Serological Study of Neutralizing Antibodies Against Enterovirus D68 Among Healthy Population in Xiamen, China

Abstract Background: Enterovirus D68 (EV-D68) infections poses a serious public health threat, which caused outbreaks of severe respiratory illness and has been closely associated with "polio-like" central nervous system disease. The patterns of immune responses to EV-D68 have not been fully understood. This study was performed to investigate the level of neutralizing antibody against EV-D68 among the healthy population in Xiamen City.Methods: A total of 515 serum samples from healthy people were selected by stratified random sampling in Xiamen City in 2016, and the titer of neutralizing antibody against EV-D68 was detected by an efficient micro-neutralization assay.Results: The overall seroprevalence of neutralizing antibody against EV-D68 was 81.9%, and the overall geometric mean titers (GMT) was 248.0. The positive rates were 42.2%, 49.3%, 71.9%, 94.2% and 98.5%, respectively, in groups of <1, 1-3, 4-6, 7-19 and 20-39 years old, and were up to 100% in the 40-59 and ≥ 60 age groups. The GMTs in these seven groups were 1:39.8, 1:80.6, 1:133.2, 1:283.7, 1:253.3, 1:308.1 and 1:405.0, respectively. The seroprevalence and GMT of EV-D68 showed an increased trend with age, while gender and geographic area didn’t show significant impact.Conclusions: EV-D68 infection was prevalent in Xiamen City. Children are the high-risk groups for EV-D68-related illnesses, especially those aged ≤ 3 years. It is necessary to establish preventive measures and strengthened the surveillance on EV-D68 to prevent disease outbreaks.

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Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

10.1101/2021.07.16.21260618 ◽

2021 ◽

Author(s):

Yu-An Kung ◽

Chung-Guei Huang ◽

Sheng-Yu Huang ◽

Kuan-Ting Liu ◽

Peng-Nien Huang ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Development ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Diagnostic Techniques ◽

International Standards ◽

World Health ◽

Serum Samples ◽

Antibody Titers ◽

Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

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Prevalence and Persistence of Maternal Dengue Neutralizing Antibodies in Infants From Central and Southern Thailand: A Retrospective Cohort Study

Asia Pacific Journal of Public Health ◽

10.1177/1010539519853396 ◽

2019 ◽

Vol 31 (4) ◽

pp. 288-295 ◽

Cited By ~ 1

Author(s):

Adrienne Guignard ◽

François Haguinet ◽

Stéphanie Wéry ◽

Phirangkul Kerdpanich

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Development ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Maternal Antibodies ◽

Childhood Immunization ◽

Serum Samples ◽

Denv Serotypes ◽

Antibody Titers ◽

Antibody Kinetics

Understanding maternal dengue virus (DENV) neutralizing antibody kinetics in infants remains timely to develop a safe and effective childhood immunization. This retrospective study evaluated the prevalence and persistence of maternal antibody titers against DENV serotypes 1 to 4 in 139 Thai infants at 2, 6, and 7 months of age, using serum samples collected in a vaccination trial ( http://clinicaltrials.gov ; NCT00197275). Neutralizing antibodies against all 4 DENV serotypes were detected in 87.8% and 22.9% of infants at 2 and 7 months, respectively. At 2 months, DENV-4 neutralizing antibody geometric mean titers were notably lower (80) compared with DENV-1 to DENV-3 (277-471). Our results corroborate previous findings that DENV-1 to DENV-4 maternal antibodies persist at 7 months despite titers decrease from 2 months onwards. As persisting maternal antibodies may inhibit immune responses in DENV-vaccinated infants, a comprehensive understanding of DENV antibody kinetics is required in the perspective of vaccine development for infants.

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Persistence of Neutralizing Antibodies to SARS-CoV-2 in First Wave Infected Individuals at Ten Months Post-Infection: The UnIRSA Cohort Study

Viruses ◽

10.3390/v13112270 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2270

Author(s):

Gloria Griffante ◽

Shikha Chandel ◽

Daniela Ferrante ◽

Valeria Caneparo ◽

Daniela Capello ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Development ◽

Natural Infection ◽

Large Fraction ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Northern Italy ◽

Serum Samples ◽

Neutralization Titer ◽

Igg Antibody

Longitudinal mapping of antibody-based SARS-CoV-2 immunity is critical for public health control of the pandemic and vaccine development. We performed a longitudinal analysis of the antibody-based immune response in a cohort of 100 COVID-19 individuals who were infected during the first wave of infection in northern Italy. The SARS-CoV-2 humoral response was tested using the COVID-SeroIndex, Kantaro Quantitative SARS-CoV-2 IgG Antibody RUO Kit (R&D Systems, Bio-Techne, Minneapolis, USA) and pseudotype-based neutralizing antibody assay. Using sequential serum samples collected from 100 COVID-19 recovered individuals from northern Italy—mostly with mild disease—at 2 and 10 months after their first positive PCR test, we show that 93% of them seroconverted at 2 months, with a geometric mean (GeoMean) half-maximal neutralization titer (NT50) of 387.9. Among the 35 unvaccinated subjects retested at 10 months, 7 resulted seronegative, with an 80% drop in seropositivity, while 28 showed decreased anti-receptor binding domain (RBD) and anti-spike (S) IgG titers, with a GeoMean NT50 neutralization titer dropping to 163.5. As an NT50 > 100 is known to confer protection from SARS-CoV-2 re-infection, our data show that the neutralizing activity elicited by the natural infection has lasted for at least 10 months in a large fraction of subjects.

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SARS-CoV-2 antibodies remain detectable 12 months after infection and antibody magnitude is associated with age and COVID-19 severity

10.1101/2021.04.27.21256207 ◽

2021 ◽

Author(s):

Eric D. Laing ◽

Nusrat J. Epsi ◽

Stephanie A. Richard ◽

Emily C. Samuels ◽

Wei Wang ◽

...

Keyword(s):

Symptom Onset ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Serum Samples ◽

Military Hospitals ◽

Igg Binding ◽

One Year

ABSTRACTImportanceThe persistence of SARS-CoV-2 antibodies may be a predictive correlate of protection for both natural infections and vaccinations. Identifying predictors of robust antibody responses is important to evaluate the risk of re-infection / vaccine failure and may be translatable to vaccine effectiveness.ObjectiveTo 1) determine the durability of anti-SARS-CoV-2 IgG and neutralizing antibodies in subjects who experienced mild and moderate to severe COVID-19, and 2) to evaluate the correlation of age and IgG responses to both endemic human seasonal coronaviruses (HCoVs) and SARS-CoV-2 according to infection outcome.DesignLongitudinal serum samples were collected from PCR-confirmed SARS-CoV-2 positive participants (U.S. active duty service members, dependents and military retirees, including a range of ages and demographics) who sought medical treatment at seven U.S. military hospitals from March 2020 to March 2021 and enrolled in a prospective observational cohort study.ResultsWe observed SARS-CoV-2 seropositivity in 100% of inpatients followed for six months (58/58) to one year (8/8), while we observed seroreversion in 5% (9/192) of outpatients six to ten months after symptom onset, and 18% (2/11) of outpatients followed for one year. Both outpatient and inpatient anti-SARS-CoV-2 binding-IgG responses had a half-life (T1/2) of >1000 days post-symptom onset. The magnitude of neutralizing antibodies (geometric mean titer, inpatients: 378 [246-580, 95% CI] versus outpatients: 83 [59-116, 95% CI]) and durability (inpatients: 65 [43-98, 95% CI] versus outpatients: 33 [26-40, 95% CI]) were associated with COVID-19 severity. Older age was a positive correlate with both higher IgG binding and neutralizing antibody levels when controlling for COVID-19 hospitalization status. We found no significant relationships between HCoV antibody responses and COVID-19 clinical outcomes, or the development of SARS-CoV-2 neutralizing antibodies.Conclusions and RelevanceThis study demonstrates that humoral responses to SARS-CoV-2 infection are robust on longer time-scales, including those arising from milder infections.However, the magnitude and durability of the antibody response after natural infection was lower and more variable in younger participants who did not require hospitalization for COVID-19. These findings support vaccination against SARS-CoV-2 in all suitable populations including those individuals that have recovered from natural infection.

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Immunogenicity in sheep of Uruguayan commercial vaccines against bovine alphaherpesvirus 1, 5 and bovine pestiviruses

Ciência Rural ◽

10.1590/0103-8478cr20190465 ◽

2020 ◽

Vol 50 (4) ◽

Author(s):

Ingryd Merchioratto ◽

Alana de Almeida Aurélio ◽

Janice Machado Villela ◽

Nicole Vieira Stone ◽

Isac Junior Roman ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Serological Response ◽

Serum Samples ◽

Post Vaccination ◽

Immunological Responses ◽

Antibody Titers ◽

Low Levels

ABSTRACT: The serological responses induced by four commercial inactivated Uruguayan vaccines against bovine alphaherpesviruses (BoHV)-1 and -5 and bovine pestiviruses (BVDV-1, BVDV-2, and HoBiPeV) were evaluated in sheep. Thirty-seven sheep were immunized twice (day 0 and 25) and their serum samples were tested at different intervals (days 0, 25, 40, 60, and 90) post-vaccination (PV). Among the four vaccines tested, only one (G4) could induce the production of moderate neutralizing antibody titers against BoHV-1 and -5 and BVDV-1 and -2. The G3 vaccine showed a neutralizing serological response against the bovine alphaherpesviruses only. The G1 and G2 vaccines produced extremely low levels of antibodies in a few vaccinated animals only (geometric mean titers (GMT) 2.2). Similar levels of immunological responses were induced by the G4 vaccine against BoHV-1 and -5, and titers of neutralizing antibodies induced in approximately 70% of the animals are known to confer protection (GMT > 8). For bovine pestiviruses, the vaccine stimulated response of G4 against BVDV-2 was higher compared to that against BVDV-1, and extremely low for HoBiPeV. The peak of neutralizing antibodies to BoHV-1 and BVDV-1 was observed on days 40 and 60 PV, respectively. Thereafter, a remarkably decrease in neutralizing antibody response was observed at day 90 PV. These results demonstrated that tested commercial Uruguayan vaccines did not induce a serological response of adequate magnitude and duration. Thus, it is important to periodically review formulations and compositions of commercial vaccines against bovine alphaherpesviruses and pestiviruses.

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First seroepidemiological investigation of human enterovirus 71 in Iran

Iranian Journal of Microbiology ◽

10.18502/ijm.v13i4.6975 ◽

2021 ◽

Author(s):

Mahsa Javadi ◽

Ahmad Nejati ◽

Maryam Yousefi ◽

Mahmood Mahmoodi ◽

Zabihollah Shoja ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neurological Diseases ◽

Age Groups ◽

Enterovirus 71 ◽

Neutralizing Antibody ◽

Human Enterovirus ◽

Healthy Individuals ◽

Serum Samples ◽

Cross Sectional ◽

Human Enterovirus 71

Background and Objectives: Human Enterovirus 71 (EV-A71) is the causative agent for many dermal to neurological diseases especially polio-like paralysis outbreaks around the world. This study, the first of this kind in Iran, aimed to find neu- tralizing antibodies against EV-A71 in serum of healthy individuals in different age groups based on neutralization test (NT). Materials and Methods: In this cross-sectional study, 547 serum samples were collected from healthy individuals who were referring for routine checkup tests (aged from under 6 months to over 31 years old) to Imam-Khomeini Hospital in Tehran during January-December 2015. Serum samples were examined by NT in cell culture to detect neutralizing antibodies against EV-A71. In the next step, some of the positive samples were subjected to complete titration to determine the exact titer of anti-EV-A71 antibodies. Results: Of 547 samples, 310 (56.7%) were positive for EV-A71 neutralizing antibody. The presence of the antibody in- creased with age (p<0.001), and there was a significant statistical relationship between sex and the presence of antibody (p=0.009). Conclusion: Our results demonstrated an apparent but limited circulation of EV-A71 in our society. After the worldwide eradication of poliovirus, EV-A71 which can cause polio-likes syndrome, might be the new challenge for our health care system as regard more in depth research is however needed.

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The prevalence of diphtheria immunity in healthy population in Poland

Epidemiology and Infection ◽

10.1017/s0950268801005295 ◽

2001 ◽

Vol 126 (2) ◽

pp. 225-230 ◽

Cited By ~ 9

Author(s):

J. WALORY ◽

P. GRZESIOWSKI ◽

W. HRYNIEWICZ

Keyword(s):

Geometric Mean ◽

Age Groups ◽

Significant Proportion ◽

Reference Method ◽

Vero Cells ◽

Healthy Population ◽

Serum Samples ◽

Booster Immunization ◽

Age Related ◽

Significant Difference

The degree of seroprotection against diphtheria in Poland was evaluated by determination of IgG antibodies to Corynebacterium diphtheriae toxin (IgG-DTAb). The study population consisted of 4829 healthy subjects aged from 1 day to 85 years from 7 regions of Poland. Serum samples collected between 1996 and 1998 were assayed for IgG-DTAb antibodies using a toxoid enzyme immunoassay. Neutralization of toxin in Vero cells was performed as a reference method with the WHO standard for human diphtheria antitoxin. The study revealed a lack of seroprotection (IgG-DTAb < 0·1 IU/ml) in 23 % of individuals, basic seroprotection (0·1–1·0 IU/ml) in 64 %, and effective seroprotection (> 1·0 IU/ml) in 13 %. The non-protected group consisted of non-vaccinated children below 2 months of age (10 %), individuals between 2 months and 18 years old (20 %) and greater than 19 years old (70 %). Of the adults, 32 % were seronegative, 63 % had basic seroprotection and only 5 % were fully protected; 43 % of adults between 30 and 64 years, who had not been vaccinated at least during the previous 10 years were not protected against diphtheria. The geometric mean titre (GMT) of IgG-DTAb was 0·25 IU/ml in the total population. Age-related GMTs differed significantly from each other and were higher (0·44 IU/ml) in individuals from 2 months to 18 years old, compared with 0·14 IU/ml and 0·17 IU/ml in children under 2 months and adults, respectively. No significant difference was found in the GMTs of men and women in all age groups. We conclude that the currently used vaccination programme in Poland is highly effective and assures protection against diphtheria in the majority of the population in the 10-year period following the last booster. However, a significant proportion of adults between 30 and 64 years lack protection and this indicates a need for booster immunization for this group.

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Effectiveness of the SA 14-14-2 Live-Attenuated Japanese Encephalitis Vaccine in Myanmar

Vaccines ◽

10.3390/vaccines9060568 ◽

2021 ◽

Vol 9 (6) ◽

pp. 568

Author(s):

Mya Myat Ngwe Tun ◽

Aung Kyaw Kyaw ◽

Khine Mya Nwe ◽

Shingo Inoue ◽

Kyaw Zin Thant ◽

...

Keyword(s):

Japanese Encephalitis ◽

Neutralizing Antibodies ◽

Geometric Mean ◽

Vaccination Campaign ◽

Age Groups ◽

Neutralizing Antibody ◽

Blood Collection ◽

Cross Sectional ◽

Single Time ◽

Japanese Encephalitis Vaccine

Myanmar is an endemic country for the Japanese encephalitis virus (JEV), and the SA-14-14-2 live-attenuated JEV vaccine was first introduced as a catch-up vaccination campaign in 2017. To determine the effectiveness of vaccination by means of neutralizing antibody titers against JEV, a cross-sectional descriptive study was conducted among five to 15-year-old monastic school children in Mandalay, Myanmar. A total of 198 students who had received vaccines were recruited, and single-time investigation of anti-JEV IgG and neutralizing antibodies against wild-type JEV were determined using anti-JEV IgG ELISA and plaque reduction neutralization tests (PRNT50). All students 100% (198/198) showed positive results on the anti-JEV IgG ELISA, and 87% (172/198) of the students had neutralizing antibodies against JEV six months after immunization. The geometric mean titers of both IgG antibodies and neutralizing antibodies increased with the participants’ age groups, and statistically significant differences in anti-JEV IgG titers were noted across age groups. In this study, we could not investigate the persistence of neutralizing antibodies as only single-time blood collection was done. This study, which is the first report of JEV vaccination among children in Myanmar, showed similar neutralizing antibody production rates among vaccinated individuals as did studies in other countries.

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

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00588-2 ◽

2021 ◽

Author(s):

Vincent Legros ◽

Solène Denolly ◽

Manon Vogrig ◽

Bertrand Boson ◽

Eglantine Siret ◽

...

Keyword(s):

Intensive Care ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Surface Protein ◽

Humoral Response ◽

Neutralizing Antibody ◽

Rapid Decline ◽

Serum Samples ◽

Immune Correlates ◽

Human Coronaviruses

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

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Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

Clinical and Vaccine Immunology ◽

10.1128/cvi.05065-11 ◽

2011 ◽

Vol 18 (9) ◽

pp. 1406-1409 ◽

Cited By ~ 44

Author(s):

Beatriz Mariana Abramczuk ◽

Taís Nitsch Mazzola ◽

Yara Maria Franco Moreno ◽

Tatiane Queiroz Zorzeto ◽

Wagner Quintilio ◽

...

Keyword(s):

Hepatitis B ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Geometric Mean ◽

Humoral Response ◽

Vaccine Response ◽

Serum Samples ◽

Hiv Exposed ◽

Exposed Uninfected

ABSTRACTLittle is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, ≥1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders (χ2=10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.

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