CRL and crHTN patients.
- Lastly, Class 3 patients (n = 48) were positive for urine congophilia, albeit at lower intensity, but negative for monoclonal immunoreactivities. These women were diagnosed primarily as mPE or late-onset sPE. Collectively, our study validates conformation-dependent Aβ imunoreactivity of PE urine which in conjunction to urine congophilia may represent an additional indicator of disease severity.
The Pandemic Brain: neuroinflammation in non-infected individuals during the COVID-19 pandemic.
While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored.
However, a global increase in the prevalence of fatigue, brain fog, depression, and other “sickness behavior”-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus.
We compared fifty-seven ‘Pre-Pandemic’ and fifteen ‘Pandemic’ datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies.
We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomic, and serologic testing to uncover links between pandemic-related stressors and neuroinflammation.
Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects.
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The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus, and precuneus (physical fatigue), compared to those reporting little/no symptoms.
Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions.
This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings.