Perspectives on Assembling Coronavirus Spikes on Fiber Optics to Reveal Broadly Recognizing Antibodies and Generate a Universal Coronavirus Detector

In time of COVID-19 biological detection technologies are of crucial relevance. We propose here the use of state of the art optical fiber biosensors to address two aspects of the fight against SARS-CoV-2 and other pandemic human coronaviruses (HCoVs). Fiber optic biosensors functionalized with HCoV spikes could be used to discover broadly neutralizing antibodies (bnAbs) effective against known HCoVs (SARS-CoV, MERS-CoV and SARS-CoV-2) and likely future ones. In turn, identified bnAbs, once immobilized onto fiber optic biosensors, should be capable to detect HCoVs as diagnostic and environmental sensing devices. The therapeutic and preventative value of bnAbs is immense as they can be used for passive immunization and for the educated development of a universal vaccine (active immunization). Hence, HCoV bnAbs represent an extremely important resource for future preparedness against coronavirus-borne pandemics. Furthermore, the assembly of bnAb-based biosensors constitutes an innovative approach to counteract public health threats, as it bears diagnostic competence additional to environmental detection of a range of pandemic strains. This concept can be extended to different pandemic viruses, as well as bio-warfare threats that entail existing, emerging and extinct viruses (e.g., the smallpox-causing Variola virus). We report here the forefront fiber optic biosensor technology that could be implemented to achieve these aims.

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Fiber Optic Sensing Technologies for Battery Management Systems and Energy Storage Applications

Sensors ◽

10.3390/s21041397 ◽

2021 ◽

Vol 21 (4) ◽

pp. 1397

Author(s):

Yang-Duan Su ◽

Yuliya Preger ◽

Hannah Burroughs ◽

Chenhu Sun ◽

Paul Ohodnicki

Keyword(s):

Energy Storage ◽

Fiber Optics ◽

Fiber Optic ◽

Gas Sensing ◽

Fiber Optic Sensors ◽

Management Systems ◽

Practical Implementation ◽

Battery Management ◽

Battery Management Systems ◽

Battery Systems

Applications of fiber optic sensors to battery monitoring have been increasing due to the growing need of enhanced battery management systems with accurate state estimations. The goal of this review is to discuss the advancements enabling the practical implementation of battery internal parameter measurements including local temperature, strain, pressure, and refractive index for general operation, as well as the external measurements such as temperature gradients and vent gas sensing for thermal runaway imminent detection. A reasonable matching is discussed between fiber optic sensors of different range capabilities with battery systems of three levels of scales, namely electric vehicle and heavy-duty electric truck battery packs, and grid-scale battery systems. The advantages of fiber optic sensors over electrical sensors are discussed, while electrochemical stability issues of fiber-implanted batteries are critically assessed. This review also includes the estimated sensing system costs for typical fiber optic sensors and identifies the high interrogation cost as one of the limitations in their practical deployment into batteries. Finally, future perspectives are considered in the implementation of fiber optics into high-value battery applications such as grid-scale energy storage fault detection and prediction systems.

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Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Nature Communications ◽

10.1038/s41467-020-20879-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wayne D. Harshbarger ◽

Derrick Deming ◽

Gordon J. Lockbaum ◽

Nattapol Attatippaholkun ◽

Maliwan Kamkaew ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Influenza A ◽

Critical Role ◽

Binding Activity ◽

Human Antibody ◽

Broadly Neutralizing Antibodies ◽

Influenza A Viruses ◽

Universal Vaccine ◽

Structural Details ◽

Structural Solution

AbstractBroadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.

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Microanchored borehole fiber optics allows strain profiling of the shallow subsurface

Scientific Reports ◽

10.1038/s41598-021-88526-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cheng-Cheng Zhang ◽

Bin Shi ◽

Song Zhang ◽

Kai Gu ◽

Su-Ping Liu ◽

...

Keyword(s):

Fiber Optics ◽

Field Experiments ◽

Fiber Optic ◽

Strain Sensing ◽

Near Surface ◽

Shallow Subsurface ◽

Buried Cables ◽

Capacity Theory ◽

Confining Pressures ◽

Strain Determination

AbstractVertical deformation profiles of subterranean geological formations are conventionally measured by borehole extensometry. Distributed strain sensing (DSS) paired with fiber-optic cables installed in the ground opens up possibilities for acquiring high-resolution static and quasistatic strain profiles of deforming strata, but it is currently limited by reduced data quality due to complicated patterns of interaction between the buried cables and their surroundings, especially in upper soil layers under low confining pressures. Extending recent DSS studies, we present an improved approach using microanchored fiber-optic cables—designed to optimize ground-to-cable coupling at the near surface—for strain determination along entire lengths of vertical boreholes. We proposed a novel criterion for soil–cable coupling evaluation based on the geotechnical bearing capacity theory. We applied this enhanced methodology to monitor groundwater-related vertical motions in both laboratory and field experiments. Corroborating extensometer recordings, acquired simultaneously, validated fiber optically determined displacements, suggesting microanchored DSS as an improved means for detecting and monitoring shallow subsurface strain profiles.

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The Road towards Polyclonal Anti-SARS-CoV-2 Immunoglobulins (Hyperimmune Serum) for Passive Immunization in COVID-19

Life ◽

10.3390/life11020144 ◽

2021 ◽

Vol 11 (2) ◽

pp. 144

Author(s):

Daniele Focosi ◽

Marco Tuccori ◽

Massimo Franchini

Keyword(s):

Neutralizing Antibodies ◽

Passive Immunization ◽

Spike Protein ◽

Controlled Trials ◽

Disease Course ◽

Early Disease ◽

Hyperimmune Serum ◽

The Road ◽

Randomized Controlled ◽

Pros And Cons

Effective treatments specific for COVID-19 are still lacking. In the setting of passive immunotherapies based on neutralizing antibodies (nAbs), randomized controlled trials of COVID-19 convalescent plasma (CCP) anti-SARS-CoV-2 Spike protein monoclonal antibodies (mAb), which have been granted emergency use authorization, have suggested benefit in early disease course (less than 72 hours from symptoms and seronegative). Meanwhile, polyclonal immunoglobulins (i.e., hyperimmune serum), derived either from CCP donations or from animals immunized with SARS-CoV-2 antigens, are likely to become the next nAb-derived candidate. We here discuss the pros and cons of hyperimmune serum versus CCP and mAb, and summarize the ongoing clinical trials of COVID-19 hyperimmune sera.

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A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol

BMC Pulmonary Medicine ◽

10.1186/s12890-020-01361-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Benoît Misset ◽

Eric Hoste ◽

Anne-Françoise Donneau ◽

David Grimaldi ◽

Geert Meyfroidt ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Failure ◽

Neutralizing Antibodies ◽

Ethical Issues ◽

High Titer ◽

Passive Immunization ◽

University Hospital ◽

Optimal Time ◽

Relative Reduction ◽

Number Of Patients

Abstract Background The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. Methods We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and β risk of 20 percent. Discussion This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences. Funding and registration The trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004 Trial registration Clinicaltrials.gov registration number NCT04558476. Registered 14 September 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476

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A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00588-2 ◽

2021 ◽

Author(s):

Vincent Legros ◽

Solène Denolly ◽

Manon Vogrig ◽

Bertrand Boson ◽

Eglantine Siret ◽

...

Keyword(s):

Intensive Care ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Surface Protein ◽

Humoral Response ◽

Neutralizing Antibody ◽

Rapid Decline ◽

Serum Samples ◽

Immune Correlates ◽

Human Coronaviruses

AbstractUnderstanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

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Respiratory Syncytial Virus (RSV) Diseases

10.33442/vt202160 ◽

2022 ◽

Author(s):

Heinz-Josef Schmitt ◽

Khrystyna Hrynkevych

Keyword(s):

Respiratory Syncytial Virus ◽

Rna Virus ◽

Passive Immunization ◽

Active Immunization ◽

F Protein ◽

Hospitalization Rates ◽

Syncytial Virus ◽

Repeated Infections ◽

Long Acting ◽

Underlying Diseases

The respiratory syncytial virus (RSV) is an RNA virus that causes annual ARI outbreaks during winter with mild URTI in the general population, but with severe LRTI particularly among young children (bronchiolitis), patients with underlying diseases and people >65 years of age. RSV does not induce a long-lasting protective immunity and repeated infections throughout life are the norm. Basically, all children have been infected by 2 years of age and of those hospitalized, >50% are <3 months and 75% are <6 months of age. The overall CFR is 1/500. For adults ≥65 years, RSV hospitalization rates are 90–250/105. There is no specific therapy, general preventive measures include general hygiene and isolation/separation of patients. A monoclonal anti-F-protein antibody is available for passive immunization of selected high-risk children. It requires monthly injections, comes at a high cost and has limited efficacy (50% against RSV hospitalization). Active immunization failed in the past, probably as the post-fusion conformation of the F-protein was used. Long-acting monoclonal antibodies (for infants) as well as stabilized pre-fusion F-protein vaccines (for immunization of pregnant women, children, older adults) produced on various platforms are in late stages of clinical development.

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Remembering As We Look Ahead: The Three E's and Firearm Injuries

PEDIATRICS ◽

10.1542/peds.88.2.379 ◽

1991 ◽

Vol 88 (2) ◽

pp. 379-383

Author(s):

MARK D. WIDOME

Keyword(s):

Young Child ◽

American Academy ◽

Passive Immunization ◽

Active Immunization ◽

Accident Prevention ◽

Safety Education ◽

Childhood Injury ◽

Firearm Injuries ◽

American Academy Of Pediatrics ◽

Look Ahead

There was a little man, and he had a little gun, And his bullets were made of lead, lead, lead; He went to the brook, and he saw a little duck, And he shot it through the head, head, head. —Mother Goose Four decades ago, Harry Dietrich,1 a member of the American Academy of Pediatrics' newly established Accident Prevention Committee, described a developmentally based approach to the prevention of childhood injury. Dietrich stressed the great need for protection ("passive immunization") for the young child and for safety education ("active immunization") as the child matures. It was also in the early 1950s that George Wheatley, the first chairman of the Accident Prevention Committee, popularized the "three E's"2—education, enforcement, and engineering—as a framework for developing and categorizing strategies to prevent injuries.

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Antisera, Toxoids, Vaccines and Tuberculins in Prophylaxis and Treatment

PEDIATRICS ◽

10.1542/peds.23.2.430 ◽

1959 ◽

Vol 23 (2) ◽

pp. 430-430

Author(s):

C. ARDEN MILLER

Keyword(s):

Infectious Diseases ◽

Passive Immunization ◽

Active Immunization ◽

Biological Products

This book begins: "Biological products used in infectious diseases may be divided into three groups, namely: 1) Sera of various types for prophylaxis and treatment by passive immunization; 2) Prophylactics, such as toxins, toxoids, and vaccines (both bacterial and viral), for active immunization; 3) Diagnostic products, such as diluted toxins and tuberculins, used by the clinician to detect the presence or absence of immunity and also of allergy. Most of these materials come within the scope of this book.

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Effect of immunization with prostaglandin metabolites on gastrointestinal ulceration

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.255.6.g723 ◽

1988 ◽

Vol 255 (6) ◽

pp. G723-G730 ◽

Cited By ~ 1

Author(s):

J. S. Redfern ◽

E. Lee ◽

M. Feldman

Keyword(s):

Platelet Aggregation ◽

Prostaglandin E2 ◽

Passive Immunization ◽

Adenosine Diphosphate ◽

Active Immunization ◽

Gastric Ulceration ◽

Separate Group ◽

Control Plasma ◽

Gastrointestinal Ulceration ◽

Donor Plasma

Active immunization of rabbits with a 6-ketoprostaglandin F1 alpha-thyroglobulin conjugate induced gastrointestinal ulceration, whereas active immunization of rabbits with 13,14-dihydro-15-keto prostaglandin E2-thyroglobulin conjugate or with thyroglobulin alone did not result in ulceration. Passive immunization of a separate group of rabbits with 6-ketoprostaglandin F1 alpha-hyperimmune plasma, obtained from actively 6-ketoprostaglandin F1 alpha-immunized donor rabbits that had ulcers, induced gastric ulceration within 9 days, whereas passive immunization of rabbits with control plasma, obtained from donor rabbits actively immunized with thyroglobulin alone, did not induce ulceration. Ulcerogenic donor plasma containing antibody to 6-ketoprostaglandin F1 alpha neutralized the inhibitory actions of prostacyclin on adenosine diphosphate-induced platelet aggregation, indicating that this antibody cross-reacted with prostacyclin. In contrast, plasma containing antibodies to 13,14-dihydro-15-ketoprostaglandin E2 cross-reacted only slightly with prostaglandin E2. Thus antibodies to inactive metabolites of prostaglandins induce ulceration only if these antibodies cross-react with an endogenous, "cytoprotective" prostaglandin.

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