Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals.
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ABSTRACT:
SUBMITTER: Maeda K
PROVIDER: S-EPMC8613264 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the features of immune response remain to be clarified. In the present prospective observational study, 225 healthy individuals in Kumamoto General Hospital, Japan, who received two BNT162b2 doses in February 2021, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT 50 ; assessed using infectious virions and live target cells) with SARS-CoV-2-S1-binding-IgG and -IgM levels, adverse effects (AEs), ages, and genders were examined. The average half-life of neutralizing activity and the average time length for the loss of detectable neutralizing activity were determined and the potency of serums against variants of concerns was also determined. Significant rise in NT 50 s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT 50 s and ages, but no correlation was seen between NT 50 s and AEs. NT 50 s and IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of neutralizing activity in the vaccinees was approximately 67.8 days and the average time length for their serums to lose the detectable neutralizing activity was 198.3 days. While serums from elite-responders (NT 50 s>1,500-fold: the top 4% among all participants' NT 50 s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT 50 s failed to block the infectivity of a beta strain. BNT162b2-elicited immune response has no significant association with AEs. BNT162b2-efficacy is likely diminished to under detection limit by 6-7 months post-1st shot. High-level neutralizing antibody-containing serums potently to moderately block the infection of SARS-CoV-2 variants; however, a few moderate-level neutralizing antibody-containing serums failed to do so. If BNT162b2-elicited immunity memory is short, an additional vaccine or other protective measures would be needed. Evidence before this study: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the salient features of immune response including the persistence of protection remain to be clarified. There is a report that anti-SARS-CoV-2 antibodies persist through 6 months after the second dose of mRNA-1273 vaccine (Doria-Rose et al. N Engl J Med . 2021;384:2259-2261); however, more definite immune kinetics following mRNA-vaccine-elicited protection have to be clarified. The mRNA-vaccine-elicited protection against SARS-CoV-2 variants are also to be determined. Added value of this study: In the present prospective study, 225 twice-BNT162b2-dose-receiving individuals in Japan were enrolled. No significant correlation was seen between 50% neutralizing titers (NT 50 s), determined by using infectious SARS-CoV-2 virions and live target cells, and adverse effects. Largely, NT 50 s and IgG levels were greater in women than in men. Following 28 days post-2 nd shot, significant reduction was seen in NT 50 s, IgG, and IgM levels. The average half-life of NT 50 s was ∼68 days and the average time-length for participants' serums to lose the detectable activity was ∼198 days. Although serums from elite-responders potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT 50 s failed to block the infectivity of a beta strain. Implications of all the available evidence: BNT162b2 efficacy is likely to be diminished to under detection limit by 6-7 months post-1 st shot on average. Individuals with moderate NT 50 s may fail to block beta variants. If BNT162b2-elicited immune memory is lost soon, additional vaccine(s) or other protective means would be needed.
| S-EPMC8351777 | biostudies-literature
Project description:Global surveillance programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are showing the emergence of variants with mutations in the spike protein. Genomic and laboratory surveillance are important to determine if these variants may be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated: Mu, a variant of interest; Gamma, a variant of concern; B.1.111, which lacks genetic markers associated with greater virulence. Microneutralization assays were performed by incubating 120 mean tissue culture infectious doses (TCID50) of each SARS-CoV-2 isolate with five two-fold serial dilutions of sera from 31 BNT162b2-vaccinated volunteers. The mean neutralization titer (MN50) was calculated by the Reed-Muench method. At the end of August, Mu represented 49% of coronavirus disease 2019 (COVID-19) cases in Colombia, followed by 25% of Gamma. In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162b2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. This study shows the importance of continuing surveillance programs of emerging variants, as well as the need to evaluate the neutralizing antibody response induced by other vaccines.
| S-EPMC8876570 | biostudies-literature
Project description:The reduced vaccine efficacy against the SARS-CoV-2 variant lineage B. 1.351 (beta variant) containing the E484K and N501Y mutations is well known. The E484K mutation in SARS-CoV-2 is thought to be responsible for weakened humoral immunity. Vaccine efficacy against the R.1 lineage, which contains the E484K mutation but not the N501Y mutation, is uncertain. Serum samples were collected from 100 healthy Japanese participants three weeks after receiving the second dose of the BNT162b2 vaccine, and serum neutralization antibody titers were measured against five SARS-CoV-2 variants. The geometric mean neutralization titers measured for the original and R.1 lineages were equivalent (91.90 ± 2.40 and 102.67 ± 2.28, respectively), whereas a low titer was measured for the beta variant (18.03 ± 1.92). Although further investigations with other variant strains and serum samples are essential, our results imply that the weakened humoral response is not caused solely by the E484K mutation. (UMIN000043340).
| S-EPMC8841208 | biostudies-literature
Project description:Understanding antibody-based SARS-CoV-2 immunity is critical for overcoming the COVID-19 pandemic and informing vaccination strategies. We evaluated SARS-CoV-2 antibody dynamics over 10 months in 963 individuals who predominantly experienced mild COVID-19. Investigating 2,146 samples, we initially detected SARS-CoV-2 antibodies in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of individuals demonstrated exceptional SARS-CoV-2 neutralization, with these "elite neutralizers" also possessing SARS-CoV-1 cross-neutralizing IgG. Multivariate statistical modeling revealed age, symptomatic infection, disease severity, and gender as key factors predicting SARS-CoV-2-neutralizing activity. A loss of reactivity to the virus spike protein was observed in 13% of individuals 10 months after infection. Neutralizing activity had half-lives of 14.7 weeks in serum versus 31.4 weeks in purified IgG, indicating a rather long-term IgG antibody response. Our results demonstrate a broad spectrum in the initial SARS-CoV-2-neutralizing antibody response, with sustained antibodies in most individuals for 10 months after mild COVID-19.
| S-EPMC8090990 | biostudies-literature
Project description:Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concern (VoC)s. That is why the measure of the protection conferred by vaccination cannot solely rely on the antibody levels, but also requires to measure their neutralization capacity. Here we used a mathematical model to follow the humoral response in 26 individuals that received up to three vaccination doses of Bnt162b2 vaccine, and for whom both anti-S IgG and neutralization capacity was measured longitudinally against all main VoCs. Our model could identify two independent mechanisms that led to a marked increase in measured humoral response over the successive vaccination doses. In addition to the already known increase in IgG levels after each dose, we identified that the neutralization capacity was significantly increased after the third vaccine administration against all VoCs, despite large inter-individual variability. Consequently, the model projects that the mean duration of detectable neutralizing capacity against non-Omicron VoC is between 348 days (Beta variant, 95% Prediction Intervals PI [307; 389]) and 587 days (Alpha variant, 95% PI [537; 636]). Despite the low neutralization levels after three doses, the mean duration of detectable neutralizing capacity against Omicron variants varies between 173 days (BA.5 variant, 95% PI [142; 200]) and 256 days (BA.1 variant, 95% PI [227; 286]). Our model shows the benefit of incorporating the neutralization capacity in the follow-up of patients to better inform on their level of protection against the different SARS-CoV-2 variants. Trial registration: This clinical trial is registered with ClinicalTrials.gov, Trial IDs NCT04750720 and NCT05315583.
| S-EPMC10434962 | biostudies-literature
Project description:Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021-000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1 .
| S-EPMC8822735 | biostudies-literature
Project description:Each severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant renews concerns about decreased vaccine neutralization weakening efficacy. However, while prevention of infection varies, protection from disease remains and implicates immunity beyond neutralization in vaccine efficacy. Polyclonal antibodies function through Fab domains that neutralize virus and Fc domains that induce non-neutralizing responses via engagement of Fc receptors on immune cells. To understand how vaccines promote protection, we leverage sera from 51 SARS-CoV-2 uninfected individuals after two doses of the BNT162b2 mRNA vaccine. We show that neutralizing activities against clinical isolates of wild-type and five SARS-CoV-2 variants, including Omicron BA.2, link to FcγRIIIa/CD16 non-neutralizing effector functions. This is associated with post-translational afucosylation and sialylation of vaccine-specific antibodies. Further, polyfunctional neutralizing and non-neutralizing breadth, magnitude, and coordination diminish with age. Thus, studying Fc functions in addition to Fab-mediated neutralization provides greater insight into vaccine efficacy for vulnerable populations, such as the elderly, against SARS-CoV-2 and novel variants.
| S-EPMC9533669 | biostudies-literature
Project description:We evaluated the post-booster (BNT162b2) antibody responses in Singapore. Participants (n = 43) were tested pre-booster and 20/30/60/90 days post-booster. Participants were boosted 120-240 days (mean 214 days) after their second dose and had no history or serologic evidence of prior COVID-19 infection; all participants had undetectable SARS-CoV-2 nucleocapsid antibodies throughout the study. Total nucleocapsid and spike antibodies (S-Ab) were assessed on the Roche Elecsys e802 and neutralizing antibody (N-Ab) on the Snibe quantitative N-Ab assay. Pre-booster median S-Ab/N-Ab titers were 829 BAU/mL/0.83 µg/mL; 2 participants were below manufacturer's N-Ab cut-offs of 0.3 µg/mL (0.192 and 0.229). Both S-Ab and N-Ab titers peaked at 30 days post-booster (median S-Ab 25,220 BAU/mL and N-Ab 30.3 µg/mL) at 30-37× pre-booster median levels. These peak post-booster S-Ab/N-Ab titers were 11× (25,220 vs. 2235 BAU/mL) and 9× (30.3 vs. 3.52 µg/mL) higher than the previously reported peak post-second dose levels. Antibody titers declined to 12,315 BAU/mL (51% decrease) and 14.3 µg/mL (53% decrease) 90 days post-booster. Non-linear regression estimates for S-Ab/N-Ab half-lives were 44/58 days. At 180 days post-booster, S-Ab/N-Ab are estimated to be 2671 BAU/mL/4.83 µg/mL. Both S-Ab and N-Ab show a good response following post-booster vaccination, with half-lives that may provide a prolonged antibody response.
| S-EPMC8879250 | biostudies-literature
Project description:ImportanceData are limited on whether patients with breakthrough COVID-19 infection have the potential to significantly contribute to the spread of SARS-CoV-2.ObjectiveTo compare the secondary attack rate and infectious viral shedding kinetics of SARS-CoV-2 between fully vaccinated individuals (breakthrough infection group) and partially or unvaccinated individuals (nonbreakthrough infection group).Design, setting, and participantsThis cohort study assessed secondary transmission by analyzing the epidemiologic data of health care workers, inpatients, and caregivers diagnosed with COVID-19 during hospitalization or residence in a tertiary care hospital between March 1, 2020, and November 6, 2021. To evaluate viral shedding kinetics, the genomic RNA of SARS-CoV-2 was measured using polymerase chain reaction and performed virus culture from daily saliva samples of individuals with mild COVID-19 infected with the Delta variant who were isolated in a community facility in Seoul, South Korea, between July 20 and August 20, 2021.ExposuresCOVID-19 vaccination.Main outcomes and measuresThe secondary attack rate and infectious viral shedding kinetics according to COVID-19 vaccination status.ResultsA total of 173 individuals (median [IQR] age, 47 [32-59] years; 100 female [58%]) with COVID-19 were included in the secondary transmission study, of whom 50 (29%) had a breakthrough infection. Secondary transmission was significantly less common in the breakthrough infection group than in the nonbreakthrough infection group (3 of 43 [7%] vs 29 of 110 [26%]; P = .008). In the viral shedding kinetics study, 45 patients (median age, 37 years [IQR, 25-49 years]; 14 female [31%]) infected with the Delta variant were included, of whom 6 (13%) were fully vaccinated and 39 (87%) were partially or unvaccinated. Although the initial genomic viral load was comparable between the 2 groups, viable virus in cell culture was detected for a notably longer duration in partially vaccinated (8 days after symptom onset) or unvaccinated (10 days after symptom onset) individuals compared with fully vaccinated individuals (4 days after symptom onset).Conclusions and relevanceIn this cohort study, although the initial genomic viral load was similar between vaccinated and unvaccinated individuals, fully vaccinated individuals had a shorter duration of viable viral shedding and a lower secondary attack rate than partially vaccinated or unvaccinated individuals. Data from this study provide important evidence that despite the possibility of breakthrough infections, COVID-19 vaccinations remain critically useful for controlling the spread of SARS-CoV-2.
| S-EPMC9131744 | biostudies-literature
Project description:BackgroundPatients with multiple sclerosis (pwMS) are often treated with disease modifying therapies (DMT) with immunomodulatory effects. This is of particular concern following the development of several vaccines to combat coronavirus disease 19 (COVD-19), a potentially fatal illness caused by SARS-CoV-2.ObjectivesTo determine the efficacy of SARS-CoV-2 vaccination in pwMS and the impact of disease modifying therapies (DMT) on vaccine response.MethodsThis is a prospective longitudinal study in pwMS. Longitudinal serum samples were obtained prior to, and after SARS-CoV-2 mRNA vaccination. A novel neutralizing antibody (nAb) assay was used to determine nAbs titres against SARS-CoV-2 spike.ResultsWe observed that (1) pwMS on B-cell depleting therapies exhibited reduced response to vaccination compared to other pwMS, correlating with time from last anti-CD20 infusion, (2) prior COVID-19 illness, DMT category, and pyramidal function were significant predictors of vaccine responsiveness, and (3) circulating absolute lymphocyte count (ALC) and IgG levels correlated with nAb levels.ConclusionsWe demonstrate that pwMS exhibit reduced nAb response to mRNA vaccination dependent on DMT status and identify predictive biomarkers for vaccine efficacy. We conclude that additional vaccination strategies may be necessary to achieve protective immunity in pwMS.
| S-EPMC8941285 | biostudies-literature