scholarly journals Superior immunity that allows neutralization of all SARS-CoV-2 variants of concern develops in COVID-19 convalescents and naïve individuals after three vaccinations

2022 ◽  
Author(s):  
Ulrike Protzer ◽  
Paul Wratil ◽  
Marcel Stern ◽  
Alina Priller ◽  
Annika Willmann ◽  
...  
Keyword(s):  
Immune Escape ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immune Protection ◽  
Breakthrough Infection ◽  
High Quality ◽  
Antibody Avidity ◽  
Neutralization Capacity ◽  
Neutralizing Capacity ◽  
Antibody Dynamics

Abstract Infection-neutralizing antibody responses after SARS-CoV-2 infection or COVID-19 vaccination are an essential part of antiviral immunity. This immune protection is challenged by the occurrence of SARS-CoV-2 variants of concern (VoCs) with immune escape properties, such as omicron (B.1.1.529) that is rapidly spreading worldwide. Here, we report neutralizing antibody dynamics in a longitudinal cohort of COVID-19 convalescent and naïve individuals vaccinated with mRNA BNT162b2 by quantifying anti-SARS-CoV-2-spike antibodies and determining their avidity and neutralization capacity. A superior infection-neutralizing capacity against all VoCs, including omicron, developed by either two vaccinations of convalescents, or a third vaccination or breakthrough infection of twice-vaccinated naïve individuals. These three consecutive spike antigen exposures resulted in an increasing neutralization capacity per anti-spike antibody unit and were paralleled by stepwise increases in antibody avidity. In conclusion, an infection/vaccination-induced hybrid immunity or a triple immunization induces high-quality antibodies resulting in superior neutralization capacity against VoCs, including omicron.

scholarly journals Probing neutralizing-antibody responses against emerging measles viruses (MVs): immune selection of MV by H protein-specific antibodies?

2005 ◽  
Vol 86 (2) ◽  
pp. 365-374 ◽  
Author(s):  
Sabine Santibanez ◽  
Stefan Niewiesk ◽  
Alla Heider ◽  
Jürgen Schneider-Schaulies ◽  
Guy A. M. Berbers ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Neutralizing Capacity ◽  
Human Sera ◽  
H Protein ◽  
Neutralizing Epitopes ◽  
Selection Of

Measles virus (MV) infection and vaccination induce long-lasting immunity and neutralizing-antibody responses that are directed against the MV haemagglutinin (H) and the fusion (F) protein. A new MV genotype, D7, emerged recently in western Germany and rapidly replaced the long-term endemically circulating genotypes C2 and D6. Analysis of the H gene of C2, D6, D7 and vaccine viruses revealed uniform sequences for each genotype. Interestingly, a consistent exchange of seven distinct amino acids in the D7 H was observed when compared with residues shared between C2, D6 and vaccine viruses, and one exchange (D416→N) in the D7 H was associated with an additional N-linked glycosylation. In contrast, the F gene is highly conserved between MVs of these genotypes. To test whether the D7 H protein escapes from antibody responses that were raised against earlier circulating or vaccine viruses, the neutralizing capacity of mAbs recognizing seven distinct domains on the H of an Edmonston-related MV was compared. The mAbs revealed a selective and complete loss of two neutralizing epitopes on the D7 H when compared with C2, D6 and vaccine viruses. To assess whether these alterations of the D7 H affect the neutralizing capacity of polyclonal B-cell responses, genotype-specific antisera were produced in cotton rats. However, no significant genotype-dependent difference was found. Likewise, human sera obtained from vaccinees (n=7) and convalescents (n=6) did not distinguish between the MV genotypes. Although the hypothesis of selection of D7 viruses by pre-existing neutralizing antibodies is compatible with the differing pattern of neutralizing epitopes on the H protein, it was not confirmed by the results of MV neutralization with polyclonal sera.

scholarly journals Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background

2008 ◽  
Vol 15 (7) ◽  
pp. 1115-1123 ◽  
Author(s):  
Nareen Abboud ◽  
Arturo Casadevall
Keyword(s):  
Bacillus Anthracis ◽  
Antibody Titer ◽  
Genetic Background ◽  
Protective Antigen ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Full Length ◽  
Mouse Strains ◽  
Neutralizing Capacity ◽  
Antibody Titers

ABSTRACT Neutralizing antibodies to Bacillus anthracis protective antigen (PA), a component of anthrax toxin, mediate protection against anthrax. PA is antigenically complex and can elicit protective and nonprotective antibodies. Furthermore, vaccinated individuals demonstrate considerable variability in their antibody responses to PA. To explore the relationship between PA structure and antigenicity, we produced Escherichia coli strains expressing full-length PA (PA1-4), domains 2 to 4 (PA2-4), domain 1, (PA1), and domain 4 (PA4) and evaluated the immunogenicities and protective efficacies of the protein fractions in four mouse strains (strains A/J, BALB/c, C57BL/6, and Swiss Webster). Immunization with PA1-4 resulted in significantly higher lethal toxin-neutralizing antibody titers than immunization with any recombinant protein (rPA) fraction of PA. The magnitude and neutralizing capacity of the antibody response to full-length PA and its fragments varied depending on the mouse strain. We found no correlation between the antibody titer and the neutralizing antibody titer for A/J and Swiss Webster mice. In C57BL/6 mice, antibody titers and neutralization capacity correlated for two of four rPA domain proteins tested, while BALB/c mice displayed a similar correlation with only one rPA. By correlating the reactivity of immune sera with solvent-exposed linear peptide segments of PA, we tentatively assign the presence of four new linear B-cell epitopes in PA amino acids 121 to 150, 143 to 158, 339 to 359, and 421 to 440. We conclude that the genetic background of the host determines the relative efficacy of the antitoxin response. The results suggest that the variability observed in vaccination studies with PA-derived vaccines is a result of host heterogeneity and implies a need to develop other antigens as vaccine candidates.

scholarly journals BNT162b2 boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19

2021 ◽  
Author(s):  
Georg Behrens ◽  
Joana Barros-Martins ◽  
Anne Cossmann ◽  
Gema Morillas Ramos ◽  
Metodi Stankov ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Large Scale ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immune Protection ◽  
Cell Immunity ◽  
The Impact ◽  
As Effects

Abstract Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity, and large scale second booster vaccination is ongoing. However, data comparing declining immunity after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. We longitudinally monitored immunity in ChAd/ChAd (n=41) and ChAd/BNT (n=88) vaccinated individuals and assessed the impact of a second booster with BNT in both groups. The second booster greatly augmented waning anti-spike IgG but only moderately increased spike-specific CD4+ and CD8+ T cells in both groups to cell frequencies already present after the boost. More importantly, the second booster efficiently restored neutralizing antibody responses against Alpha, Beta, Gamma, and Delta, but neutralizing activity against B.1.1.529 (Omicron) stayed severely impaired. Our data suggest that inferior SARS-CoV-2 specific immune responses after homologous ChAd/ChAd vaccination can be cured by a heterologous BNT vaccination. However, prior heterologous ChAd/BNT vaccination provides no additional benefit for spike-specific T cell immunity or neutralizing Omicron after the second boost.

scholarly journals Kinetics of antibody responses dictate COVID-19 outcome

2020 ◽  
Author(s):  
Carolina Lucas ◽  
Jon Klein ◽  
Maria Sundaram ◽  
Feimei Liu ◽  
Patrick Wong ◽  
...  
Keyword(s):  
Disease Severity ◽  
Disease Onset ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Delayed Response ◽  
Viral Control ◽  
Cross Sectional ◽  
Neutralization Capacity ◽  
Kinetics Of

SummaryRecent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While high anti-S IgG levels correlated with worse disease severity, such correlation was time-dependent. Deceased patients did not have higher overall humoral response than live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se, but rather with the delayed kinetics of NAb production.

scholarly journals Temporal Increase in Neutralization Potency of SARS-CoV-2 Antibodies and Reduced Viral Variant Escape after Sputnik V Vaccination

2021 ◽  
Author(s):  
María M. Gonzalez Lopez Ledesma ◽  
Lautaro Sanchez ◽  
Diego S. Ojeda ◽  
Santiago Oviedo Rouco ◽  
Andres H. Rossi ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Viral Escape ◽  
Similar Process ◽  
Serum Samples ◽  
Viral Variant ◽  
Antibody Maturation ◽  
Neutralizing Capacity ◽  
Alpha Beta ◽  
Over Time

ABSTRACTRecent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we observed a similar process after Sputnik V vaccination. We examined the longitudinal antibody responses and viral neutralizing capacity to variants of concern (VOCs: Alpha, Beta, Gamma, and Delta) and a broadly spread variant of interest (VOI: Lambda) in volunteers up to 6 months after receiving the Sputnik V vaccine in Argentina. A collection of 1,800 serum samples obtained between January and August 2021 was used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing potency to the first-wave linages of SARS-CoV-2 and VOC increases within four months of vaccination, suggesting that antibody maturation occurs. This increase was more evident for the Beta and Gamma variants, which showed the highest propensity for neutralization escape. Our observations suggest that protection increases over the six months following vaccination as a consequence of antibody maturation, resulting in improved potency of antibodies to viral escape mutations.

scholarly journals Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections

2020 ◽  
Author(s):  
Qing Lei ◽  
Yang Li ◽  
Hongyan Hou ◽  
Feng Wang ◽  
Yandi Zhang ◽  
...  
Keyword(s):  
Humoral Immunity ◽  
Exposure Time ◽  
Disease Transmission ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Pseudotyped Virus ◽  
Serological Tests ◽  
Asymptomatic Individuals ◽  
Antibody Dynamics

Abstract Importance Asymptomatic COVID-19 infections have a long duration of viral shedding and contribute substantially to disease transmission. However, the missing asymptomatic cases have been significantly overlooked because of imperfect sensitivity of nucleic acid testing. We aimed to investigate the humoral immunity in asymptomatics, which will help us develop serological tests and improve early identification, understand the humoral immunity to COVID-19, and provide more rational control strategies for the pandemic. Objective To better control the pandemic of COVID-19, dynamics of IgM and IgG responses to 23 proteins of SARS-CoV-2 and neutralizing antibody in asymptomatic COVID-19 infections after exposure time were investigated. Design, setting, and participants 63 asymptomatic individuals were screened by RT-qPCR and ELISA for IgM and IgG from 11,776 personnel returning to work, and close contacts with the confirmed cases in different communities of Wuhan by investigation of clusters and tracing infectious sources. 63 healthy contacts with both negative results for NAT and antibodies were selected as negative controls. 51 mild patients without any preexisting conditions were also screened as controls from 1056 patients during hospitalization in Tongji Hospital. A total of 177 participants were enrolled in this study and serial serum samples (n=213) were collected. The research was conducted between 17 February 2020 and 28 April 2020. Serum IgM and IgG profiles of 177 participants were further probed using a SARS-CoV-2 proteome microarray. Neutralizing antibody responses in different population were detected by a pseudotyped virus neutralization assay system. The dynamics of IgM and IgG antibodies and neutralizing antibodies were analyzed with exposure time or symptoms onset. Results Asymptomatics were classified into four subgroups based on NAT and serological tests. In particular, only 19% had positive NAT results while approximately 81% detected positive IgM/IgG responses. Comparative SARS-CoV-2 proteome microarray further demonstrated that there was a significantly difference of antibody dynamics responding to S1 or N proteins among three populations, although IgM and IgG profiles could not be used to differentiate them. S1 specific IgM responses were elicited in asymptomatic individuals as early to the seventh day after exposure and peaked on days from 17d to 25d, which might be used as an early diagnostic biomarker and give an additional 36.5% seropositivity. Mild patients produced stronger both S1 specific IgM and neutralizing antibody responses than asymptomatic individuals. Most importantly, S1 specific IgM/IgG responses and the titers of neutralizing antibody in asymptomatic individuals gradually vanished in two months. Conclusions and relevance Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health and immunization strategies.

scholarly journals BNT162b2 boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19

2021 ◽  
Author(s):  
Georg MN Behrens ◽  
Joana Barros-Martins ◽  
Anne Cossmann ◽  
Gema Morillas Ramos ◽  
Metodi V Stankov ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Large Scale ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immune Protection ◽  
Cell Immunity ◽  
The Impact ◽  
As Effects

Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity, and large scale second booster vaccination is ongoing. However, data comparing declining immunity after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. We longitudinally monitored immunity in ChAd/ChAd (n=41) and ChAd/BNT (n=88) vaccinated individuals and assessed the impact of a second booster with BNT in both groups. The second booster greatly augmented waning anti-spike IgG but only moderately increased spike-specific CD4+ and CD8+ T cells in both groups to cell frequencies already present after the boost. More importantly, the second booster efficiently restored neutralizing antibody responses against Alpha, Beta, Gamma, and Delta, but neutralizing activity against B.1.1.529 (Omicron) stayed severely impaired. Our data suggest that inferior SARS-CoV-2 specific immune responses after homologous ChAd/ChAd vaccination can be cured by a heterologous BNT vaccination. However, prior heterologous ChAd/BNT vaccination provides no additional benefit for spike-specific T cell immunity or neutralizing Omicron after the second boost.

scholarly journals Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stefania Dispinseri ◽  
Massimiliano Secchi ◽  
Maria Franca Pirillo ◽  
Monica Tolazzi ◽  
Martina Borghi ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Fatal Outcome ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Critical Conditions ◽  
Specific Response ◽  
Increased Risk ◽  
Neutralizing Capacity ◽  
Antibody Titers ◽  
Flu Virus

AbstractUnderstanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5–8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization.

scholarly journals The Antigenicity of Epidemic SARS-CoV-2 Variants in the United Kingdom

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiajing Wu ◽  
Li Zhang ◽  
Yue Zhang ◽  
Haixin Wang ◽  
Ruxia Ding ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Virus Vaccine ◽  
Immune Escape ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Antibody Responses ◽  
Neutralization Activity ◽  
The United Kingdom ◽  
Different Types ◽  
The Uk

To determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic SARS-CoV-2 variants in the UK, including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VOC-202012/01(B.1.1.7) and D614G+69-70del+N439K, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five SARS-CoV-2 variants and 12 single deconvolution mutants based on the variants. In this study, 18 monoclonal antibodies, 10 sera from convalescent COVID-19 patients, 10 inactivated-virus vaccine-elicited sera, 14 mRNA vaccine-elicited sera, nine RBD-immunized mouse sera, four RBD-immunized horse sera, and four spike-encoding DNA-immunized guinea pig sera were tested and analyzed. The N501Y, N439K, and S477N mutations caused immune escape from nine of 18 mAbs. However, the convalescent sera, inactivated virus vaccine-elicited sera, mRNA vaccine-elicited sera, spike DNA-elicited sera, and recombinant RBD protein-elicited sera could still neutralize these variants (within three-fold changes compared to the reference D614G variant). The neutralizing antibody responses to different types of vaccines were different, whereby the response to inactivated-virus vaccine was similar to the convalescent sera.

scholarly journals Neutralization of the emerging SARS-CoV-2 variant Lambda by antibodies elicited by inactivated virus and mRNA vaccines

2021 ◽  
Author(s):  
Mónica Acevedo ◽  
Luis Alonso-Palomares ◽  
Marco Montes de Oca ◽  
Andrés Bustamante ◽  
Aldo Gaggero ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Neutralizing Antibody ◽  
Neutralization Capacity ◽  
Antigenic Sites ◽  
Antibody Titers ◽  
Different Levels

Abstract Here, we used pseudotyped viruses to characterize the neutralization capacity of antibodies elicited by the CoronaVac and BNT162b2 vaccines against the emerging variant of interest Lambda. We observed that BNT162b2 elicits higher neutralizing antibody titers than CoronaVac, ranging from 5.8-fold for the ancestral spike to 9.4-fold for the Lambda variant. Neutralization against D614G, Alpha, Gamma, and Lambda variants was reduced between 1.78 to 3.05-fold for CoronaVac and 1.10 to 1.87-fold for BNT162b2. Structural analyses of the Lambda spike show significant changes in antigenic sites including the 246–252 deletion in an antigenic supersite at the NTD loop and, L452Q/F490S within the RBD that may account for immune escape. Our analysis of pseudotyped viruses also suggests increased infectivity driven by the Lambda spike. Together, our data indicate that inactivated virus and mRNA vaccines elicit different levels of neutralizing antibodies with different potency to neutralize SARS-CoV-2 variants, including the emergent variant Lambda.

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