Regional differences in vaccine uptake and serological responses to vaccine and circulating strains of H1N1 viruses among patients with confirmed influenza

BackgroundSeasonal epidemics of influenza are often characterized through national or international surveillance efforts to determine vaccine efficacy and vaccine strain selection, but they do not provide detailed information about local variations in factors that can influence influenza cases and disease severity.MethodsSurveillance for influenza like illness was performed in Emergency Medicine Departments in Taipei, Taiwan and Baltimore, Maryland during the winter of 2015-16. Detailed demographic and clinical data were obtained. Nasal swabs or washes were collected for influenza virus diagnosis, sequencing and isolation. Serum was collected to determine neutralizing antibody levels.ResultsH1N1 viruses dominated both sites, but more influenza cases occurred in Taipei compared to Baltimore. H1 HA clade diversity was greater in Taipei. Vaccination rates were lower in Taipei than Baltimore, but vaccination was associated with an increase in serum neutralizing antibodies to recent H1N1 strains in Taipei, but not Baltimore. There was a higher level of preexisting immunity to circulating H1N1 strains in Baltimore.ConclusionsRegional differences in preexisting immunity and H1N1 strain circulation may have contributed to the vastly different 2015-16 influenza seasons in Taipei and Baltimore and suggest immune responses to vaccination can be affected by the degree of preexisting immunity in the population.

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Duration of immunity against COVID-19 after vaccination in Indian subcontinent

10.21203/rs.3.rs-1260289/v1 ◽

2022 ◽

Author(s):

Apoorva Munigela ◽

Sasikala M ◽

Gujjarlapudi Deepika ◽

Anand V Kulkarni ◽

Krishna Vemula ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Booster Dose ◽

Indian Subcontinent ◽

Neutralizing Antibody ◽

Health Concern ◽

Mortality Data ◽

Optimal Timing ◽

Cross Sectional ◽

Mortality And Morbidity ◽

Antibody Levels

Abstract Coronavirus disease (COVID-19) continues to be a major health concern leading to substantial mortality and morbidity across the world. Vaccination is effective in reducing the severity and associated mortality. Data pertaining to the duration of immunity, antibody waning and the optimal timing of booster dose administration is limited. In this cross-sectional study, we assessed the antibody levels in healthcare workers who were fully vaccinated after obtaining Institutional ethics committee approval and informed consent. Whole blood was collected and enumeration of S1/S2 neutralizing antibody levels was carried out using LIAISON SARS-COV-2 S1/S2 IgG assay. A total of 1636 individuals who were vaccinated with Covaxin or Covishield were included. Of these, 52% were males with a median age of 29 years. Diabetes and Hypertension was noted in 2.32% (38/1636) and 2.87% (47/1636) of the individuals. Spike neutralizing antibodies were below the detectable range (<15 AU/ml) in 6.0% (98/1636) of the individuals. Decline in neutralizing antibody was seen in 30% of the individuals above 40 years of age with comorbidities (diabetes and hypertension) after 6 months. These individuals may be prioritized for a booster dose at 6 months.

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Clinical utility of Corona Virus Disease-19 serum IgG, IgM, and neutralizing antibodies and inflammatory markers

10.1101/2021.01.19.21249604 ◽

2021 ◽

Author(s):

Ernst J. Schaefer ◽

Florence Comite ◽

Latha Dulipsingh ◽

Maxine Lang ◽

Jessica Jimison ◽

...

Keyword(s):

Inflammatory Markers ◽

Neutralizing Antibodies ◽

Clinical Utility ◽

Virus Disease ◽

Neutralizing Antibody ◽

Case Finding ◽

Immunoglobulin M ◽

Serum Igg ◽

Older Subjects ◽

Antibody Levels

AbstractMost deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed age effects and clinical utility of serum SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies and serum inflammatory markers. Serum IgG, IgM, and neutralizing antibody levels were measured using chemiluminescence assays from Diazyme (Poway, CA), while serum interleukin-6 (IL-6), C reactive protein (CRP), and ferritin were measured with immunoassays obtained from Roche (Indianapolis, IN). In 79,005 subjects, IgG and IgM levels were positive (≥1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively. In antibody positive subjects, median IgG levels were 3.93 AU/mL if <45 years of age, 10.18 AU/mL if 45-64 years of age, and 10.85 AU/mL if ≥65 years of age (p<0.0001). In SARS-CoV-2 RNA positive cases, family members and exposed subjects (n=1,111), antibody testing was found to be valuable for case finding, and persistent IgM levels were associated with chronic symptoms. In non-hospitalized and hospitalized subjects assessed for SARS-CoV-2 RNA (n=278), median IgG levels in AU/mL were 0.05 in negative subjects (n=100), 14.83 in positive outpatients (n=129), and 30.61 in positive hospitalized patients (n=49, p<0.0001). Neutralizing antibody levels correlated significantly with IgG (r=0.875; p<0.0001). Two or more of the criteria of IL-6 ≥10 pg/mL, CRP ≥10 mg/L, and/or IgM >1.0 AU/mL occurred in 97.7% of inpatients versus 1.8% of outpatients (>50-fold relative risk, C statistic 0.986, p<0.0001). Our data indicate that: 1) IgG levels are significantly higher in positive older subjects, possibly to compensate for decreased cellular immunity with aging; 2) IgG levels are important for case finding in family clusters; 3) IgG levels are significantly correlated with neutralizing antibody levels; 4) persistently elevated IgM levels are associated with chronic disease; and 5) markedly elevated IL-6, hs-CRP, and/or positive IgM accurately identify SARS-CoV-2 RNA positive subjects requiring hospitalization.

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Neutralizing Antibody Responses in COVID-19 Convalescent Sera

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa673 ◽

2020 ◽

Vol 223 (1) ◽

pp. 47-55 ◽

Cited By ~ 1

Author(s):

William T Lee ◽

Roxanne C Girardin ◽

Alan P Dupuis ◽

Karen E Kulas ◽

Anne F Payne ◽

...

Keyword(s):

Neutralizing Antibodies ◽

High Titer ◽

Experimental Treatment ◽

Neutralizing Antibody ◽

Maximal Activity ◽

The United States ◽

Enzyme Linked Immunosorbent Assay ◽

United States Food ◽

Antibody Titers ◽

Antibody Levels

Abstract Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.

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Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

10.21203/rs.3.rs-916427/v1 ◽

2021 ◽

Author(s):

Annika Fendler ◽

Lewis Au ◽

Scott Shepherd ◽

Fiona Byrne ◽

Maddalena Cerrone ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Cellular Responses ◽

Patients With Cancer ◽

Cell Immunity ◽

Clinical Annotation ◽

Antibody Titers ◽

Antibody Levels ◽

Immune Profiling ◽

Reactive Antibody

Abstract Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer.

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Vaccine-Associated Disease Enhancement (VADE): Considerations in Postvaccination COVID-19

Case Reports in Medicine ◽

10.1155/2021/9673453 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Rahajeng N. Tunjungputri ◽

Erpryta Nurdia Tetrasiwi ◽

Merlinda Veronica ◽

Jacub Pandelaki ◽

Fera Ibrahim ◽

...

Keyword(s):

Decision Making ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Vaccine Uptake ◽

The Public ◽

True Incidence ◽

Mass Immunization ◽

History Of ◽

New Phase

Introduction. The COVID-19 pandemic has entered a new phase with the roll-out of several vaccines worldwide at an accelerated phase. The occurrence of a more severe presentation of COVID-19 after vaccination may affect policymakers’ decision-making and vaccine uptake by the public. Vaccine-associated disease enhancement (VADE) is the modified presentation of infections in individuals after having received a prior vaccination. Currently, little is known about the potential of vaccine-associated disease enhancement (VADE) following COVID-19 immunization. Case Illustration. We herewith report two patients admitted with confirmed COVID-19 pneumonia with a history of CoronaVac vaccination. The first patient with a relatively milder course of the disease had received two doses of CoronaVac, whereas the second patient with a more progressive course of the disease received only one dose before developing symptoms and being admitted to the hospital. Our observations suggest that vaccination could act in boosting the inflammatory process and reveal the previously asymptomatic COVID-19 illness. Theoretically, vaccines could induce VADE, where only suboptimal, nonprotective titers of neutralizing antibodies were produced or proinflammatory T-helper type 2 response was induced. Secondly, enhanced respiratory disease (ERD) could manifest, where pulmonary symptoms are more severe due to peribronchial monocytic and eosinophilic infiltration. Understanding VADE is important for the decision-making by the public, clinicians, and policymakers and is warranted for successful vaccination uptake. Conclusion. We report two cases of patients developing COVID-19 shortly after CoronaVac vaccination in which VADE is likely. We recommend that current vaccination strategies consider the measurement of neutralizing antibody titer as a guide in ensuring the safest strategy for mass immunization. Studies are needed to investigate the true incidence of VADE on vaccinated individuals as well as on how to differentiate between VADE and severe manifestations of COVID-19 that are unrelated to vaccination.

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SARS-CoV-2 Neutralizing Antibody Levels Post COVID-19 Vaccination Based on ELISA Method—A Small Real-World Sample Exploration

Vaccines ◽

10.3390/vaccines9101139 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1139

Author(s):

Xiaoguang Li ◽

Chao Liang ◽

Xiumei Xiao

Keyword(s):

Neutralizing Antibodies ◽

Detection Rate ◽

Neutralizing Antibody ◽

Population Characteristics ◽

Detection Rates ◽

Positive Detection Rate ◽

Significant Difference ◽

Positive Rate ◽

Antibody Levels

This study investigated the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies following inoculation with the coronavirus disease (COVID-19) vaccine. From June to July 2021, 127 participants who had completed COVID-19 vaccination (inactivated SARS-CoV-2 vaccine, 64; CoronaVac, 61; CanSino, 2) were recruited and tested using SARS-CoV-2 neutralizing antibody kits. The positive detection rate (inhibition of neutralizing antibodies ≥ 30%) was calculated and stratified according to population characteristics and inoculation time. The positive rate of neutralizing antibody was 47.22% (17/36) in men and 53.85% (49/91) in women, and 54.55% (24/44) in BMI ≥ 24 and 50.60% (42/83) in BMI < 24. Age was stratified as 20–29, 30–39, 40–49, and ≥50; positive detection rates of SARS-CoV-2 neutralizing antibodies were observed in 60.00% (24/40), 50.00% (21/42), 48.39% (15/31), and 42.86% (6/14), respectively, but with no significant difference (x2 = 1.724, p = 0.632). Among 127 vaccinated participants, 66 (51.97%) were positive. The positive detection rate was 63.93% (39/61) with CoronaVac and 42.19% (27/64) with the inactivated SARS-CoV-2 vaccine (significance x2 = 5.927, p = 0.015). Multivariate analysis revealed a significant difference in vaccination times, with average vaccination weeks in the positive and negative groups of 11.57 ± 6.48 and 17.87 ± 9.17, respectively (t= −4.501, p < 0.001). The positive neutralizing antibody rate was 100.00%, 60.00%, 58.33%, 55.56%, 43.14%, 28.57%, and 0.00% at 2–4, 5–8, 9–12, 13–16,17–20, 21–24, and >24 weeks, respectively (x2 = 18.030, p = 0.006). Neutralizing antibodies were detected after COVID-19 inoculation, with differences relating to inoculation timing. This study provides a reference for vaccine evaluation and follow-up immunization strengthening.

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Expansion of SARS-CoV-2-specific Antibody-secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients

10.1101/2020.05.28.118729 ◽

2020 ◽

Cited By ~ 1

Author(s):

Renata Varnaitė ◽

Marina García ◽

Hedvig Glans ◽

Kimia T. Maleki ◽

John Tyler Sandberg ◽

...

Keyword(s):

B Cell ◽

Specific Antibody ◽

Neutralizing Antibodies ◽

Cell Activation ◽

Neutralizing Antibody ◽

Antibody Responses ◽

B Cell Activation ◽

Immunological Parameters ◽

Antibody Secreting Cell ◽

Antibody Levels

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global pandemic. Pathogen-specific antibodies are typically a major predictor of protective immunity, yet B cell and antibody responses during COVID-19 are not fully understood. Here, we analyzed antibody-secreting cell (ASC) and antibody responses in twenty hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19, and presented with reduced lymphocyte numbers and increased T cell and B cell activation. Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific ASCs in all twenty COVID-19 patients using a multicolor FluoroSpot assay. Out of the 20 patients, 16 had developed SARS-CoV-2-neutralizing antibodies by the time of inclusion in the study. SARS-CoV-2-specific IgA, IgG and IgM antibody levels positively correlated with SARS-CoV-2-neutralizing antibody titers, suggesting that SARS-CoV-2-specific antibody levels may reflect the titers of neutralizing antibodies in COVID-19 patients during the acute phase of infection. Lastly, we showed that interleukin 6 (IL-6) and C-reactive protein (CRP) concentrations were higher in serum of patients who were hospitalized for longer, supporting the recent observations that IL-6 and CRP could be used to predict COVID-19 severity. Altogether, this study constitutes a detailed description of clinical and immunological parameters in twenty COVID-19 patients, with a focus on B cell and antibody responses, and provides tools to study immune responses to SARS-CoV-2 infection and vaccination.

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Clinical utility of Elecsys Anti-SARS-CoV-2 S assay in COVID-19 vaccination: An exploratory analysis of the mRNA-1273 phase 1 trial

10.1101/2021.10.04.21264521 ◽

2021 ◽

Author(s):

Simon Jochum ◽

Imke Kirste ◽

Sayuri Hortsch ◽

Veit Peter Grunert ◽

Holly Legault ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Clinical Utility ◽

Dose Group ◽

Phase 1 ◽

Geometric Mean ◽

Neutralizing Antibody ◽

High Specificity ◽

Live Virus ◽

Phase 1 Trial ◽

Antibody Levels

Background The ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461). Methods Samples from 30 healthy participants, aged 18-55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL - equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50). Results RBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but 2 participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels were 3.27-7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson's r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate-strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p≤0.0001). Conclusion The Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination, and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response.

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SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

10.1101/2021.01.30.428921 ◽

2021 ◽

Author(s):

Ramon Roozendaal ◽

Laura Solforosi ◽

Daniel Stieh ◽

Jan Serroyen ◽

Roel Straetemans ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Protective Efficacy ◽

Rhesus Macaques ◽

Natural Infection ◽

Neutralizing Antibody ◽

Preliminary Evidence ◽

Correlates Of Protection ◽

Antibody Titers ◽

Antibody Levels ◽

The Relationship

The first COVID-19 vaccines have recently gained authorization for emergency use.1,2 At this moment, limited knowledge on duration of immunity and efficacy of these vaccines is available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short lived,3,4 and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection.5 Here we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike (S) protein in rhesus macaques6,7,8 and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We find that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of S-binding and neutralizing antibodies. These results suggest that Ad26.COV2.S could confer durable protection in humans and that immunological correlates of protection may enable the prediction of durability of protection.

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Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals

10.1101/2021.02.01.21250493 ◽

2021 ◽

Author(s):

Alena J. Markmann ◽

Natasa Giallourou ◽

D. Ryan Bhowmik ◽

Yixuan J. Hou ◽

Aaron Lerner ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Human Antibody ◽

Antibody Titers ◽

Sex Disparities ◽

Binding Antibody ◽

Male Sex ◽

Antibody Levels ◽

First Time

AbstractThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.SignificanceIn this study we found that neutralizing antibody responses in COVID-19 convalescent individuals vary in magnitude but are durable and correlate well with RBD Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time, that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardio-metabolic co-morbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2.

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