2805. Kinetics of Anti-Zika Virus (ZIKV) Antibodies after Acute Infection in Pregnant Women

Abstract Background The kinetics and specificity of anti-ZIKV antibodies after acute ZIKV infection is not well known, especially in areas where different flaviviruses circulate. The objective of this study was to describe the kinetics of anti-ZIKV antibodies in pregnant women in whom an acute ZIKV infection was identified during pregnancy. Methods Within a cohort of pregnant women living in Guadeloupe and exposed to ZIKV during the 2016 zika outbreak, we identified 65 women who presented with an acute, symptomatic PCR-confirmed ZIKV infection at various times of their pregnancy, with a known date of first Zika symptom. Anti-ZIKV neutralizing antibodies (using a Virus Neutralisation Test (VNT)) and anti-ZIKV NS1 antibodies (using IgM and IgG ELISA Euroimmun® kits) were searched for on frozen serum samples obtained from blood drawn at the time of delivery in all women and at various times between acute infection and delivery in 23 women. Results Patients’ mean age was 30 years and ZIKV infection had occurred during the first, second, and third trimester of pregnancy in 14 (21%), 35 (54%), and 16 (25%) women, respectively. ZIKV serology on delivery samples was positive in 65/65 (100%; one-sided 97.5% CI: 94.4%–100%) women by both VNT and IgG ELISA assays and in 5/65 (8%) women by IgM ELISA assay. In these 5 cases, median time between first symptom and sampling date was 36 days. Results of ELISA assays on the intermediate samples were as follows: IgG antibodies were negative in all 5 samples that had been drawn within 7 days of first symptom and positive in the 18 samples that had been drawn afterwards; IgM antibodies were positive in 10 of the 19 samples that had been drawn within 3 months of first symptom and negative in 2 of the 4 samples that had been drawn afterwards. Conclusion After acute ZIKV infection, IgG antibodies developed and remained detectable until delivery by a commercially available ELISA assay in all women tested. These antibodies were specific of ZIKV, with concomitantly positive VNT results. From these findings, the absence of ZIKV antibodies at delivery would strongly indicate the absence of infection during pregnancy. Disclosures All authors: No reported disclosures.

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Examination of convalescents after West Nile fever for the specific IgM, IgG and neutralizing antibodies

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40890 ◽

2016 ◽

Vol 21 (2) ◽

pp. 82-86

Author(s):

Alla R. Azaryan ◽

A. A Kozlova ◽

A. P Grishanova ◽

E. I Ivashchenko ◽

G. L Shendo ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Igg Antibodies ◽

West Nile Fever ◽

Serum Samples ◽

West Nile ◽

Negative Results ◽

Igm Elisa ◽

Control Research ◽

Specific Igg ◽

Specific Igg Antibodies

The examination was executed in the Astrakhan region over 2013-2014 with participation of three laboratories. In 26 convalescents after West Nile Fever (WNF) with the serological confirmed diagnosis of WNF blood sera were examined. Neurological form of WNF was observed in 8 cases, and febrile form - in 8 convalescents. Sera have been collected in 243-358 days, on average, in 308 days after the beginning of a disease. For their examination there were used IFA-IgM ELISA (MAC-ELISA), IgG ELISA methods as well as neutralization test in Vero E6 cell culture. The results of the examination in 24 of 26 patients (92, 3%) for IgM antibodies to the virus WNF were negative. In two convalescents according to the laboratories in Astrakhan and Moscow in sera there were observed low titers of IgM (1:400) with minor indices of sera optical density (0.3 to 0.4) and negative results in the Volgograd Plague Control Research Institute. Serum samples of other two convalescents were weakly positive or questionable in testing in Volgograd, but were negative when examined in the Institute of Virology. Specific IgG antibodies were detected in 23 of 26 convalescents (88.5%), neutralizing in 22 of 24 (91.7 %). These data confirm the adequacy of the criteria and tactics for WNF serodiagnosis adopted in Russia based on the application of the MAC -ELISA (IFA - IgM).

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Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G, B.1.1.7 and B 1.351 Isolates in Microneutralization Assays

Viruses ◽

10.3390/v13060996 ◽

2021 ◽

Vol 13 (6) ◽

pp. 996

Author(s):

Jenni Virtanen ◽

Ruut Uusitalo ◽

Essi M. Korhonen ◽

Kirsi Aaltonen ◽

Teemu Smura ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Acute Infection ◽

Clinical Isolates ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Kinetics Of

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.

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Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

Frontiers in Immunology ◽

10.3389/fimmu.2021.708523 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tiandan Xiang ◽

Boyun Liang ◽

Yaohui Fang ◽

Sihong Lu ◽

Sumeng Li ◽

...

Keyword(s):

Symptom Onset ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Protein S ◽

Igg Antibodies ◽

Neutralizing Activity ◽

Specific Igg ◽

One Year ◽

Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

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Evaluation of a Genus Specific rGroEL 1-524 IgM-ELISA and Commercially ELISA Kits During Course of Leptospirosis in Thailand

10.21203/rs.3.rs-352195/v1 ◽

2021 ◽

Author(s):

Santi Maneewatchararangsri ◽

Galayanee Doungchawee ◽

Thareerat Kalambaheti ◽

Viravarn Luvira ◽

Ngamphol Soonthornworasiri ◽

...

Keyword(s):

Early Detection ◽

Early Diagnosis ◽

Screening Test ◽

Scrub Typhus ◽

Acute Infection ◽

Febrile Illness ◽

High Sensitivity ◽

Elisa Assay ◽

Igm Elisa ◽

Post Onset

Abstract This work, we developed a genus-specific rGroEL1-524 IgM-ELISA assay for using as screening diagnosis of suspected leptospirosis among acute undifferentiated febrile illness patients during acute fever. Ddiagnostic accuracies of rGroEL1–524 IgM-ELISA, and commercial Panbio IgM-ELISA, and Virion-Serion Classic IgG-ELISA were evaluated with Thai 107 leptospirosis sera, and 189 controls, compared to reference culture and/or MAT methods. Sensitivities were 91.7%, 59.6%, and 17.7% for acute- infection, and were 97.1%, 54.8%, and 9.7% for early detection at 1-3 days post-onset of symptoms (DPO1-3), and the specificities were 87.5%, 86.6%, and 74.8% among controls, respectively. The rGroEL1-524 IgM-ELISA had high sensitivity, at 95.9% and 91.2% among culture and MAT negative cases. Impaired specificity on scrub typhus, possibly from antibody-cross reaction to ortholog GroEL. Commercial Panbio IgM-ELISA had sensitivities of 50%, 63.2%, and 89.9% compared with culture, MAT-negative and single MAT-positive cases whereas Virion-Serion IgG-ELISA provided sensitivities of 13.3%, 10.5% and 71.4%, respectively. A rGroEL1-524 IgM-ELISA could be useful as a screening test for early diagnosis. The performance of the commercial ELISA suggests the applicability of IgM-ELISA for diagnosis, while IgG-ELISA is useful for seroprevalence surveys. However, confirmation by reference tests is recommended.

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Distinct cellular immune signatures in acute Zika virus infection are associated with high or low persisting neutralizing antibody titers

10.1101/2021.05.27.446054 ◽

2021 ◽

Author(s):

Elizabeth E. McCarthy ◽

Pamela M. Odorizzi ◽

Emma Lutz ◽

Carolyn P. Smullin ◽

Iliana Tenvooren ◽

...

Keyword(s):

Zika Virus ◽

Neutralizing Antibodies ◽

Viral Infections ◽

Immune Cell ◽

Acute Infection ◽

Neutralizing Antibody ◽

Natural Immunity ◽

Zikv Infection ◽

Antibody Titers ◽

Cellular Immune

Although the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD- B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune "set-point." Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies.

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Zika Virus Serologic Diagnosis by NS1 ELISA in Curacao

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.698 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S302-S303 ◽

Cited By ~ 1

Author(s):

Samantha Manuel ◽

Liane Virginia-Cova ◽

Loubiela Joseph ◽

Chris Roggeveen ◽

Radjin Steingrover

Keyword(s):

Zika Virus ◽

Cross Reactivity ◽

Pregnant Female ◽

Serum Samples ◽

Zikv Infection ◽

Igm Elisa ◽

Pcr Diagnosis ◽

Two Samples ◽

Negative Controls

Abstract Background Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV. Methods ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity. Results Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay. Conclusion In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern. Disclosures All authors: No reported disclosures.

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Development of an E2 ELISA Methodology to Assess Chikungunya Seroprevalence in Patients from an Endemic Region of Mexico

Viruses ◽

10.3390/v11050407 ◽

2019 ◽

Vol 11 (5) ◽

pp. 407 ◽

Cited By ~ 3

Author(s):

Young Chan Kim ◽

César López-Camacho ◽

Nallely Garcia-Larragoiti ◽

Alan Cano-Mendez ◽

Karina Guadalupe Hernandez-Flores ◽

...

Keyword(s):

Acute Infection ◽

Febrile Illness ◽

Population Based ◽

Cross Sectional Study ◽

Elisa Assay ◽

Serum Samples ◽

Endemic Region ◽

Cross Sectional ◽

Healthy Donors ◽

Epidemiological Information

Chikungunya fever is a debilitating disease caused by Chikungunya virus (CHIKV) that can result in long-lasting arthralgias. The early diagnosis of CHIKV relies on PCR during the acute infection phase to allow differential diagnosis with other co-circulating arboviruses such as dengue and Zika. Alternatively, serology can support diagnosis and provide epidemiological information on current and past outbreaks. Many commercial serological ELISA assays are based on the inactivated whole CHIKV, but their sensitivity and specificity show great variability. We produced recombinant CHIKV E2 that is suitable for ELISA assays, which was used for the serodiagnosis of CHIKV infections occurring in an arbovirus endemic Mexican region within Michoacán state. A cross-sectional study was conducted in 2016–2017; sera was obtained from 15 healthy donors and 68 patients presenting undifferentiated febrile illness. Serum samples were screened by RT-PCR and by our in-house ELISA assay. Our results indicate that IgM and IgG anti-CHIKV E2 antibodies were detected with our ELISA assay with higher sensitivity than a commercially available CHIKV ELISA kit. Our simple and sensitive ELISA assay for the serodiagnosis of CHIKV infections can be applied to population-based seroprevalence surveys and has potential for monitoring vaccine immunogenicity in CHIKV vaccine clinical trials.

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Serologic Testing for Zika Virus: Comparison of Three Zika Virus IgM-Screening Enzyme-Linked Immunosorbent Assays and Initial Laboratory Experiences

Journal of Clinical Microbiology ◽

10.1128/jcm.00580-17 ◽

2017 ◽

Vol 55 (7) ◽

pp. 2127-2136 ◽

Cited By ~ 58

Author(s):

Dane Granger ◽

Heather Hilgart ◽

Lori Misner ◽

Jaime Christensen ◽

Sarah Bistodeau ◽

...

Keyword(s):

Zika Virus ◽

Neutralizing Antibodies ◽

Enzyme Linked Immunosorbent Assay ◽

Reference Laboratory ◽

Zikv Infection ◽

Serologic Testing ◽

Igm Elisa ◽

Control And Prevention ◽

Laboratory Experiences ◽

Positive Agreement

ABSTRACT Serologic evaluation for Zika virus (ZIKV) infection currently includes an initial screen using an anti-ZIKV IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) followed by supplemental testing of specimens with nonnegative results by a plaque reduction neutralization test (PRNT). We compared the performance characteristics of three ELISAs for the detection of IgM class antibodies to ZIKV, including the Centers for Disease Control and Prevention (CDC) Zika MAC-ELISA, the InBios ZIKV Detect MAC-ELISA, and the Euroimmun anti-Zika Virus IgM ELISA. Additionally, we present our initial experiences with ZIKV serologic testing from a national reference laboratory perspective. Using both retrospectively and prospectively collected specimens from patients with possible ZIKV infection, we show that the CDC and InBios MAC-ELISAs perform comparably to each other, with positive agreement, negative agreement, and interrater kappa values ranging from 87.5% to 93.1%, 95.7% to 98.5%, and 0.52 to 0.83, respectively. In contrast, comparison of the Euroimmun ZIKV ELISA to either the CDC or InBios MAC-ELISAs resulted in positive agreement, negative agreement, and interrater kappa values ranging from 17.9% to 42.9%, 91.7% to 98.6%, and 0.10 to 0.39, respectively. Among the 19 prospective samples submitted for PRNT, nine were negative, eight specimens had neutralizing antibodies to a flavivirus (unable to be identified), and one sample each was confirmed for ZIKV or dengue virus infection. This study highlights the ongoing challenges associated with serologic diagnosis of ZIKV infection. Although the availability of a commercial serologic test for ZIKV has greatly expanded the national capacity for such testing, the need to further characterize and improve these assays, particularly with regard to specificity, remains.

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Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities

10.21203/rs.3.rs-34709/v4 ◽

2020 ◽

Author(s):

Theerut Densathaporn ◽

Rassamee Sangthong ◽

Monvaris Sakolnapa ◽

Smonrapat Surasombatpattana ◽

Marisa Kemapunmanus ◽

...

Keyword(s):

General Population ◽

Pregnant Women ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Zikv Infection ◽

Factors Associated ◽

Neutralizing Capacity ◽

Southern Thailand ◽

Outbreak Areas ◽

Index Cases

Abstract Background: In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies.Methods: The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity.Results: Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9-51.6%) and 29.7% (23.3-36.0%) in general population, and 24.3% (20.1-28.8%) and 12.8% (9.7-16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples.Conclusion: Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.

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Studies on the level of neutralizing antibodies produced by inactivated COVID-19 vaccines in the real world

10.1101/2021.08.18.21262214 ◽

2021 ◽

Author(s):

Haiying Zhang ◽

Yuyuan Jia ◽

Ying Ji ◽

Xu Cong ◽

Yan Liu ◽

...

Keyword(s):

Real World ◽

Linear Correlation ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Igg Antibodies ◽

Serum Samples ◽

The Real ◽

Significant Difference ◽

Positive Rate ◽

High Linear Correlation

Background Although effective vaccines have been developed against COVID-19, the level of neutralizing antibodies (Nabs) induced after vaccination in the real world is still unknown. To evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China. Methods and findings Serum samples were collected from 1,335 people aged 18 and over who were vaccinated with COVID-19 inactivated vaccine in Peking University People's Hospital from January 19 to June 23, 2021, for detection of COVID-19 antibodies. The WHO standard of SARS-CoV-2 NAbs was detected. The coefficients of variation between the detection results and the true values of the NAbs detected by the WHO standard were all lower than the WHO international standard 3% after the dilution of the original and the dilution of the theoretical concentrations of 500 IU/mL, 250 IU/mL, 125 IU/mL, 72.5 IU/mL, 36.25 IU/mL and 18.125 IU/mL. On day 11-70, the positive rate of NAbs against COVID-19 was 82% to 100%; From day 71 to 332, the positive rate of NAbs decreased to 27%. The level of NAbs was significantly higher at 3-8 Weeks than at 0-3 Weeks. There was a high linear correlation between NAbs and IgG antibodies in 1335 vaccinated patients. NAbs levels were decreased in 31 of 38 people (81.6%) at two time points after the second dose of vaccine. There was no significant difference in age between the group with increased and decreased neutralizing antibody levels (x2 =-0.034, P>0.05). The positive rate of NAbs in the two-dose vaccine group (77.3%) was significantly higher than that in the one-dose group (18.1%), with statistical difference (x2=312.590, P<0.001). A total of 206 people who were 11-70 days after receiving the second dose were tested and divided into three groups: 18-40 years old, 41-60 years old and >60 years old. The positive rates of NAbs in three groups (18-40 years old, 41-60 years old and >60 years old) were 95.14%, 78.43% and 81.8%, respectively. The positive rate of NAbs was significantly higher in 18-40 years old than in 41-60 years old (x2=12.547, P <0.01). The titer of NAbs in 18-40 years old group was significantly higher than that in 41-60 years old group (t=-0.222, P <0.01). The positive rate of NAbs in male group (89.32%) was lower than in female (91.26%), but there was no significant difference (x2=0.222, P >0.05). Conclusions The positive rate of NAbs was the highest from 10 to 70 days after the second dose of vaccine, and the positive rate gradually decreased as time went by. There was a high linear correlation between COVID-19 NAbs and IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age, but not by gender. The highest levels of NAbs were produced between shots 21 to 56 days apart, suggesting that 21 to 56 days between shots is suitable for vaccination.

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