Higher correlation between neutralizing antibodies and surrogate neutralizing or binding antibodies in COVID-19 patients than vaccine recipients
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ABSTRACT:
SUBMITTER: Lerdsamran H
PROVIDER: S-EPMC11020499 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:The evaluation of the neutralizing capacity of anti-SARS-CoV-2 antibodies is important because they represent real protective immunity. In this study we aimed to measure and compare the neutralizing antibodies (NAbs) in COVID-19 patients and in vaccinated individuals. One-hundred and fifty long-term samples from 75 COVID-19 patients were analyzed with a surrogate virus neutralization test (sVNT) and compared to six different SARS-CoV-2 serology assays. The agreement between the sVNT and pseudovirus VNT (pVNT) results was found to be excellent (i.e., 97.2%). The NAb response was also assessed in 90 individuals who had received the complete dose regimen of BNT162b2. In COVID-19 patients, a stronger response was observed in moderate-severe versus mild patients (p-value = 0.0006). A slow decay in NAbs was noted in samples for up to 300 days after diagnosis, especially in moderate-severe patients (r = -0.35, p-value = 0.03). In the vaccinated population, 83.3% of COVID-19-naive individuals had positive NAbs 14 days after the first dose and all were positive 7 days after the second dose, i.e., at day 28. In previously infected individuals, all were already positive for NAbs at day 14. At each time point, a stronger response was observed for previously infected individuals (p-value < 0.05). The NAb response remained stable for up to 56 days in all participants. Vaccinated participants had significantly higher NAb titers compared to COVID patients. In previously infected vaccine recipients, one dose might be sufficient to generate sufficient neutralizing antibodies.
| S-EPMC8309994 | biostudies-literature
Project description: Not available
| S-EPMC9850840 | biostudies-literature
Project description:Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare autoimmune condition associated with recombinant adenovirus (rAV)-based COVID-19 vaccines. It is thought to arise from autoantibodies targeting platelet factor 4 (aPF4), triggered by vaccine-induced inflammation and the formation of neo-antigenic complexes between PF4 and the rAV vector. To investigate the specific induction of aPF4 by rAV-based vaccines, we examined sera from rAV vaccine recipients (AZD1222, AD26.COV2.S) and messenger RNA (mRNA) based (mRNA-1273, BNT162b2) COVID-19 vaccine recipients. We compared the antibody fold change (FC) for aPF4 and for antiphospholipid antibodies (aPL) of rAV to mRNA vaccine recipients. We combined two biobanks of Dutch healthcare workers and matched rAV-vaccinated individuals to mRNA-vaccinated controls, based on age, sex and prior history of COVID-19 (AZD1222: 37, Ad26.COV2.S: 35, mRNA-1273: 47, BNT162b2: 26). We found no significant differences in aPF4 FCs after the first (0.99 vs. 1.08, mean difference (MD) = -0.11 (95% CI -0.23 to 0.057)) and second doses of AZD1222 (0.99 vs. 1.10, MD = -0.11 (95% CI -0.31 to 0.10)) and after a single dose of Ad26.COV2.S compared to mRNA-based vaccines (1.01 vs. 0.99, MD = 0.026 (95% CI -0.13 to 0.18)). The mean FCs for the aPL in rAV-based vaccine recipients were similar to those in mRNA-based vaccines. No correlation was observed between post-vaccination aPF4 levels and vaccine type (mean aPF difference -0.070 (95% CI -0.14 to 0.002) mRNA vs. rAV). In summary, our study indicates that rAV and mRNA-based COVID-19 vaccines do not substantially elevate aPF4 levels in healthy individuals.
| S-EPMC10747426 | biostudies-literature
Project description:Background While evaluating COVID-19 vaccine responses using a rapid neutralizing antibody (NAb) test, we observed that 25% of mRNA vaccine recipients did not neutralize >50%. We termed this group “vaccine poor responders” (VPRs). The objective of this study was to determine if individuals who neutralized <50% would remain VPRs, or if a third dose would elicit high levels of NAbs. Methods 269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines were evaluated. NAb levels were measured: (i) 2–4 weeks after a second vaccine dose, (ii) 2–4 months after the second dose, (iii) within 1–2 weeks prior to a third dose and (iv) 2–4 weeks after a third mRNA vaccine dose. Results Analysis of vaccine recipients reveals that 25% did not neutralize above 50% (Median neutralization = 21%, titers <1:80) within a month after their second dose. Twenty-three of these VPRs obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1–8 months (average = 5 months) after their second dose. Within a month after their third dose, VPRs show an average 5.4-fold increase in NAb levels (range: 46–99%). Conclusions The results suggest that VPRs are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose. Although it is not known what levels of NAbs protect from infection or disease, those in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, and potential transmission. Plain language summary Neutralizing antibodies are proteins used by the immune system to respond to viruses and other infectious agents. Vaccination against COVID-19 induces production of neutralizing antibodies that stop virus from infecting cells. We measured levels of neutralizing antibodies in a drop of blood after 2 doses of vaccines distributed by Pfizer and BioNTech or Moderna (COMIRNATY and Spikevax). Twenty-five percent of vaccine recipients did not make high levels of neutralizing antibodies. After receiving a third dose of vaccine, most of these vaccine recipients made high levels of neutralizing antibodies. Our data suggest a third dose is important for vaccine recipients that did not generate high neutralizing antibody levels after 2 doses of vaccine and thus might be an important component of a successful vaccination strategy. Lake, Roeder et al. measured neutralizing antibody responses after 2 and 3 doses of mRNA COVID vaccination. Recipients who did not generate strong neutralizing antibody responses after 2 vaccine doses were found to have high levels of neutralizing antibodies after a third vaccine dose.
| S-EPMC9273613 | biostudies-literature
Project description:To effectively control and prevent the pandemic of coronavirus disease 2019 (COVID-19), suitable vaccines have been researched and developed rapidly. Currently, 31 COVID-19 vaccines have been approved for emergency use or authorized for conditional marketing, with more than 9.3 billion doses of vaccines being administered globally. However, the continuous emergence of variants with high transmissibility and an ability to escape the immune responses elicited by vaccines poses severe challenges to the effectiveness of approved vaccines. Hundreds of new COVID-19 vaccines based on different technology platforms are in need of a quick evaluation for their efficiencies. Selection and enrollment of a suitable sample of population for conducting these clinical trials is often challenging because the pandemic so widespread and also due to large scale vaccination. To overcome these hurdles, methods of evaluation of vaccine efficiency based on establishment of surrogate endpoints could expedite the further research and development of vaccines. In this review, we have summarized the studies on neutralizing antibody responses and effectiveness of the various COVID-19 vaccines. Using this data we have analyzed the feasibility of establishing surrogate endpoints for evaluating the efficacy of vaccines based on neutralizing antibody titers. The considerations discussed here open up new avenues for devising novel approaches and strategies for the research and develop as well as application of COVID-19 vaccines.
| S-EPMC9092276 | biostudies-literature
Project description: Not available
| S-EPMC7586990 | biostudies-literature
Project description:The COVID-19 pandemic caused by SARS-CoV-2 has led to hundreds of millions of infections and millions of deaths, however, human monoclonal antibodies (mAbs) can be an effective treatment. Since SARS-CoV-2 emerged, a variety of strains have acquired increasing numbers of mutations to gain increased transmissibility and escape from the immune response. Most reported neutralizing human mAbs, including all approved therapeutic ones, have been knocked down or out by these mutations. Broadly neutralizing mAbs are therefore of great value, to treat current and possible future variants. Here, we review four types of neutralizing mAbs against the spike protein with broad potency against previously and currently circulating variants. These mAbs target the receptor-binding domain, the subdomain 1, the stem helix, or the fusion peptide. Understanding how these mAbs retain potency in the face of mutational change could guide future development of therapeutic antibodies and vaccines.
| S-EPMC10301462 | biostudies-literature
Project description:BackgroundMorbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease.MethodsWe performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available.ResultsThere were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak.ConclusionsBamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19.
| S-EPMC8967616 | biostudies-literature
Project description:BackgroundHighly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses, warranting continued immune-monitoring.MethodsWe used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions.FindingsWe tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible.InterpretationTaken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity.FundingThis work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003.
| S-EPMC8527879 | biostudies-literature
Project description:To assess the factors that influencing the persistence of virus neutralizing antibody (VNA), and to establish prediction models to provide the appropriate timing for booster administration, a cohort of post-exposure rabies vaccine recipients was investigated. The VNA determined records from 2019 to 2023 and interrelated factors were analyzed, including gender, age, rabies immunoglobulin (RIG) administration, vaccine products, vaccination schedule, and vaccination intervals etc. The geometric mean of VNA titre within 1 month after primary vaccination with 2-1-1 schedule was statistically higher than that with 5-dose course (P = 0.031). The interaction between exposure and vaccination schedule was observed on primary vaccination, which showed that a decrease of 19.74 % (95 % CI: 5.99%-64.95 %, P = 0.008) of VNA titre among vaccinee with 5-dose and exposure III. Individuals with RIG administration produced lower VNA titres than those without RIG administration (P = 0.001). Vaccine products (Chengda, P = 0.015; human diploid cell, P = 0.026) and re-exposed time (P = 0.000) exhibited independent effects following booster vaccination. Based on the prediction model, the 99 % individual prediction intervals (IPI) of VNA titres were established at 3, 6, 12 and 18 months for the 12 characteristic populations respectively. The cases of VNA below 0.5 IU/ml first appeared at 6 months in group D of primary vaccinations and at 10 years in group F of boosters. We conclude that for primary vaccination 2-1-1 schedule is more efficient than 5-dose; the use of residual rabies immunoglobulin for distal intramuscular injection isn't recommended. The 99 % IPI of VNA titres could provide the appropriate timing for booster vaccination.
| S-EPMC11336818 | biostudies-literature