scholarly journals Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1135
Author(s):  
Benjamin Trinité ◽  
Edwards Pradenas ◽  
Silvia Marfil ◽  
Carla Rovirosa ◽  
Víctor Urrea ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Natural Infection ◽  
Small Reduction ◽  
Neutralizing Activity ◽  
Infection Time ◽  
Cross Neutralization

With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.

scholarly journals Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals.

2021 ◽  
Author(s):  
Benjamin Trinite ◽  
Edwards Pradenas ◽  
Silvia Marfil ◽  
Carla Rovirosa ◽  
Victor Urrea ◽  
...  
Keyword(s):  
Natural Infection ◽  
Neutralizing Activity ◽  
Infection Time ◽  
Cross Neutralization ◽  
Potential Impact

To assess the potential impact of predominant circulating SARS-CoV-2 variants on neutralizing activity of infected and/or vaccinated individuals, we analyzed neutralization of pseudoviruses expressing the spike of the original Wuhan strain, the D614G and B.1.1.7 variants. Our data show that parameters of natural infection (time from infection and infecting variant) determined cross-neutralization. Importantly, upon vaccination, previously infected individuals developed equivalent B.1.1.7 and Wuhan neutralizing responses. In contrast, uninfected vaccinees showed reduced neutralization against B.1.1.7.

scholarly journals Clinical course impacts early kinetics and long-term magnitude and amplitude of SARS-CoV-2 neutralizing antibodies beyond one year after infection

2021 ◽  
Author(s):  
Edwards Pradenas ◽  
Benjamin Trinité ◽  
Víctor Urrea ◽  
Silvia Marfil ◽  
Ferran Tarrés-Freixas ◽  
...  
Keyword(s):  
B Cells ◽  
Neutralizing Antibodies ◽  
Primary Infection ◽  
Natural Infection ◽  
Optimal Strategies ◽  
Longitudinal Models ◽  
Neutralizing Activity ◽  
Cross Neutralization ◽  
One Year

Background: Understanding the determinants of long-term immune responses to SARS-CoV-2 and the concurrent impact of vaccination and emerging variants of concern will guide optimal strategies to achieve global protection against the COVID-19 pandemic. Methods: A prospective cohort of 332 COVID-19 patients was followed beyond one year. Plasma neutralizing activity was evaluated using HIV-based reporter pseudoviruses expressing different SARS-CoV-2 spikes and was longitudinally analyzed using mixed-effects models. Findings: Long-term neutralizing activity was stable beyond one year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while outpatient responses were dominated by long-lived B cells. In both groups, vaccination boosted responses to natural infection, although viral variants, mainly B.1.351, reduced the efficacy of neutralization. Importantly, despite showing higher neutralization titers, hospitalized patients showed lower cross-neutralization of B.1.351 variant compared to outpatients. Multivariate analysis identified severity of primary infection as the factor that independently determines both the magnitude and the inferior cross-neutralization activity of long-term neutralizing responses. Conclusions: Neutralizing response induced by SARS-CoV-2 is heterogeneous in magnitude but stable beyond one year after infection. Vaccination boosts these long-lasting natural neutralizing responses, counteracting the significant resistance to neutralization of new viral variants. Severity of primary infection determines higher magnitude but poorer quality of long-term neutralizing responses.

scholarly journals Antibody Evolution after SARS-CoV-2 mRNA Vaccination

2021 ◽  
Author(s):  
Alice Cho ◽  
Frauke Muecksch ◽  
Dennis Schaefer-Babajew ◽  
Zijun Wang ◽  
Shlomo Finkin ◽  
...  
Keyword(s):  
B Cells ◽  
Severe Acute Respiratory Syndrome ◽  
B Cell ◽  
Natural Infection ◽  
Initial Response ◽  
Memory B Cells ◽  
Neutralizing Activity ◽  
Cell Responses ◽  
One Year ◽  
Over Time

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested. Here, we examine memory B cell evolution 5 months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccines in a cohort of SARS-CoV-2 naive individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge 5 months after vaccination of naive individuals express antibodies that are equivalent to those that dominate the initial response. We conclude that memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines would produce a quantitative increase in plasma neutralizing activity but not the qualitative advantage against variants obtained by vaccinating convalescent individuals.

scholarly journals Cross neutralization of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike

2021 ◽  
Author(s):  
Patrick Wilson ◽  
Siriruk Changrob ◽  
Yanbin Fu ◽  
Jenna Guthmiller ◽  
Peter Halfmann ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Cross Neutralization

Abstract Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484 and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and the variants of concern, including B.1.1.7 (alpha), P.1 (gamma) and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to wildtype (WT) SARS-CoV-2 do possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern.

scholarly journals Thromboses and Hemostasis Disorders Associated with Coronavirus Disease 2019: The Possible Causal Role of Cross-Reactivity and Immunological Imprinting

2021 ◽  
Author(s):  
Darja Kanduc
Keyword(s):  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Natural Infection ◽  
Vascular Diseases ◽  
Cross Reactivity ◽  
Active Immunization ◽  
Thromboembolic Complications ◽  
Human Proteins ◽  
Almost All

AbstractBy examining the issue of the thromboses and hemostasis disorders associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) through the lens of cross-reactivity, it was found that 60 pentapeptides are shared by SARS-CoV-2 spike glycoprotein (gp) and human proteins that— when altered, mutated, deficient or, however, improperly functioning— cause vascular diseases, thromboembolic complications, venous thrombosis, thrombocytopenia, coagulopathies, and bleeding, inter alia. The peptide commonality has a relevant immunological potential as almost all of the shared sequences are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes, thus supporting the possibility of cross-reactions between the viral gp and the thromboses-related human proteins. Moreover, many of the shared peptide sequences are also present in pathogens to which individuals have previously been exposed following natural infection or vaccinal routes, and of which the immune system has stored imprint. Such an immunological memory might rapidly trigger anamnestic secondary cross-reactive responses of extreme affinity and avidity, in this way explaining the thromboembolic adverse events that can associate with SARS-CoV-2 infection or active immunization.

scholarly journals Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1347
Author(s):  
Claudia Maria Trombetta ◽  
Serena Marchi ◽  
Simonetta Viviani ◽  
Alessandro Manenti ◽  
Linda Benincasa ◽  
...  
Keyword(s):  
Natural Infection ◽  
Neutralizing Antibody ◽  
Original Strain ◽  
Immune Protection ◽  
Serum Samples ◽  
Symptomatic Infection ◽  
Neutralizing Activity ◽  
The United Kingdom ◽  
Antibody Titers ◽  
Pandemic Wave

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

scholarly journals Delayed neutralizing antibody response in the acute phase correlates with severe progression of COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hitoshi Kawasuji ◽  
Yoshitomo Morinaga ◽  
Hideki Tani ◽  
Miyuki Kimura ◽  
Hiroshi Yamada ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Pseudotyped Virus ◽  
Serum Samples ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Time Points ◽  
Moderate Disease ◽  
Activity Dynamics

AbstractAdaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

scholarly journals Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiandan Xiang ◽  
Boyun Liang ◽  
Yaohui Fang ◽  
Sihong Lu ◽  
Sumeng Li ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Protein S ◽  
Igg Antibodies ◽  
Neutralizing Activity ◽  
Specific Igg ◽  
One Year ◽  
Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers in Convalescent Plasma and Recipients in New Mexico: An Open Treatment Study in Patients With Coronavirus Disease 2019

2020 ◽  
Vol 222 (10) ◽  
pp. 1620-1628 ◽  
Author(s):  
Steven B Bradfute ◽  
Ivy Hurwitz ◽  
Alexandra V Yingling ◽  
Chunyan Ye ◽  
Qiuying Cheng ◽  
...  
Keyword(s):  
New Mexico ◽  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibody ◽  
Traditional Food ◽  
Neutralizing Activity ◽  
Time Points ◽  
Before And After ◽  
Open Treatment ◽  
Antibody Titers ◽  
Donor Plasma

Abstract Background Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway. Methods We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Results NAb titers in the donor CP units were low (<1:40 to 1:160) and had no effect on recipient neutralizing activity 1 day after transfusion. NAb titers were detected in 6 of 12 patients on enrollment and in 11 of 12 at ≥2 time points. Average titers peaked on day 7 and declined toward day 14 (P = .004). Nab titers and immunoglobulin G levels were correlated in donor plasma units (ρ = 0.938; P < .001) and in the cumulative patient measures (ρ = 0.781; P < .001). Conclusions CP infusion did not alter recipient NAb titers. Prescreening of CP may be necessary for selecting donors with high titers of neutralizing activity for infusion into patients with COVID-19. Clinical Trials Registration NCT04434131.

scholarly journals Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

2021 ◽  
Author(s):  
Carlos A Sariol ◽  
Petraleigh Pantoja ◽  
Crisanta Serrano-Collazo ◽  
Tiffant Rosa-Arocho ◽  
Albersy Armina ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Viral Neutralization ◽  
Neutralizing Activity ◽  
Robust Immune Response

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

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