Publications by authors named "Ralf Wagner"

189 Publications

Association between Reactogenicity and Immunogenicity after Vaccination with BNT162b2.

Vaccines (Basel) 2021 Sep 27;9(10). Epub 2021 Sep 27.

Institute for Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

It is not clear whether there is an association between adverse reactions and immune response after vaccination. Seven hundred and thirty-five vaccinees from our University Medical Center vaccination clinic provided information about sex, age and adverse reactions after first and second vaccination with BNT162b2. Adverse reactions were categorized into three groups: no or minor on the injection side, moderate (not further classified) and severe-defined as any symptom(s) resulting in sick leave. We chose 38 vaccinees with the most severe adverse reactions and compared their humoral and T-cell-mediated immune responses after second vaccination with those of 38 sex and age matched controls without or only minor injection-side related adverse reactions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-receptor binding domain (RBD) IgG titers were detectable in all participants (median 5528; range 958-26,285). Men with severe adverse reactions had 1.5-fold higher median SARS-CoV-2 RBD IgG titers compared to men without adverse reactions (median 7406 versus 4793; < 0.001). Similarly; neutralization activity was significantly higher in men with severe adverse reactions (half maximal inhibitory concentrations (IC) median 769 versus 485; < 0.001). Reactogenicity did not influence humoral immune response in women nor T-cell-mediated immune response in any sex. To conclude; adverse reactions after vaccination with BNT162b2 do influence humoral immune response yet only in men and are not a prerequisite for a robust antibody response.
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http://dx.doi.org/10.3390/vaccines9101089DOI Listing
September 2021

Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests-A Population-Based Evaluation.

Diagnostics (Basel) 2021 Oct 6;11(10). Epub 2021 Oct 6.

Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany.

Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test development and validation, spectrum bias has to be considered when moving from a "test establishment setting" to population-based settings, in which antibody testing is currently implemented. To provide insights into the presence and magnitude of spectrum bias and to estimate performance measures of antibody testing in a population-based environment, we compared SARS-CoV-2 neutralization to a battery of serological tests and latent class analyses (LCA) in a subgroup ( = 856) of the larger population based TiKoCo-19 cohort ( = 4185). Regarding spectrum bias, we could proof notable differences in test sensitivities and specificities when moving to a population-based setting, with larger effects visible in earlier registered tests. While in the population-based setting the two Roche ELECSYS anti-SARS-CoV-2 tests outperformed every other test and even LCA regarding sensitivity and specificity in dichotomous testing, they didn't provide satisfying quantitative correlation with neutralization capacity. In contrast, our in-house anti SARS-CoV-2-Spike receptor binding domain (RBD) IgG-ELISA (enzyme-linked-immunosorbant assay) though inferior in dichotomous testing, provided satisfactory quantitative correlation and may thus represent a better correlate of protection. In summary, all tests, led by the two Roche tests, provided sufficient accuracy for dichotomous identification of neutralizing sera, with increasing spectrum bias visible in earlier registered tests, while the majority of tests, except the RBD-ELISA, didn't provide satisfactory quantitative correlations.
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http://dx.doi.org/10.3390/diagnostics11101843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534748PMC
October 2021

Symptoms, SARS-CoV-2 Antibodies, and Neutralization Capacity in a Cross Sectional-Population of German Children.

Front Pediatr 2021 4;9:678937. Epub 2021 Oct 4.

University Children's Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany.

Children and youth are affected rather mildly in the acute phase of COVID-19 and thus, SARS-CoV-2 infection infection may easily be overlooked. In the light of current discussions on the vaccinations of children it seems necessary to better identify children who are immune against SARS-CoV-2 due to a previous infection and to better understand COVID-19 related immune reactions in children. In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a) randomly, if they had an appointment for a regular health check-up or (b) if parents and children volunteered and actively wanted to participate in the study. Symptoms were recorded and two antibody tests were performed in parallel directed against S (in house test) and N (Roche Elecsys) viral proteins. In children with antibody response in either test, neutralization activity was determined. We identified antibodies against SARS-CoV-2 in 162 of 2,832 eligible children (5.7%) between end of May and end of July 2020 in three, in part strongly affected regions of Bavaria in the first wave of the pandemic. Approximately 60% of antibody positive children ( = 97) showed high levels (>97th percentile) of antibodies against N-protein, and for the S-protein, similar results were found. Sufficient neutralizing activity was detected for only 135 antibody positive children (86%), irrespective of age and sex. Initial COVID-19 symptoms were unspecific in children except for the loss of smell and taste and unrelated to antibody responses or neutralization capacity. Approximately 30% of PCR positive children did not show seroconversion in our small subsample in which PCR tests were performed. Symptoms of SARS-CoV-2 infections are unspecific in children and antibody responses show a dichotomous structure with strong responses in many and no detectable antibodies in PCR positive children and missing neutralization activity in a relevant proportion of the young population.
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http://dx.doi.org/10.3389/fped.2021.678937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522552PMC
October 2021

Immunity after COVID-19 and vaccination: follow-up study over 1 year among medical personnel.

Infection 2021 Sep 25. Epub 2021 Sep 25.

Institute for Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.

Background: The long-term course of immunity among individuals with a history of COVID-19, in particular among those who received a booster vaccination, has not been well defined so far.

Methods: SARS-CoV-2-specific antibody levels were measured by ELISA over 1 year among 136 health care workers infected during the first COVID-19 wave and in a subgroup after booster vaccination approximately 1 year later. Furthermore, spike-protein-reactive memory T cells were quantified approximately 7 months after the infection and after booster vaccination. Thirty healthy individuals without history of COVID-19 who were routinely vaccinated served as controls.

Results: Levels of SARS-CoV-2-specific IgM- and IgA-antibodies showed a rapid decay over time, whereas IgG-antibody levels decreased more slowly. Among individuals with history of COVID-19, booster vaccination induced very high IgG- and to a lesser degree IgA-antibodies. Antibody levels were significantly higher after booster vaccination than after recovery from COVID-19. After vaccination with a two-dose schedule, healthy control subjects developed similar antibody levels as compared to individuals with history of COVID-19 and booster vaccination. SARS-CoV-2-specific memory T cell counts did not correlate with antibody levels. None of the study participants suffered from a reinfection.

Conclusions: Booster vaccination induces high antibody levels in individuals with a history of COVID-19 that exceeds by far levels observed after recovery. SARS-CoV-2-specific antibody levels of similar magnitude were achieved in healthy, COVID-19-naïve individuals after routine two-dose vaccination.
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http://dx.doi.org/10.1007/s15010-021-01703-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475821PMC
September 2021

Coronavirus Pseudotypes for All Circulating Human Coronaviruses for Quantification of Cross-Neutralizing Antibody Responses.

Viruses 2021 08 10;13(8). Epub 2021 Aug 10.

Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.

The novel coronavirus SARS-CoV-2 is the seventh identified human coronavirus. Understanding the extent of pre-existing immunity induced by seropositivity to endemic seasonal coronaviruses and the impact of cross-reactivity on COVID-19 disease progression remains a key research question in immunity to SARS-CoV-2 and the immunopathology of COVID-2019 disease. This paper describes a panel of lentiviral pseudotypes bearing the spike (S) proteins for each of the seven human coronaviruses (HCoVs), generated under similar conditions optimized for high titre production allowing a high-throughput investigation of antibody neutralization breadth. Optimal production conditions and most readily available permissive target cell lines were determined for spike-mediated entry by each HCoV pseudotype: SARS-CoV-1, SARS-CoV-2 and HCoV-NL63 best transduced HEK293T/17 cells transfected with ACE2 and TMPRSS2, HCoV-229E and MERS-CoV preferentially entered HUH7 cells, and CHO cells were most permissive for the seasonal betacoronavirus HCoV-HKU1. Entry of ACE2 using pseudotypes was enhanced by ACE2 and TMPRSS2 expression in target cells, whilst TMPRSS2 transfection rendered HEK293T/17 cells permissive for HCoV-HKU1 and HCoV-OC43 entry. Additionally, pseudotype viruses were produced bearing additional coronavirus surface proteins, including the SARS-CoV-2 Envelope (E) and Membrane (M) proteins and HCoV-OC43/HCoV-HKU1 Haemagglutinin-Esterase (HE) proteins. This panel of lentiviral pseudotypes provides a safe, rapidly quantifiable and high-throughput tool for serological comparison of pan-coronavirus neutralizing responses; this can be used to elucidate antibody dynamics against individual coronaviruses and the effects of antibody cross-reactivity on clinical outcome following natural infection or vaccination.
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http://dx.doi.org/10.3390/v13081579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402765PMC
August 2021

Influence of Oral Health Care Systems on Future Career Environment of Dental Students in Europe.

Int J Environ Res Public Health 2021 08 5;18(16). Epub 2021 Aug 5.

Department of Restorative, Preventive and Pediatric Dentistry, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland.

Oral healthcare is organized subsidiarily and independently by nation states in Europe and also within the EU and consequently, major differences between the nation states and the various oral healthcare systems in Europe are present. The socialization in the respective catchment area can have an impact on the job choice and the perception of employment opportunities of different professional groups. Therefore, the purpose of this survey was to elucidate the influence of different oral healthcare systems on students living or studying in the respective catchment area. A questionnaire (in English, French, German, Italian, and Spanish) with 18 different components was administered. Data on gender, age, country of origin, university, semester, nationality, expected time of graduation, and forecast for future professional practices were gathered. In addition, 3851 students participated (2863 f/988 m). The sample distribution was uneven with predominantly Bismarckian and Southern European System participants. The National oral health care system was statistically significantly linked ( < 0.01) to the ownership period of a dental practice. Students in Bismarckian and Nordic systems tended to find their own practice earlier than in the Beverdigian system or Southern European and Transitional-East European systems. An association between the oral health care system and vocational training was inhomogeneous, but also significantly different ( < 0.01). The majority (47.51%, = 1555) would like to work in their own practice, 18.95% ( = 621) want to establish a practice with two or more owners. It was striking that no student would like to work in the investor practice/practice chain of both Nordic, Beveridgian and Transitional-East European countries systems ( < 0.01). The oral health care system in which a dental student grows up/resides/studies influences the career choice/perception of future professional practice.
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http://dx.doi.org/10.3390/ijerph18168292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393998PMC
August 2021

Stepwise Conformational Stabilization of a HIV-1 Clade C Consensus Envelope Trimer Immunogen Impacts the Profile of Vaccine-Induced Antibody Responses.

Vaccines (Basel) 2021 Jul 6;9(7). Epub 2021 Jul 6.

Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, Germany.

Stabilization of the HIV-1 Envelope glycoprotein trimer (Env) in its native pre-fusion closed conformation is regarded as one of several requirements for the induction of neutralizing antibody (nAb) responses, which, in turn, will most likely be a prerequisite for the development of an efficacious preventive vaccine. Here, we systematically analyzed how the stepwise stabilization of a clade C consensus (ConC) Env immunogen impacts biochemical and biophysical protein traits such as antigenicity, thermal stability, structural integrity, and particle size distribution. The increasing degree of conformational rigidification positively correlates with favorable protein characteristics, leading to optimized homogeneity of the protein preparations, increased thermal stability, and an overall favorable binding profile of structure-dependent broadly neutralizing antibodies (bnAbs) and non-neutralizing antibodies (non-nAbs). We confirmed that increasing the structural integrity and stability of the Env trimers positively correlates with the quality of induced antibody responses by the immunogens. These and other data contribute to the selection of ConCv5 KIKO as novel Env immunogens for use within the European Union's H2020 Research Consortium EHVA (European HIV Alliance) for further preclinical analysis and phase 1 clinical development.
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http://dx.doi.org/10.3390/vaccines9070750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310183PMC
July 2021

Accelerated Development of COVID-19 Vaccines: Technology Platforms, Benefits, and Associated Risks.

Vaccines (Basel) 2021 Jul 6;9(7). Epub 2021 Jul 6.

Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, 63225 Langen, Germany.

Multiple preventive COVID-19 vaccines have been developed during the ongoing SARS coronavirus (CoV) 2 pandemic, utilizing a variety of technology platforms, which have different properties, advantages, and disadvantages. The acceleration in vaccine development required to combat the current pandemic is not at the expense of the necessary regulatory requirements, including robust and comprehensive data collection along with clinical product safety and efficacy evaluation. Due to the previous development of vaccine candidates against the related highly pathogenic coronaviruses SARS-CoV and MERS-CoV, the antigen that elicits immune protection is known: the surface spike protein of SARS-CoV-2 or specific domains encoded in that protein, e.g., the receptor binding domain. From a scientific point of view and in accordance with legal frameworks and regulatory practices, for the approval of a clinic trial, the Paul-Ehrlich-Institut requires preclinical testing of vaccine candidates, including general pharmacology and toxicology as well as immunogenicity. For COVID-19 vaccine candidates, based on existing platform technologies with a sufficiently broad data base, pharmacological-toxicological testing in the case of repeated administration, quantifying systemic distribution, and proof of vaccination protection in animal models can be carried out in parallel to phase 1 or 1/2 clinical trials. To reduce the theoretical risk of an increased respiratory illness through infection-enhancing antibodies or as a result of Th2 polarization and altered cytokine profiles of the immune response following vaccination, which are of specific concern for COVID-19 vaccines, appropriate investigative testing is imperative. In general, phase 1 (vaccine safety) and 2 (dose finding, vaccination schedule) clinical trials can be combined, and combined phase 2/3 trials are recommended to determine safety and efficacy. By applying these fundamental requirements not only for the approval and analysis of clinical trials but also for the regulatory evaluation during the assessment of marketing authorization applications, several efficacious and safe COVID-19 vaccines have been licensed in the EU by unprecedentedly fast and flexible procedures. Procedural and regulatory-scientific aspects of the COVID-19 licensing processes are described in this review.
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http://dx.doi.org/10.3390/vaccines9070747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310218PMC
July 2021

Exploiting Pan Influenza A and Pan Influenza B Pseudotype Libraries for Efficient Vaccine Antigen Selection.

Vaccines (Basel) 2021 Jul 5;9(7). Epub 2021 Jul 5.

Viral Pseudotype Unit, Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Chatham ME4 4BF, UK.

We developed an influenza hemagglutinin (HA) pseudotype library encompassing Influenza A subtypes HA1-18 and Influenza B subtypes (both lineages) to be employed in influenza pseudotype microneutralization (pMN) assays. The pMN is highly sensitive and specific for detecting virus-specific neutralizing antibodies against influenza viruses and can be used to assess antibody functionality in vitro. Here we show the production of these viral HA pseudotypes and their employment as substitutes for wildtype viruses in influenza neutralization assays. We demonstrate their utility in detecting serum responses to vaccination with the ability to evaluate cross-subtype neutralizing responses elicited by specific vaccinating antigens. Our findings may inform further preclinical studies involving immunization dosing regimens in mice and may help in the creation and selection of better antigens for vaccine design. These HA pseudotypes can be harnessed to meet strategic objectives that contribute to the strengthening of global influenza surveillance, expansion of seasonal influenza prevention and control policies, and strengthening pandemic preparedness and response.
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http://dx.doi.org/10.3390/vaccines9070741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310092PMC
July 2021

A pair of noncompeting neutralizing human monoclonal antibodies protecting from disease in a SARS-CoV-2 infection model.

Eur J Immunol 2021 Aug 6. Epub 2021 Aug 6.

Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.

TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
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http://dx.doi.org/10.1002/eji.202149374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420377PMC
August 2021

Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery.

Vaccines (Basel) 2021 Jun 11;9(6). Epub 2021 Jun 11.

Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, Germany.

The delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm and 200 nm silica nanoparticles (SiNPs) to optimize conjugation density and attachment stability. Env was redesigned to enable site-specific cysteine-mediated covalent conjugation while maintaining its structural integrity and antigenicity. Env was anchored to different sized SiNPs with a calculated spacing of 15 nm between adjacent trimers. Both particle sizes exhibited high in vitro stability over a seven-day period. After attachment, 100 nm particles showed better colloidal stability compared to 200 nm particles. Importantly, the antigenic profile of Env was not impaired by surface attachment, indicating that the quaternary structure was maintained. In vitro Env uptake by dendritic cells was significantly enhanced when Env was delivered on the surface of nanoparticles compared to soluble Env. Furthermore, multivalent Env displayed efficiently activated B cells even at Env concentrations in the low nanomolar range. In mice, antibody responses to nanoparticle-coupled Env were stronger compared to the free protein and had equivalent effects at lower doses and without adjuvant.
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http://dx.doi.org/10.3390/vaccines9060642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230641PMC
June 2021

Estimates and Determinants of SARS-Cov-2 Seroprevalence and Infection Fatality Ratio Using Latent Class Analysis: The Population-Based Tirschenreuth Study in the Hardest-Hit German County in Spring 2020.

Viruses 2021 06 10;13(6). Epub 2021 Jun 10.

Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany.

SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020, with particularly high case fatality ratio (CFR). To estimate seroprevalence, underreported infections, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020, we conducted a population-based study including home visits for the elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests. Latent class analysis yielded 8.6% standardized county-wide seroprevalence, a factor of underreported infections of 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the factor of underreported infections was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, and 13.2% for age 70+. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.
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http://dx.doi.org/10.3390/v13061118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230374PMC
June 2021

The HIV 5' Gag Region Displays a Specific Nucleotide Bias Regulating Viral Splicing and Infectivity.

Viruses 2021 05 27;13(6). Epub 2021 May 27.

Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.

Alternative splicing and the expression of intron-containing mRNAs is one hallmark of HIV gene expression. To facilitate the otherwise hampered nuclear export of non-fully processed mRNAs, HIV encodes the Rev protein, which recognizes its intronic response element and fuels the HIV RNAs into the CRM-1-dependent nuclear protein export pathway. Both alternative splicing and Rev-dependency are regulated by the primary HIV RNA sequence. Here, we show that these processes are extremely sensitive to sequence alterations in the 5'coding region of the HIV genomic RNA. Increasing the GC content by insertion of either GFP or silent mutations activates a cryptic splice donor site in , entirely deregulates the viral splicing pattern, and lowers infectivity. Interestingly, an adaptation of the inserted GFP sequence toward an HIV-like nucleotide bias reversed these phenotypes completely. Of note, the adaptation yielded completely different primary sequences although encoding the same amino acids. Thus, the phenotypes solely depend on the nucleotide composition of the two GFP versions. This is a strong indication of an HIV-specific mRNP code in the 5' region wherein the primary RNA sequence bias creates motifs for RNA-binding proteins and controls the fate of the HIV-RNA in terms of viral gene expression and infectivity.
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http://dx.doi.org/10.3390/v13060997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227319PMC
May 2021

IABS/CEPI platform technology webinar: Is it possible to reduce the vaccine development time?

Biologicals 2021 Jun 7;71:55-60. Epub 2021 May 7.

International Alliance for Biological Standardization, IABS, Geneva, Switzerland. Electronic address:

The International Alliance for Biological Standardization and the Coalition for Epidemic Preparedness Innovations organized a joint webinar on the use of platform technologies for vaccine development. To tackle new emerging infectious diseases, including SARS-CoV-2, rapid response platforms, using the same basic components as a backbone, yet adaptable for use against different pathogens by inserting new genetic or protein sequences, are essential. Furthermore, it is evident that development of platform technologies needs to continue, due to the emerging variants of SARS-CoV-2. The objective of the meeting was to discuss techniques for platform manufacturing that have been used for COVID-19 vaccine development, with input from regulatory authorities on their experiences with, and expectations of, the platforms. Industry and regulators have been very successful in cooperating, having completed the whole process from development to licensing at an unprecedented speed. However, we should learn from the experiences, to be able to be even faster when a next pandemic of disease X occurs.
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http://dx.doi.org/10.1016/j.biologicals.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102086PMC
June 2021

SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses.

J Virol 2021 07 12;95(15):e0020321. Epub 2021 Jul 12.

Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.

The majority of SARS-CoV-2 vaccines in use or advanced development are based on the viral spike protein (S) as their immunogen. S is present on virions as prefusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described against both open and closed conformations. The long-term success of vaccination strategies depends upon inducing antibodies that provide long-lasting broad immunity against evolving SARS-CoV-2 strains. Here, we have assessed the results of immunization in a mouse model using an S protein trimer stabilized in the closed state to prevent full exposure of the receptor binding site and therefore interaction with the receptor. We compared this with other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induced a T cell response and long-lived, strongly neutralizing antibody responses against 2019 SARS-CoV-2 and variants of concern P.1 and B.1.351. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralizing responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, immune responses than open spikes and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. We suggest that closed spikes, together with their improved stability and storage properties, may be a valuable component of refined, next-generation vaccines. Vaccines in use against SARS-CoV-2 induce immune responses against the spike protein. There is intense interest in whether the antibody response induced by vaccines will be robust against new variants, as well as in next-generation vaccines for use in previously infected or immunized individuals. We assessed the use as an immunogen of a spike protein engineered to be conformationally stabilized in the closed state where the receptor binding site is occluded. Despite occlusion of the receptor binding site, the spike induces potently neutralizing sera against multiple SARS-CoV-2 variants. Antibodies are raised against a different pattern of epitopes to those induced by other spike constructs, preferring conformational epitopes present in the closed conformation. Closed spikes, or mRNA vaccines based on their sequence, can be a valuable component of next-generation vaccines.
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http://dx.doi.org/10.1128/JVI.00203-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274612PMC
July 2021

A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response.

Vaccines (Basel) 2021 Apr 27;9(5). Epub 2021 Apr 27.

EN-FIST, Centre of Excellence, 1000 Ljubljana, Slovenia.

The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design.
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http://dx.doi.org/10.3390/vaccines9050431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146944PMC
April 2021

A Novel Endoscopic Technique for Biopsy and Tissue Diagnosis for a Paraspinal Thoracic Tumor in a Pediatric Patient: A Case Report.

Int J Spine Surg 2021 Feb 29;14(s4):S66-S70. Epub 2020 Dec 29.

Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

Background: Conventional approaches to the thoracic spine can require extensive tissue dissection, bony disruption, and instability that may warrant the need for instrumentation and fusion. Furthermore, anterior approaches may require the involvement of various surgeons from multiple disciplines to ensure a successful operation and mitigate complications. Currently, available minimally invasive approaches still require bony removal and usually rely heavily on computed tomography (CT)-guided imaging without direct gross visualization. Endoscopic spinal procedures have provided an ultra-minimally invasive alternative to access many areas in and around the spinal column.

Methods: We present a 12-year-old boy with a right-sided 2.0 × 3.2-cm paravertebral lesion at the level of T5. The patient successfully underwent an endoscopic approach to the lesion with minimal tissue and bony disruption for tissue diagnosis and tumor resection.

Results: At initial and 6-month follow-up, the patient remained asymptomatic and without issues.

Conclusions: We demonstrate here the feasibility and suggest the safety of a posterior ultra-minimally invasive endoscopic spinal approach to obtain a tissue biopsy of an incidentally found ventrolateral paraspinal tumor in the thoracic region in a pediatric patient. This minimal approach can prove to achieve similar results as other approaches that may otherwise necessitate more extensive or transthoracic procedures.
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http://dx.doi.org/10.14444/7167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888196PMC
February 2021

Serum neurofilament light chain (sNfL) values in a large cross-sectional population of children with asymptomatic to moderate COVID-19.

J Neurol 2021 Nov 23;268(11):3969-3974. Epub 2021 Apr 23.

University Children's Hospital Regensburg (KUNO), Hospital St. Hedwig of the Order of St. John, University of Regensburg, Steinmetzstr. 1-3, 93049, Regensburg, Germany.

Background: Serum neurofilament light chain (sNfL) is an established biomarker of neuro-axonal damage in multiple neurological disorders. Raised sNfL levels have been reported in adults infected with pandemic coronavirus disease 2019 (COVID-19). Levels in children infected with COVID-19 have not as yet been reported.

Objective: To evaluate whether sNfL is elevated in children contracting COVID-19.

Methods: Between May 22 and July 22, 2020, a network of outpatient pediatricians in Bavaria, Germany, the Coronavirus antibody screening in children from Bavaria study network (CoKiBa), recruited healthy children into a cross-sectional study from two sources: an ongoing prevention program for 1-14 years, and referrals of 1-17 years consulting a pediatrician for possible infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We determined sNfL levels by single molecule array immunoassay and SARS-CoV-2 antibody status by two independent quantitative methods.

Results: Of the 2652 included children, 148 (5.6%) were SARS-CoV-2 antibody positive with asymptomatic to moderate COVID-19 infection. Neurological symptoms-headache, dizziness, muscle aches, or loss of smell and taste-were present in 47/148 cases (31.8%). Mean sNfL levels were 5.5 pg/ml (SD 2.9) in the total cohort, 5.1 (SD 2.1) pg/ml in the children with SARS-CoV-2 antibodies, and 5.5 (SD 3.0) pg/ml in those without. Multivariate regression analysis revealed age-but neither antibody status, antibody levels, nor clinical severity-as an independent predictor of sNfL. Follow-up of children with pediatric multisystem inflammatory syndrome (n = 14) showed no association with sNfL.

Conclusions: In this population study, children with asymptomatic to moderate COVID-19 showed no neurochemical evidence of neuronal damage.
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http://dx.doi.org/10.1007/s00415-021-10554-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064423PMC
November 2021

Regulatory concepts to guide and promote the accelerated but safe clinical development and licensure of COVID-19 vaccines in Europe.

Allergy 2021 Apr 22. Epub 2021 Apr 22.

Department of Virology, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.

The ongoing COVID-19 pandemic caused by the SARS-CoV-2 coronavirus has affected the health of tens of millions of people worldwide. In particular, in elderly and frail individuals the infection can lead to severe disease and even fatal outcomes. Although the pandemic is primarily a human health crisis its consequences are much broader with a tremendous impact on global economics and social systems. Vaccines are considered the most powerful measure to fight the pandemic and protect people from COVID-19. Based on the concerted activities of scientists, manufacturers and regulators, the urgent need for effective countermeasures has provoked the development and licensure of novel COVID-19 vaccines in an unprecedentedly fast and flexible manner within <1 year. To ensure the safety and efficacy of these novel vaccines during the clinical development and the routine use in post-licensure vaccination campaigns existing regulatory requirements and procedures had to be wisely and carefully adapted to allow for an expedited evaluation without compromising the thoroughness of the regulatory and scientific assessment. In this review, we describe the regulatory procedures, concepts and requirements applied to guide and promote the highly accelerated development and licensure of safe and efficacious COVID-19 vaccines in Europe.
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http://dx.doi.org/10.1111/all.14868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251031PMC
April 2021

Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation.

Diagnostics (Basel) 2021 Feb 15;11(2). Epub 2021 Feb 15.

Department of Internal Medicine III, Hematology and Oncology, University Medical Center Regensburg, 93053 Regensburg, Germany.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recipients using a standardized IFN-γ ELISpot assay. Paired qualitative test results showed an overall 74.4% concordance. Discordant results were mainly due to low-response tests, with one exception. One patient with early CMV reactivation and graft-versus-host disease, sustained CMV DNAemia and high CD8 counts showed successive negative protein-based ELISpot results but a high and sustained response to IE-1 peptides. Our results suggest that the response to exogenous proteins, which involves their uptake and processing by antigen-presenting cells, more closely reflects the physiological response to CMV infection, while the response to exogenous peptides may lead to artificial in vitro T-cell responses, especially in strongly immunosuppressed patients.
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http://dx.doi.org/10.3390/diagnostics11020312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919014PMC
February 2021

Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation.

Blood 2021 07;138(1):34-43

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Decreased cytomegalovirus (CMV)-specific immunity after hematopoietic cell transplantation (HCT) is associated with late CMV reactivation and increased mortality. Whether letermovir prophylaxis-associated reduction in viral exposure influences CMV-specific immune reconstitution is unknown. In a prospective cohort of allogeneic HCT recipients who received letermovir, we compared polyfunctional CMV-specific T-cell responses to those of controls who received PCR-guided preemptive therapy before the introduction of letermovir. Thirteen-color flow cytometry was used to assess T-cell responses at 3 months after HCT following stimulation with CMV immediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) antigens. Polyfunctionality was characterized by combinatorial polyfunctionality analysis of antigen-specific T-cell subsets. Use of letermovir and reduction of viral exposure were assessed for their association with CMV-specific T-cell immunity. Polyfunctional T-cell responses to IE-1 and pp65 were decreased in letermovir recipients and remained diminished after adjustment for donor CMV serostatus, absolute lymphocyte count, and steroid use. Among letermovir recipients, greater peak CMV DNAemia and increased viral shedding were associated with stronger CD8+ responses to pp65, whereas the CMV shedding rate was associated with greater CD4+ responses to IE-1. In summary, our study provided initial evidence that letermovir may delay CMV-specific cellular reconstitution, possibly related to decreased CMV antigen exposure. Evaluating T-cell polyfunctionality may identify patients at risk for late CMV infection after HCT.
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http://dx.doi.org/10.1182/blood.2020009396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493975PMC
July 2021

Full endoscopic surgery for thoracic pathology: an assessment of supportive evidence.

EFORT Open Rev 2021 Jan 4;6(1):50-60. Epub 2021 Jan 4.

The Royal College of Surgeons of Edinburgh, Edinburgh, UK.

In the last five years, surgeons have applied endoscopic transforaminal surgical techniques mastered in the lumbar spine to the treatment of thoracic pathology.The aim of this systematic review was to collate the available literature to determine the place and efficacy of full endoscopic approaches used in the treatment of thoracic disc prolapse and stenosis.An electronic literature search of PubMed, Embase, the Cochrane database and Google Scholar was performed as suggested by the Preferred Reporting Items for Systematic Review and Meta-analysis statements. Included were any full-text articles referring to full endoscopic thoracic surgical procedures in any language.We identified 17 patient series, one cohort study and 13 case reports with single or of up to three patients.Although the majority included disc pathology, 11 papers related cord compression in a proportion of cases to ossification of the ligamentum flavum or posterior longitudinal ligament. Two studies described the treatment of discitis and one reported the use of endoscopy for tumour resection.Where reported, excellent or good outcomes were achieved for full endoscopic procedures in a mean of 81% of patients (range 46-100%) with a complication rate of 8% (range 0-15%), comparing favourably with rates reported after open discectomy (anterior, posterolateral and thoracoscopic) or by endoscopic tubular assisted approaches. Twenty-one of the 31 author groups reported use of local anaesthesia plus sedation rather than general anaesthesia, providing 'self-neuromonitoring' by allowing patients to respond to cord and/or nerve stimuli. Cite this article: 2021;6:50-60. DOI: 10.1302/2058-5241.6.200080.
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http://dx.doi.org/10.1302/2058-5241.6.200080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845567PMC
January 2021

Manufacturing of convalescent plasma of COVID-19 patients: Aspects of quality.

PLoS One 2020 22;15(12):e0243967. Epub 2020 Dec 22.

Institute of Clinical Chemistry and Laboratory Medicine, Transfusion Medicine, University Hospital Regensburg, Regensburg, Germany.

The ongoing coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019. Convalescent plasma represents a promising COVID-19 treatment. Here, we report on the manufacturing of a plasma-based product containing antibodies specific to SARS-CoV-2 obtained from recently recovered COVID-19 patients. Convalescent plasma donors were screened as follows: 1) previously confirmed SARS-CoV-2 infection (by real-time PCR (RT-PCR)); 2) a subsequent negative PCR test followed by a 2-week waiting period; 3) an additional negative PCR test prior to plasmapheresis; and 4) confirmation of the presence of SARS-CoV-2 specific antibodies. Convalescent plasma was stored fresh (2-6°C) for up to 5 days or frozen (-30°C) for long-term storage. Donor peripheral blood and final plasma product were assayed for binding antibodies targeting the SARS-CoV-2 S-protein receptor-binding domain (RBD) and their titers measured by an enzyme-linked immunosorbent assay (ELISA). We performed 72 plasmaphereses resulting in 248 final products. Convalescent plasma contained an RBD-specific antibody titer (IgG) ranging from 1:100 to 1:3200 (median 1:800). The titer was congruent to the titer of the blood (n = 34) before collection (1:100-1:6400, median 1:800). Levels of IL-8 and LBP of donors were slightly increased. Therapeutic products derived from a human origin must undergo rigorous testing to ensure uniform quality and patient safety. Whilst previous publications recommended RBD-specific binding antibody titers of ≥ 1:320, we selected a minimum titer of 1:800 in order to maximize antibody delivery. Production of highly standardized convalescent plasma was safe, feasible and was readily implemented in the treatment of severely ill COVID-19 patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243967PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755199PMC
January 2021

Four Complications Associated with Lateral and Oblique Fusion Treatable with Endoscopic Spine Surgery: Technical Note and Case Series.

Pain Physician 2020 11;23(6):E665-E671

Department of Neurosurgery, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI.

Background: The lateral fusion procedure is a newer minimally invasive approach to indirectly decompressing and fusing a lumbar motion segment. As with many new procedures, new thoughtful approaches to recognizing and treating the complications of these procedures need to be developed.

Objectives: Here we describe our experience with transforaminal endoscopic decompression for complications of lateral and oblique lumbar fusion.

Study Design: Retrospective case review.

Setting: This was a multicenter study that took place in an academic hospital, community hospital, and ambulatory surgery center.

Methods: An endoscopic treatment technique for 4 types of complications associated with lateral and oblique fusion is presented. We retrospectively reviewed cases at 3 centers in 2 countries of patients who underwent transforaminal endoscopic surgery for the treatment of lateral fusion complications in a 4-year period with a minimum follow-up of 1 year.

Results: A preliminary series of 4 patients with an average age of 74.8 years (range, 69-82 years) who underwent transforaminal endoscopic procedures at the level of their lateral and oblique lumbar fusions between 2014 and 2018 is presented. Disc herniations, heterotopic bone formation, endplate fracture, and nerve root impingement by the interbody device were all treated endoscopically.

Limitations: Small case series evaluated retrospectively with 1-year follow-up.

Conclusions: Transforaminal endoscopic surgery is a useful minimally invasive surgical technique to treat several complications associated with lateral and oblique lumbar interbody fusion procedures.
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November 2020

Expectations Regarding Dental Practice: A Cross-Sectional Survey of European Dental Students.

Int J Environ Res Public Health 2020 10 6;17(19). Epub 2020 Oct 6.

Department of Restorative, Preventive and Pediatric Dentistry, School of Dental Medicine, University of Bern, CH-3010 Bern, Switzerland.

Obtaining information on expectations among dental students regarding their career planning was the main purpose of this observational online survey. The questionnaire was designed with 18 items in five different languages: English, French, German, Italian and Spanish. Data were collected on nationality, age, sex, country of residence, university attended, semester, expected year of graduation and expectations about future career. More than 3000 participants ( = 3851, 2863 females 74.34% and 988 males 25.66% with a sex ratio of 0.35) participated in the survey. Almost one-third (31.29%) of the participants plan to start their own practice at least three years after vocational training, a quarter (25.76%) after three, and only 12.59% after one year. A positive influence of the family in the decision to start a practice was observed in 50.07% of the sample with a statistically significant difference regarding sex ( < 0.01). Almost one-third of the participants did not wish to work in an institution run by private equity or insurance companies, while 21.79% would work in that environment ( < 0.01). European dental students desire mainly to become self-employed and start their own practice. New professional practices also offer them options for their future career that they have not yet decided on or thought about.
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http://dx.doi.org/10.3390/ijerph17197296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579228PMC
October 2020

Silica particles incorporated into PLGA-based in situ-forming implants exploit the dual advantage of sustained release and particulate delivery.

Eur J Pharm Biopharm 2020 Nov 27;156:1-10. Epub 2020 Aug 27.

Department of Pharmaceutical Technology, University Regensburg, Universitaetsstrasse 31, 93040 Regensburg, Germany. Electronic address:

Poly (lactic-co-glycolic acid) (PLGA) in situ-forming implants are well-established drug delivery systems for controlled drug release over weeks up to months. To prevent initial burst release, which is still a major issue associated with PLGA-based implants, drugs attached to particulate carriers have been encapsulated. Unfortunately, former studies only investigated the resulting release of the soluble drugs and hence missed the potential offered by particulate drug release. In this study, we developed a system capable of releasing functional drug-carrying particles over a prolonged time. First, we evaluated the feasibility of our approach by encapsulating silica particles of different sizes (500 nm and 1 μm) and surface properties (OH or NH groups) into in situ-forming PLGA implants. In this way, we achieved sustained release of particles over periods ranging from 30 to 70 days. OH-carrying particles were released much more quickly when compared to NH-modified particles. We demonstrated that the underlying release mechanisms involve size-dependent diffusion and polymer-particle interactions. Second, particles that carried covalently-attached ovalbumin (OVA) on their surfaces were incorporated into the implant. We demonstrated that OVA was released in association with the particles as functional entities over a period of 30 days. The released particle-drug conjugates maintained their colloidal stability and were efficiently taken up by antigen presenting cells. This system consisting of particles incorporated into PLGA-based in situ-forming implants offers the dual advantage of sustained and particulate release of drugs as a functional unit and has potential for future use in many applications, particularly in single-dose vaccines.
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http://dx.doi.org/10.1016/j.ejpb.2020.08.020DOI Listing
November 2020

A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization.

Infection 2021 Feb 21;49(1):75-82. Epub 2020 Aug 21.

Department for Infection Control and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany.

Objective: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels.

Methods: In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated.

Results: The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum.

Conclusions: With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.
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http://dx.doi.org/10.1007/s15010-020-01503-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441844PMC
February 2021

Indications and Contraindications of Full-Endoscopic Interlaminar Lumbar Decompression.

World Neurosurg 2021 01 15;145:657-662. Epub 2020 Aug 15.

Endoscopic Spine Experts, Joimax GmbH, Karlsruhe, Germany.

Background: Spinal stenosis is a common disease with an increasing incidence. Narrowing of the spinal canal is caused by bone and soft tissue degeneration, such as osteophyte formation, facet and ligamentum flavum hypertrophy, and disc herniation. Various surgical techniques have been used to treat spinal canal stenosis, including open, tubular, microsurgical decompression, and fusion surgery. This article presents the technique for full-endoscopic interlaminar bilateral decompression of the lumbar spine.

Methods: Surgical approach, anatomy, pathology, indications, contraindications, and surgical equipment are described.

Results: With well-chosen endoscopic equipment, surgical time can be reduced with minimal collateral damage. Clear advantages of full-endoscopic decompression over open or other minimally invasive surgery methods are demonstrated in many clinical studies. The endoscopic technique has been shown to be effective in spinal canal decompression with good to excellent clinical results. The interlaminar endoscopic approach minimizes iatrogenic injury to the stabilizing anatomic structures while achieving full unilateral and bilateral decompression. A significant improvement in pain and functional outcome scores with low complication rates has been demonstrated.

Conclusions: This technique is safe for lumbar spinal decompression and more minimally invasive than a microendoscopic approach. However, this technique should be performed by surgeons with advanced skills. Endoscopy could become the gold standard for treatment of canal stenosis in the near future.
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http://dx.doi.org/10.1016/j.wneu.2020.08.042DOI Listing
January 2021

Uniportal Endoscopic Lumbar Interbody Fusion.

Neurospine 2020 Jul 31;17(Suppl 1):S120-S128. Epub 2020 Jul 31.

Endoscopic Spine Experts, Joimax GmbH, Karlsruhe, Germany.

The cause of radiculopathy is the compression of the nerve root which can be secondary to sliding of the vertebra and reduced disc height. In some patients, decompression alone does not resolve this problem. We describe the uniportal endoscopic transforaminal lumbar interbody fusion technique. Full-endocopic foraminotomy and discectomy are followed by cage implementation and percutaneous instrumentation. The goal of this surgical method is decompression of nerve roots, segment stabilization, disc height, and sagittal alignment restoration. Uniportal endoscopic facet sparing transforaminal transkambin lumbar interbody fusion is a good surgical option to treat degenerative disc disease, mechanical instability, and spondylolisthesis. This method shows favourable clinical outcomes in selected patients.
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http://dx.doi.org/10.14245/ns.2040130.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410390PMC
July 2020
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