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

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.

Cross-Reactivity of Zika and Other Flaviviruses in Serological Diagnostics

2019 ◽  
Author(s):  
Kelli L. Barr ◽  
Erika R. Schwarz ◽  
Dhani Prakoso ◽  
Kehkashan Imtiaz ◽  
Ruiyu Pu ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Yellow Fever Virus ◽  
Clinical Manifestations ◽  
Cross Reactivity ◽  
Serological Diagnosis ◽  
Serological Response ◽  
Response Patterns ◽  
Exposure History ◽  
Multiple Strains ◽  
Better Than

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.

scholarly journals Development of vaccines against the sexually transmitted infections gonorrhoea, syphilis, Chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus

2020 ◽  
Vol 8 ◽  
pp. 251513552092388
Author(s):  
Edwin David G. McIntosh
Keyword(s):  
Human Immunodeficiency Virus ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sexually Transmitted Infections ◽  
Zika Virus ◽  
Vaccine Development ◽  
Current Status ◽  
Sexually Transmitted ◽  
Immunodeficiency Virus ◽  
Simplex Virus

The success in preventing hepatitis B virus and human papillomavirus infections by means of vaccination paves the way for the development of other vaccines to prevent sexually transmitted infections (STIs) such as gonorrhoea, syphilis, chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus. The current status of vaccine development for these infections will be explored in this review. The general principles for success include the need for prevention of latency, persistence and repeat infections. A reduction in transmission of STIs would reduce the global burden of disease. Therapeutic activity of vaccines against STIs would be advantageous over preventative activity alone, and prevention of congenital and neonatal infections would be an added benefit. There would be an added value in the prevention of long-term consequences of STIs. It may be possible to re-purpose ‘old’ vaccines for new indications. One of the major challenges is the determination of the target populations for STI vaccination.

scholarly journals Functional activity of antisera against recombinant Zika virus envelope protein subunits expressed in Escherichia coli

2019 ◽  
Author(s):  
Hong-Yun Tham ◽  
Man Kwan Ooi ◽  
Vinod RMT Balasubramaniam ◽  
Sharifah Syed Hassan ◽  
Hong-Wai Tham
Keyword(s):  
Zika Virus ◽  
Envelope Protein ◽  
Mammalian Cells ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Cross Reactivity ◽  
Virus Envelope ◽  
Humoral And Cellular Immunity ◽  
Progressive Development

AbstractThe global Zika virus (ZIKV) outbreak across continents has been drawing research attentions to researchers and healthcare professionals. It highlights the urgent development of ZIKV vaccines that offer rapid, precise and specific protection to those living in the high-risk regions - the tropical and subtropical regions. As a public health priority, there is a progressive development in the discovery of vaccine candidates and design in recent years. Many efforts have been placed in the in vitro development of ZIKV subunits as the vaccine candidate in various protein expression systems, including bacteria, yeast, plant cells, insect cells and mammalian cells. However, due to the lack of knowledge on humoral and cellular immune responses against virus vaccines, a commercialised vaccine against Dengue virus (DENV) has been suspended due to a health scare in Philippines. Moreover, the closely-related DENV and ZIKV has indicated serological cross-reactivity between both viruses. This has led to greater attentions to precautions needed during the design of ZIKV and DENV vaccines. In this study, we pre-selected, synthesised and expressed the domain III of ZIKV envelope protein (namely rEDIII) based on a previously-established report (GenBank: AMC13911.1). The characteristics of purified ZIKV rEDIII was tested using SDS-PAGE, Western blotting and LC-MS/MS. Since the ZIKV rEDIII has been well reported as a potential protein candidate in ZIKV vaccine development, we assessed the possible outcome of preexisting immunity against the rEDIII proteins by conducting dot-blotting assays using mice antisera pre-immunised with ZIKV particles (ZIKV strain: MRS_OPY_Martinique_PaRi_2015, GenBank: KU647676) . Surprisingly, the antisera was able to recognise the rEDIII of a different ZIKV strain (GenBank: AMC13911.1). Despite its great antigenicity in eliciting humoral and cellular immunity against ZIKV infection, our finding calls for greater attention to evaluate the details of ZIKV rEDIII as a stand-alone vaccine candidate.

scholarly journals Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity

Science ◽  
2020 ◽  
Vol 370 (6520) ◽  
pp. eabd4250 ◽  
Author(s):  
Ellen Shrock ◽  
Eric Fujimura ◽  
Tomasz Kula ◽  
Richard T. Timms ◽  
I-Hsiu Lee ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Herpes Simplex Virus 1 ◽  
Viral Epitope ◽  
Machine Learning Model ◽  
Exposure History ◽  
Demographic Covariates ◽  
Simplex Virus ◽  
Humoral Responses

Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 coronavirus disease 2019 (COVID-19) patients and 190 pre–COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Preexisting antibodies in controls recognized SARS-CoV-2 ORF1, whereas only COVID-19 patient antibodies primarily recognized spike protein and nucleoprotein. A machine learning model trained on VirScan data predicted SARS-CoV-2 exposure history with 99% sensitivity and 98% specificity; a rapid Luminex-based diagnostic was developed from the most discriminatory SARS-CoV-2 peptides. Individuals with more severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, weaker antibody responses to prior infections, and higher incidence of cytomegalovirus and herpes simplex virus 1, possibly influenced by demographic covariates. Among hospitalized patients, males produce stronger SARS-CoV-2 antibody responses than females.

scholarly journals Diagnosis of Zika Virus Infection by Peptide Array and Enzyme-Linked Immunosorbent Assay

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Nischay Mishra ◽  
Adrian Caciula ◽  
Adam Price ◽  
Riddhi Thakkar ◽  
James Ng ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Immunosorbent Assay ◽  
Zika Virus ◽  
Natural Infection ◽  
Cross Reactivity ◽  
High Density ◽  
Serological Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Molecular Testing ◽  
West Nile

ABSTRACTZika virus (ZIKV) is implicated in fetal stillbirth, microcephaly, intracranial calcifications, and ocular anomalies following vertical transmission from infected mothers. In adults, infection may trigger autoimmune inflammatory polyneuropathy. Transmission most commonly follows the bite of infectedAedesmosquitoes but may also occur through sexual intercourse or receipt of blood products. Definitive diagnosis through detection of viral RNA is possible in serum or plasma within 10 days of disease onset, in whole blood within 3 weeks of onset, and in semen for up to 3 months. Serological diagnosis is nonetheless critical because few patients have access to molecular diagnostics during the acute phase of infection and infection may be associated with only mild or inapparent disease that does not prompt molecular testing. Serological diagnosis is confounded by cross-reactivity of immune sera with other flaviviruses endemic in the areas where ZIKV has recently emerged. Accordingly, we built a high-density microarray comprising nonredundant 12-mer peptides that tile, with one-residue overlap, the proteomes of Zika, dengue, yellow fever, West Nile, Ilheus, Oropouche, and chikungunya viruses. Serological analysis enabled discovery of a ZIKV NS2B 20-residue peptide that had high sensitivity (96.0%) and specificity (95.9%) versus natural infection with or vaccination against dengue, chikungunya, yellow fever, West Nile, tick-borne encephalitis, or Japanese encephalitis virus in a microarray assay and an enzyme-linked immunosorbent assay (ELISA) of early-convalescent-phase sera (2 to 3 weeks after onset of symptomatic infection).IMPORTANCEThe emergence of Zika virus (ZIKV) as a teratogen is a profound challenge to global public health. Molecular diagnosis of infection is straightforward during the 3-week period when patients are viremic. However, serological diagnosis thereafter of historical exposure has been confounded by cross-reactivity. Using high-density peptide arrays that tile the proteomes of a selection of flaviviruses to identify a ZIKV-specific peptide, we established two assays that enable sensitive and specific diagnosis of exposure to ZIKV. These assays may be useful in guiding clinical management of mothers at risk for potential exposure to ZIKV and enable insights into the epidemiology of ZIKV infections.

scholarly journals Accuracy of the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay from the Centers for Disease Control and Prevention (CDC Zika MAC-ELISA) for Diagnosis of Zika Virus Infection

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 835
Author(s):  
Moyra Machado Portilho ◽  
Laise de Moraes ◽  
Mariana Kikuti ◽  
Leile Camila Jacob Nascimento ◽  
Mitermayer Galvão Reis ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Zika Virus ◽  
Cross Reactivity ◽  
Serological Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Rt Pcr ◽  
Zikv Infection ◽  
Igm Antibody ◽  
Convalescent Phase ◽  
Antibody Capture

Serological diagnosis of Zika virus (ZIKV) infection is challenging because of antigenic cross-reactivity with dengue virus (DENV). This study evaluated the accuracy of the Zika IgM antibody capture enzyme-linked immunosorbent assay (CDC Zika IgM MAC-ELISA) in differentiating between ZIKV and DENV infections. To determine sensitivity, we used acute- and convalescent-phase sera from 21 patients with RT-PCR-confirmed ZIKV infection. To determine specificity, we used acute- and convalescent-phase sera from 60 RT-PCR-confirmed dengue cases and sera from 23 blood donors. During the acute-phase of the illness, the assay presented a sensitivity of 12.5% (2/16) for samples collected 0–4 days post symptoms onset (DPSO), and of 75.0% (3/4) for samples collected 5–9 DPSO. During the convalescent-phase of the illness, the test sensitivity was 90.9% (10/11), 100% (2/2), and 0% (0/2) for samples obtained 12–102, 258–260, and 722–727 DPSO, respectively. Specificity for acute- and convalescent-phase samples from RT-PCR-confirmed dengue cases was 100% and 93.2%, respectively. Specificity for blood donor samples was 100%. The assay is an accurate method for Zika serological diagnosis and proved to be reliable for use during surveillance and outbreak investigations in settings where ZIKV and DENV cocirculate.

scholarly journals Development of vaccines against gonorrhoea, syphilis, chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus

2019 ◽  
Vol 21 (4) ◽  
pp. 253-260
Author(s):  
E. David G. McIntosh
Keyword(s):  
Human Immunodeficiency Virus ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Zika Virus ◽  
Vaccine Development ◽  
Current Status ◽  
Sexually Transmitted ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Simplex Virus

The success in preventing hepatitis B virus and human papillomavirus infections by means of vaccination paves the way for the development of other vaccines to prevent sexually transmitted infections (STIs) such as gonorrhoea, syphilis, chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus. The current status of vaccine development for these infections will be explored in this review.

scholarly journals A Label and Probe-Free Zika Virus Immunosensor Prussian Blue@carbon Nanotube-Based for Amperometric Detection of the NS2B Protein

Biosensors ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 157
Author(s):  
Bárbara V. M. Silva ◽  
Marli T. Cordeiro ◽  
Marco A. B. Rodrigues ◽  
Ernesto T. A. Marques ◽  
Rosa F. Dutra
Keyword(s):  
Carbon Nanotube ◽  
Prussian Blue ◽  
Zika Virus ◽  
Point Of Care ◽  
Amperometric Detection ◽  
Cross Reactivity ◽  
Structural Protein ◽  
Serum Samples ◽  
Polypyrrole Composite ◽  
Congenital Disabilities

Zika virus (ZIKV) is a mosquito-borne infection, predominant in tropical and subtropical regions causing international concern due to the ZIKV disease having been associated with congenital disabilities, especially microcephaly and other congenital abnormalities in the fetus and newborns. Development of strategies that minimize the devastating impact by monitoring and preventing ZIKV transmission through sexual intercourse, especially in pregnant women, since no vaccine is yet available for the prevention or treatment, is critically important. ZIKV infection is generally asymptomatic and cross-reactivity with dengue virus (DENV) is a global concern. An innovative screen-printed electrode (SPE) was developed for amperometric detection of the non-structural protein (NS2B) of ZIKV by exploring the intrinsic redox catalytic activity of Prussian blue (PB), incorporated into a carbon nanotube–polypyrrole composite. Thus, this immunosensor has the advantage of electrochemical detection without adding any redox-probe solution (probe-less detection), allowing a point-of-care diagnosis. It was responsive to serum samples of only ZIKV positive patients and non-responsive to negative ZIKV patients, even if the sample was DENV positive, indicating a possible differential diagnosis between them by NS2B. All samples used here were confirmed by CDC protocols, and immunosensor responses were also checked in the supernatant of C6/36 and in Vero cell cultures infected with ZIKV.

scholarly journals Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 302 ◽  
Author(s):  
Anthony C. Ike ◽  
Chisom J. Onu ◽  
Chukwuebuka M. Ononugbo ◽  
Eleazar E. Reward ◽  
Sophia O. Muo
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infections ◽  
Recombinant Dna ◽  
Vaccine Development ◽  
The Body ◽  
Effective Vaccine ◽  
Subunit Vaccines ◽  
Simplex Virus ◽  
Hsv Infections

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

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