Zika Virus IgM Detection and Neutralizing Antibody Profiles 12-19 Months after Illness Onset.
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SUBMITTER: Griffin I
PROVIDER: S-EPMC6346474 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundFew robust longitudinal data on long-term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset.MethodsThe RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged ≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models.ResultsBetween 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI} = 76.5-92.7%]) compared to those with mild or moderate disease (30.7% [95% CI = 21.1-40.9%] and 63.8% [95% CI = 54.8-71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI = 34.2-7.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI = .47-.92]) and those with a body mass index [BMI] ≥30kg/m2 compared to BMI <25kg/m2 (hazard ratio [HR] 0.62 [95% CI = .39-.97]).ConclusionsCOVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms.
| S-EPMC8522402 | biostudies-literature
Project description:This study aimed to elucidate the 12-month durability of neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients infected during the 2020 workplace outbreaks of coronavirus disease 2019 (COVID-19) in Japan. We followed 33 Japanese patients infected with SARS-CoV-2 in April 2020 for 12 months (12M). Patients were tested for NAbs and for antibodies against the SARS-CoV-2 nucleocapsid (anti-NC-Ab) and antibodies against the spike receptor-binding domain (anti-RBD-Ab). Tests were performed at 2M, 6M, and 12M after the primary infection (api) with commercially available test kits. In 90.9% (30/33) of patients, NAbs persisted for 12M api, though the median titers significantly declined from 78.7% (interquartile range [IQR]: 73.0-85.0%) at 2M, to 59.8% (IQR: 51.2-77.9) at 6M (P = 0.008), and to 56.2% (IQR: 39.6-74.4) at 12M (P<0.001). An exponential decay model showed that the NAb level reached undetectable concentrations at 35.5 months api (95% confidence interval: 26.5-48.0 months). Additionally, NAb titers were significantly related to anti-RBD-Ab titers (rho = 0.736, P<0.001), but not to anti-NC-Ab titers. In most patients convalescing from COVID-19, NAbs persisted for 12M api. This result suggested that patients need a booster vaccination within one year api, even though NAbs could be detected for over two years api. Anti-RBD-Ab titers could be used as a surrogate marker for predicting residual NAb levels.
| S-EPMC9426944 | biostudies-literature
Project description:BackgroundWe studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.MethodsSera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively.ResultsAfter completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19 + individuals (132-fold increase). Age >65 years (β=-0.94, p = 0.001) and malignancy (β=-0.88, p = 0.002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1.10, p = 0.004); (β=-0.66, p = 0.014)], diabetes mellitus [(β=-0.57, p = 0.032); (β=-0.44, p = 0.028)], and systemic steroid use [(β=-0.066, p = 0.032); (β=-0.55, p = 0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2. Post-booster neutralization increased with prior COVID-19 (β = 2.9, p-value < 0.0001), and malignancy reduced neutralization response (β=-0.68, p = 0.03), regardless of infection status.ConclusionMultiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.
| S-EPMC9278145 | biostudies-literature
Project description:Porcine epidemic diarrhea virus (PEDV) causes devastating enteric disease that inflicts huge economic damage on the swine industry worldwide. A safe and highly effective PEDV vaccine that contains only the virus-neutralizing epitopes (not enhancing epitope), as well as a ready-to-use PEDV neutralizing antibody for the passive immunization of PEDV vulnerable piglets (during the first week of life) are needed, particularly for PEDV-endemic farms. In this study, we generated monoclonal antibodies (mAbs) to the recombinant S1 domain of PEDV spike (S) protein and tested their PEDV neutralizing activity by CPE-reduction assay. The mAb secreted by one hybrodoma clone (A3), that also bound to the native S1 counterpart from PEDV-infected cells (tested by combined co-immunoprecipitation and Western blotting), neutralized PEDV infectivity. Epitope of the neutralizing mAb (mAbA3) locates in the S1A subdomain of the spike protein, as identified by phage mimotope search and multiple sequence alignment, and peptide binding-ELISA. The newly identified epitope is shared by PEDV G1 and G2 strains and other alphacoronaviruses. In summary, mAbA3 may be useful as a ready-to-use antibody for passive immunization of PEDV-susceptible piglets, while the novel neutralizing epitope, together with other, previously known protective epitopes, have potential as an immunogenic cocktail for a safe, next-generation PEDV vaccine.
| S-EPMC8778753 | biostudies-literature
Project description:BACKGROUND:The emergence of Zika virus (ZV) in tropical and subtropical areas of the world has created an urgent need for vaccines against ZV. However, approved vaccines that prevent ZV infection are not available. To develop an effective vaccine against ZV infection, a lipidated form of ZV envelope protein domain III that possesses an intrinsic adjuvant property was rationally designed. Our goal was to examine the immunogenicity of recombinant lipidated ZV envelope protein domain III (rLZE3) and evaluate its potential as a vaccine candidate against ZV. METHODS:Recombinant ZV envelope protein domain III (rZE3) and rLZE3 were prepared with an Escherichia coli-based system. Dendritic cell surface marker expression and cytokine production upon stimulation were analyzed to evaluate the function of rLZE3. Neutralizing antibody capacities were evaluated using focus reduction neutralization tests after immunization. To investigate the protective immunity in immunized mice, serum samples collected from immunized mice were adoptively transferred into AG129 mice, and then viremia levels and survival times were examined after ZV challenge. RESULTS:rLZE3 alone but not rZE3 alone efficiently activated dendritic cells in vitro and was taken up by dendritic cells in vivo. Immunization of C57BL/6 mice with rLZE3 alone (without exogenous adjuvant) could induce ZV-specific neutralizing antibody responses. Furthermore, serum samples obtained from rLZE3-immunized mice provided protection as indicated by a reduction in viremia levels and prolongation of survival times after ZV challenge. CONCLUSION:These results indicate that rLZE3 is an excellent vaccine candidate and has great potential that should be evaluated in further preclinical studies.
| S-EPMC7158147 | biostudies-literature
Project description:BackgroundIn 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.MethodsThe 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.ResultsOut 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.ConclusionProtective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.
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Project description:BackgroundUnderstanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, losing sight of the temporal pattern of these changes.MethodsWe conducted a longitudinal analysis on a prospective cohort of COVID-19 patients followed up for >6 months. Neutralizing activity was evaluated using HIV reporter pseudoviruses expressing SARS-CoV-2 S protein. IgG antibody titer was evaluated by ELISA against the S2 subunit, the receptor binding domain (RBD), and the nucleoprotein (NP). Statistical analyses were carried out using mixed-effects models.FindingsWe found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity, which persisted 6 months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a 2-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at 6 months remained higher among hospitalized individuals compared to mild symptomatic. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of anti-RBD, S2, or NP antibody titers, all of them showing a constant decline over the follow-up period.ConclusionsOur results reinforce the hypothesis that the quality of the neutralizing immune response against SARS-CoV-2 evolves over the post-convalescent stage.
| S-EPMC7847406 | biostudies-literature
Project description:The emergence of the Omicron variant has generated concerns about the efficacy of COVID-19 vaccines. We evaluated the serum neutralizing activity of antibodies against the Omicron (lineage BA.1.1) by plaque reduction neutralizing test, as well as its correlation with age and gender, in a Colombian cohort six months after being vaccinated with BNT162b2 (Pfizer/BioNTech). Compared to all other variants analyzed, a significantly lower neutralizing activity (p<0.001) was observed against Omicron. Interestingly, older individuals exhibited lower titers against Omicron than those younger than 40. No statistical differences in neutralizing activity were observed according to gender. Our results showed that two doses of BNT162b2 might not provide robust protection against the Omicron variant over time. It is necessary to consider including changes in the composition of the vaccines to protect against new emerging variants of SARS-CoV-2 and campaigns to implement additional booster vaccinations.
| S-EPMC9811190 | biostudies-literature
Project description:Many murine and non-human primate animal models have been recently developed to understand Zika viral pathogenesis. However, a major limitation with these models is the inability to directly examine the human-specific immune response. Here, we utilized a BLT humanized mouse model endowed with a transplanted human immune system. Plasma viremia could be detected within 48h after viral challenge and viremia persisted for as long as 220 days in some mice. Neutralizing human antibody was detected in infected mice and mouse sera showed reactivity with the viral envelope and capsid proteins in a radio-immunoprecipitation assay. Human monocytes/macrophages, B cells and hematopoietic stem cells in the bone marrow were found to be virus infected. These data establish that BLT mice are permissive for Zika viral infection and are capable of generating viral-specific human immune responses thus providing a human surrogate model for future testing of vaccine and antiviral therapeutic candidates.
| S-EPMC5906046 | biostudies-literature
Project description:Human milk oligosaccharides (HMOs) have specific dose-dependent effects on child health outcomes. The HMO profile differs across mothers and is largely dependent on gene expression of specific transferase enzymes in the lactocytes. This study investigated the trajectories of absolute HMO concentrations at three time points during lactation, using a more accurate, robust, and extensively validated method for HMO quantification. We analyzed human milk sampled at 6 weeks (n = 682), 6 months (n = 448), and 12 months (n = 73) of lactation in a birth cohort study conducted in south Germany, using label-free targeted liquid chromatography mass spectrometry (LC-MS2). We assessed trajectories of HMO concentrations over time and used linear mixed models to explore the effect of secretor status and milk group on these trajectories. Generalized linear model-based analysis was used to examine associations between HMOs measured at 6 weeks of lactation and maternal characteristics. Results: Overall, 74%, 18%, 7%, and 1% of human milk samples were attributed to milk groups I, II, III, and IV, respectively. Most HMO concentrations declined over lactation, but some increased. Cross-sectionally, HMOs presented high variations within milk groups and secretor groups. The trajectories of HMO concentrations during lactation were largely attributed to the milk group and secretor status. None of the other maternal characteristics were associated with the HMO concentrations. The observed changes in the HMO concentrations at different time points during lactation and variations of HMOs between milk groups warrant further investigation of their potential impact on child health outcomes. These results will aid in the evaluation and determination of adequate nutrient intakes, as well as further (or future) investigation of the dose-dependent impact of these biological components on infant and child health outcomes.
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