Cross-Reactivity of Zika and Other Flaviviruses in Serological Diagnostics

Zika virus (ZIKV) co-circulates with several closely related flaviviruses which exhibit similar clinical manifestations thus, clinicians rely on molecular and serological techniques for diagnosis. Cross-reactivity of patient specimens to flaviviruses is a significant impediment to serological diagnosis in areas where multiple flaviviruses co-circulate. Furthermore, patient exposure history to any of these viruses could complicate serological response patterns which could result in over and/or underdiagnosis of ZIKV infection. Three strains of ZIKV, dengue serotypes 1-4, West Nile virus, Japanese Encephalitis virus, and Yellow Fever virus were evaluated for neutralizing properties against 3 monoclonal antibodies, 4 ZIKV-naïve patients with flavivirus exposure history, 5 patients with verified ZIKV exposure and unknown flavivirus exposure history, and 5 flavivirus-naive patients with ZIKV-only exposure. Patients naïve for ZIKV exposure effectively neutralized multiple strains of ZIKV. Overall, the prototype ZIKV isolate MR-766 did not behave like the other ZIKV isolated used in this study. MR-766 was neutralized more completely by polyclonal patient serum than recent ZIKV isolates. MR-766 was neutralized better than dengue virus in ZIKV-naïve patients with prior dengue exposure. MR-766 was neutralized significantly less than recent ZIKV isolates when treated with monoclonal antibodies. The data herein show that without RT-PCR, serological diagnosis may not be possible in areas where multiple flaviviruses are endemic.

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Strain-Dependent Activity of Zika Virus and Exposure History in Serological Diagnostics

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5010038 ◽

2020 ◽

Vol 5 (1) ◽

pp. 38

Author(s):

Kelli L. Barr ◽

Erika R. Schwarz ◽

Dhani Prakoso ◽

Kehkashan Imtiaz ◽

Ruiyu Pu ◽

...

Keyword(s):

Zika Virus ◽

Vaccine Development ◽

Cross Reactivity ◽

Serological Diagnosis ◽

Dependent Activity ◽

Exposure History ◽

Simplex Virus ◽

Strain Dependent ◽

Polyclonal Serum ◽

Better Than

Zika virus (ZIKV) circulates as two separate lineages, with significant genetic variability between strains. Strain-dependent activity has been reported for dengue virus, herpes simplex virus and influenza. Strain-dependent activity of subject specimens to a virus could be an impediment to serological diagnosis and vaccine development. In order to determine whether ZIKV exhibits strain-dependent activity when exposed to antibodies, we measured the neutralizing properties of polyclonal serum and three monoclonal antibodies (ZKA185, 753(3)C10, and 4G2) against three strains of ZIKV (MR−766, PRVABC59, and R103454). Here, MR−766 was inhibited almost 60% less by ZKA185 than PRVABC59 and R103454 (p = 0.008). ZKA185 enhanced dengue 4 infection up to 50% (p = 0.0058). PRVABC59 was not inhibited by mAb 753(3)C10 while MR−766 and R103453 were inhibited up to 90% (p = 0.04 and 0.036, respectively). Patient serum, regardless of exposure history, neutralized MR−766 ~30%−40% better than PRVABC56 or R103454 (p = 0.005−0.00007). The most troubling finding was the significant neutralization of MR−766 by patients with no ZIKV exposure. We also evaluated ZIKV antibody cross reactivity with various flaviviruses and found that more patients developed cross-reactive antibodies to Japanese encephalitis virus than the dengue viruses. The data here show that serological diagnosis of ZIKV is complicated and that qualitative neutralization assays cannot discriminate between flaviviruses.

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Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2

10.1101/2020.03.06.980037 ◽

2020 ◽

Cited By ~ 10

Author(s):

Zhiqiang Zheng ◽

Vanessa M. Monteil ◽

Sebastian Maurer-Stroh ◽

Chow Wenn Yew ◽

Carol Leong ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Cell Receptor ◽

Cross Reactivity ◽

Diagnostic Assays ◽

Host Cell Receptor ◽

High Sequence Conservation ◽

Infected Cells ◽

Novel Coronavirus ◽

Multiple Strains ◽

Human Infections

AbstractThe emergence of a novel coronavirus, SARS-CoV-2, at the end of 2019 has resulted in widespread human infections across the globe. While genetically distinct from SARS-CoV, the etiological agent that caused an outbreak of severe acute respiratory syndrome (SARS) in 2003, both coronaviruses exhibit receptor binding domain (RBD) conservation and utilize the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), for virus entry. Therefore, it will be important to test the cross-reactivity of antibodies that have been previously generated against the surface spike (S) glycoprotein of SARS-CoV in order to aid research on the newly emerged SARS-CoV-2. Here, we show that an immunogenic domain in the S2 subunit of SARS-CoV S is highly conserved in multiple strains of SARS-CoV-2. Consistently, four murine monoclonal antibodies (mAbs) raised against this immunogenic SARS-CoV fragment were able to recognise the S protein of SARS-CoV-2 expressed in a mammalian cell line. Importantly, one of them (mAb 1A9) was demonstrated to detect S in SARS-CoV-2-infected cells. To our knowledge, this is the first study showing that mAbs targeting the S2 domain of SARS-CoV can cross-react with SARS-CoV-2 and this observation is consistent with the high sequence conservation in the S2 subunit. These cross-reactive mAbs may serve as tools useful for SARS-CoV-2 research as well as for the development of diagnostic assays for its associated coronavirus disease COVID-19.

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New data on the pathogenicity of genotype of Rickettsia sibirica subspecies BJ-90

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40815 ◽

2014 ◽

Vol 19 (5) ◽

pp. 10-13

Author(s):

N. V Rudakov ◽

S. N Shpynov ◽

T. A Reshetnikova ◽

N. A Penevskaya ◽

N. V Abramova ◽

...

Keyword(s):

Cell Cultures ◽

Guinea Pigs ◽

Clinical Manifestations ◽

Cross Reactivity ◽

Serological Diagnosis ◽

Chick Embryos ◽

Primorye Region ◽

Rickettsia Sibirica

New data about pathogenicity of Rickettsia sibirica subspecies BJ-90 were obtained. Rickettsial strains of this subspecies from the Primorye region were pathogenic for guinea pigs and chick embryos, multiplied in cell cultures Vero E6. Antibodies against Rickettsia sibirica subspecies BJ-90 in ELISA were detected in the Omsk region in patients with clinical manifestations after bites of ticks. Analysis of available data indicates to the likely pathogenicity of this genotype for human. Due to the low cross reactivity of R. sibirica subsp. BJ-90 and R. sibirica subsp. sibirica in combined foci serological diagnosis of tick-borne rickettsioses in ELISA should be carried out with antigens of both subspecies of Rickettsia sibirica.

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КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ ПИЩЕВЫХ АЛЛЕРГЕНОВ ЖИВОТНОГО ПРОИСХОЖДЕНИЯ

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/raj.2019.1-1.53221 ◽

2019 ◽

Author(s):

A.N. Pampura ◽

E.E. Varlamov

Keyword(s):

Clinical Manifestations ◽

Red Meat ◽

Cross Reactivity ◽

Allergic Reactions ◽

Essential Nutrients ◽

Animal Products ◽

Food Animal ◽

Mammalian Meat

Продукты животного происхождения обладают наиболее сбалансированным комплексом необходимых нутриентов, поэтому их включение в пищевой рацион оправданно в различные возрастные периоды. Клинические проявления аллергии к данным продуктам крайне разнообразны. Одним из ключевых аспектов обозначенной проблемы является диагностика и оценка вероятности развития перекрестной реактивности. К пищевым продуктам животного происхождения, наиболее часто индуцирующим симптомы, относятся коровье молоко, куриное яйцо, рыба, моллюски, ракообразные, мясо млекопитающих. В представленной статье изложены данные об основных классах пищевых аллергенов животного происхождения, индуцирующих развитие перекрестных аллергических реакций. Описаны синдромы, связанные с перекрестной реактивностью: птица-яйцо , кошка-свинина , рыба-курица и -Gal-синдром/ синдром красного мяса .Animal foods products contain the most balanced complex of essential nutrients. The clinical manifestations of allergy to these products are varied. Key aspect of this problem is diagnostics and assessment of cross-reactivity. The food animal products that more often induce symptoms include cows milk, hens egg, fish, mollusks, crustaceans, mammalian meat. Data on the main classes of food animal allergens inducing the development of cross-allergic reactions as well as syndromes associated with cross-reactivity like bird-egg , cat-pork , fish-chicken and a-Gal-syndrome/ red meat syndrome are described in this article.

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SURG-22. CUSHING’S DISEASE: A DIFFICULT TO TREAT NEURO-ONCOLOGICAL CONDITION

Neuro-Oncology ◽

10.1093/neuonc/noz175.1022 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi244-vi244

Author(s):

Santanu Bora ◽

Ashish Suri

Keyword(s):

Cortisol Level ◽

Remission Rate ◽

Univariate Analysis ◽

Clinical Manifestations ◽

Plasma Cortisol Level ◽

Cushing Disease ◽

Factors Affecting ◽

Microscopic Surgery ◽

Acth Secreting ◽

Better Than

Abstract BACKGROUND Cushing disease (CD) comprises a spectrum of clinical manifestations secondary to hypercortisolism due to ACTH-secreting pituitary adenoma. Transsphenoidal adenomectomy remains the standard treatment. Because of the significant rate of recurrence or persistence of CD, it is of interest to determine factors that may correlate with long-term outcomes following surgical intervention. OBJECTIVE The objective of our study is to determine the remission rate after surgery with special emphasis on factors affecting remission. METHODS Data of all patients undergoing surgery for CD from 2009 to 2017 was analyzed retrospectively. Transphenoidal resection was the preferred treatment with a recent trend in favor of endonasal endoscopic skull base approach. Post-operative cortisol level of < 2 μg/dL was taken as remission and value between 2 and 5 μg/dL as possible remission. RESULTS 104 patients operated primarily for CD were included for analysis. 47 patients underwent microscopic surgery, 55 endoscopic surgery and two were operated trans-cranially. Remission was achieved in 76.47% of patients. In univariate analysis, factors significantly associated with remission were (1) type of surgery (p=0.01); endoscopy (88.23% remission) better than microscopy (56.6% remission) (2) postoperative day-1 morning cortisol (p=0.004) and; (3) postoperative day-1 morning ACTH (p=0.015). In multivariate analysis, however only postoperative day-1 cortisol was found to be significant as predictor of remission (p=0.02). CONCLUSION Postoperative plasma cortisol level is a strong independent predictor of remission and value less than 10.7µgm/dl can be taken as cut off for predicting remission. Remission provided by endoscopy appears to be significantly better than microscopic approach.

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Development of a Colloidal Gold Immunochromatographic Assay for Duck Enteritis Virus Detection Using Monoclonal Antibodies

Pathogens ◽

10.3390/pathogens10030365 ◽

2021 ◽

Vol 10 (3) ◽

pp. 365

Author(s):

Fengli Liu ◽

Yanxin Cao ◽

Maokai Yan ◽

Mengxu Sun ◽

Qingshui Zhang ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Colloidal Gold ◽

Preventive Intervention ◽

Virus Detection ◽

Cross Reactivity ◽

Duck Enteritis Virus ◽

Detection Sensitivity ◽

Immunochromatographic Assay ◽

Efficient Detection ◽

Enteritis Virus

Duck viral enteritis is a highly contagious and fatal disease of commercial waterfowl flocks. The disease occurs sporadically or epizootically in mainland China due to insufficient vaccinations. Early and rapid diagnosis is important for preventive intervention and the control of epizootic events in clinical settings. In this study, we generated two monoclonal antibodies (MAbs) that specifically recognized the duck enteritis virus (DEV) envelope glycoprotein B and tegument protein UL47, respectively. Using these MAbs, a colloidal gold-based immunochromatographic assay (ICA) was developed for the efficient detection of DEV antigens within 15 min. Our results showed that the detection limit of the developed ICA strip was 2.52 × 103 TCID50/mL for the virus infected cell culture suspension with no cross-reactivity with other pathogenic viruses commonly encountered in commercially raised waterfowl. Using samples from experimentally infected ducks, we demonstrated that the ICA detected the virus in cloacal swab samples on day three post-infection, demonstrating an 80% concordance with the PCR. For tissue homogenates from ducks succumbing to infection, the detection sensitivity was 100%. The efficient and specific detection by this ICA test provides a valuable, convenient, easy to use and rapid diagnostic tool for DVE under both laboratory and field conditions.

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Monoclonal antibodies to bovine UDP-galactosyltransferase. Characterization, cross-reactivity, and utilization as structural probes.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)57498-1 ◽

1986 ◽

Vol 261 (17) ◽

pp. 7975-7981

Author(s):

J T Ulrich ◽

J R Schenck ◽

H G Rittenhouse ◽

N L Shaper ◽

J H Shaper

Keyword(s):

Monoclonal Antibodies ◽

Cross Reactivity ◽

Structural Probes

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Clinical outcomes of syphilis in HIV-negative and HIV-positive MSM: occurrence of repeat syphilis episodes and non-treponemal serology responses

Sexually Transmitted Infections ◽

10.1136/sextrans-2020-054887 ◽

2021 ◽

pp. sextrans-2020-054887

Author(s):

Silvia Achia Nieuwenburg ◽

Ricardo Jamie Sprenger ◽

Maarten Franciscus Schim van der Loeff ◽

Henry John Christiaan de Vries

Keyword(s):

Hiv Infection ◽

Controlled Trial ◽

Clinical Manifestations ◽

Response To Treatment ◽

Disease Stage ◽

Hiv Positive ◽

Sexual Risk Behaviour ◽

Serological Response ◽

History Of ◽

Hiv Negative

ObjectivesHIV-positive men who have sex with men (MSM) may be at a higher risk of repeat syphilis, have different clinical manifestations and have a different serological response to treatment compared with HIV-negative MSM. The objective of this study was to assess whether HIV-negative and HIV-positive MSM with infectious syphilis (primary, secondary or early latent) differed in history of previous syphilis episodes, disease stage and non-treponemal titre of initial and repeat episodes, and the titre response 6 and 12 months after treatment. Furthermore, determinants associated with an inadequate titre response after treatment were explored.MethodsThis retrospective analysis used data of five longitudinal studies (four cohorts; one randomised controlled trial) conducted at the STI clinic in Amsterdam, the Netherlands. Participants were tested for syphilis and completed questionnaires on sexual risk behaviour every 3–6 months. We included data of participants with ≥1 syphilis diagnosis in 2014–2019. Pearson’s χ² test was used to compare HIV-negative and HIV-positive MSM in occurrence of previous syphilis episodes, disease stage of initial and repeat syphilis episode and non-treponemal titre treatment responses.ResultsWe included 355 participants with total 459 syphilis episodes. HIV-positive MSM were more likely to have a history of previous syphilis episodes compared with HIV-negative MSM (68/90 (75.6%) vs 96/265 (36.2%); p<0.001). Moreover, HIV-positive MSM with repeat syphilis were less often diagnosed with primary syphilis (7/73 (9.6%) vs 36/126 (28.6%)) and more often diagnosed with secondary syphilis (16/73 (21.9%) vs 17/126 (13.5%)) and early latent syphilis (50/73 (68.5%) vs 73/126 (57.9%)) (p=0.005). While not significantly different at 12 months, HIV-negative MSM were more likely to have an adequate titre response after 6 months compared with HIV-positive MSM (138/143 (96.5%) vs 66/74 (89.2%); p=0.032).ConclusionsIn repeat syphilis, HIV infection is associated with advanced syphilis stages and with higher non-treponemal titres. HIV infection affects the serological outcome after treatment, as an adequate titre response was observed earlier in HIV-negative MSM.

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Screening and development of monoclonal antibodies for identification of ferret T follicular helper cells

Scientific Reports ◽

10.1038/s41598-021-81389-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wenbo Jiang ◽

Julius Wong ◽

Hyon-Xhi Tan ◽

Hannah G. Kelly ◽

Paul G. Whitney ◽

...

Keyword(s):

Animal Model ◽

Monoclonal Antibodies ◽

Lymph Node ◽

Cross Reactivity ◽

Tfh Cells ◽

Follicular Helper ◽

Lymph Node Cells ◽

Human Viruses ◽

Humoral Responses ◽

Murine Monoclonal Antibodies

AbstractThe ferret is a key animal model for investigating the pathogenicity and transmissibility of important human viruses, and for the pre‐clinical assessment of vaccines. However, relatively little is known about the ferret immune system, due in part to a paucity of ferret‐reactive reagents. In particular, T follicular helper (Tfh) cells are critical in the generation of effective humoral responses in humans, mice and other animal models but to date it has not been possible to identify Tfh in ferrets. Here, we describe the screening and development of ferret-reactive BCL6, CXCR5 and PD-1 monoclonal antibodies. We found two commercial anti-BCL6 antibodies (clone K112-91 and clone IG191E/A8) had cross-reactivity with lymph node cells from influenza-infected ferrets. We next developed two murine monoclonal antibodies against ferret CXCR5 (clone feX5-C05) and PD-1 (clone fePD-CL1) using a single B cell PCR-based method. We were able to clearly identify Tfh cells in lymph nodes from influenza infected ferrets using these antibodies. The development of ferret Tfh marker antibodies and the identification of ferret Tfh cells will assist the evaluation of vaccine-induced Tfh responses in the ferret model and the design of novel vaccines against the infection of influenza and other viruses, including SARS-CoV2.

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