Delta infection following vaccination elicits potent neutralizing immunity against the SARS-CoV-2 Omicron

Abstract Since the initial detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) in November 2021 in South Africa, it has caused a rapid increase in infections globally. The Omicron variant encodes 37 amino acid substitutions in its spike protein, and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness. We assessed serum neutralizing activity in sera from Delta infection following vaccination of CoronaVac or ZF2001 and Delta infection only against SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, Delta, and Omicron. We found that sera from Delta infection only could neutralize WA1 and Delta pseudoviruses but nearly completely lost capacity to neutralize Beta and Omicron pseudoviruses. However, Delta infection following vaccination resulted in a significant increase of serum neutralizing activity against WA1, Beta, and Omicron. This study demonstrates that breakthrough infection of Delta in previously vaccinated individuals substantially induced high potency humoral immune response against the Omicron variant and other emerged variants.

Download Full-text

Crucial Mutations of Spike Protein on SARS-CoV-2 Evolved to Variant Strains Escaping Neutralization of Convalescent Plasmas and RBD-Specific Monoclonal Antibodies

Frontiers in Immunology ◽

10.3389/fimmu.2021.693775 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chengchao Ding ◽

Jun He ◽

Xiangyu Zhang ◽

Chengcheng Jiang ◽

Yong Sun ◽

...

Keyword(s):

Immune Response ◽

Monoclonal Antibodies ◽

Humoral Immune Response ◽

Immune Escape ◽

Spike Protein ◽

Single Amino Acid ◽

Humoral Immune ◽

Cross Neutralization ◽

Altered Sensitivity ◽

Single Amino Acid Mutation

Small number of SARS-CoV-2 epidemic lineages did not efficiently exhibit a neutralization profile, while single amino acid mutation in the spike protein has not been confirmed in altering viral antigenicity resulting in immune escape. To identify crucial mutations in spike protein that escape humoral immune response, we evaluated the cross-neutralization of convalescent plasmas and RBD-specific monoclonal antibodies (mAbs) against various spike protein-based pseudoviruses. Three of 24 SARS-CoV-2 pseudoviruses containing different mutations in spike protein, including D614G, A475V, and E484Q, consistently showed an altered sensitivity to neutralization by convalescent plasmas. A475V and E484Q mutants are highly resistant to neutralization by mAb B38 and 2-4, suggesting that some crucial mutations in spike protein might evolve SARS-CoV-2 variants capable of escaping humoral immune response.

Download Full-text

Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines

Cell Research ◽

10.1038/s41422-021-00514-9 ◽

2021 ◽

Author(s):

Yunlong Cao ◽

Ayijiang Yisimayi ◽

Yali Bai ◽

Weijin Huang ◽

Xiaofeng Li ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Mononuclear Cells ◽

Immune Escape ◽

Natural Infection ◽

Peripheral Blood Mononuclear ◽

Neutralizing Activity ◽

Humoral Immune ◽

Complementarity Determining Regions

AbstractSARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242–244 deletion (242–244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242–244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.

Download Full-text

SARS-CoV-2 RNA and antibodies in tear fluid

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2021-000733 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000733

Author(s):

Astrid Muyldermans ◽

Maria Bjerke ◽

Thomas Demuyser ◽

Deborah De Geyter ◽

Ingrid Wybo ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Spike Protein ◽

Tear Fluid ◽

Local Response ◽

Schirmer Test ◽

Humoral Immune ◽

Non Invasive ◽

Reverse Transcription Pcr ◽

Ocular Symptoms

Background/aimsSARS-CoV-2 is highly contagious. More evidence concerning extrapulmonary transmission routes such as the eyes is urgently needed. Although the humoral immune response is important in the viral containment, the local response in tears has not yet been studied. The aim of our study was twofold: to assess the prevalence of both SARS-CoV-2 RNA and antibodies in tear fluid.MethodsIn a first series, nasopharyngeal sampling and tear sampling by Schirmer test strips were performed in 26 acutely ill patients with COVID-19 to assess the presence of SARS-CoV-2 RNA by reverse transcription PCR. In a second series, IgG and IgA responses to SARS-CoV-2 spike protein in serum and tear fluid of convalescent individuals (n=22) were compared with control individuals (n=15) by ELISA.ResultsSARS-CoV-2 RNA was detected in tears of 7/26 (26.9%) patients with COVID-19. None of them had ocular symptoms. Convalescent individuals displayed a significant higher ratio of IgG (p<0.0001) and IgA (p=0.0068) in tears compared with control individuals. A sensitivity of 77.3% and specificity of 93.3% was observed for IgG, and 59.1% and 100% for IgA.ConclusionsOur results demonstrate the presence of SARS-CoV-2 RNA and a local IgG and IgA immune response in tear fluid. These data confirm the possibility of SARS-CoV-2 transmission through tear fluid and the importance of the eye as a first defence against SARS-CoV-2, indicating the potential of tears as a non-invasive surrogate for serum in monitoring the host immune response.

Download Full-text

Immunological imprinting of the antibody response in COVID-19 patients

Nature Communications ◽

10.1038/s41467-021-23977-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Teresa Aydillo ◽

Alexander Rombauts ◽

Daniel Stadlbauer ◽

Sadaf Aslam ◽

Gabriela Abelenda-Alonso ◽

...

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Antibody Response ◽

Humoral Immune Response ◽

Nucleocapsid Protein ◽

Spike Protein ◽

Ongoing Research ◽

Variable Regions ◽

Humoral Immune ◽

Human Coronaviruses

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.

Download Full-text

The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study

10.1101/2020.12.23.424283 ◽

2020 ◽

Author(s):

Filip Fratev

Keyword(s):

South Africa ◽

Immune Response ◽

Free Energy ◽

Molecular Level ◽

Spike Protein ◽

Free Energy Perturbation ◽

Receptor Binding Domain ◽

Human Immune Response ◽

Human Immune ◽

Energy Perturbation

AbstractThe N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased; about over 100 times. The K417N mutation had much more pronounced effect and in a combination with N501Y fully abolished the antibody effect. This may explain the observed in UK and South Africa more spread of the virus but also raise an important question about the possible human immune response and the success of already available vaccines.

Download Full-text

The Porcine Humoral Immune Response against Pseudorabies Virus Specifically Targets Attachment Sites on Glycoprotein gC

Journal of Virology ◽

10.1128/jvi.74.4.1752-1760.2000 ◽

2000 ◽

Vol 74 (4) ◽

pp. 1752-1760 ◽

Cited By ~ 24

Author(s):

Bertram T. Ober ◽

Berthold Teufel ◽

Karl-Heinz Wiesmüller ◽

Günther Jung ◽

Eberhard Pfaff ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Pseudorabies Virus ◽

Host Protein ◽

Target Cells ◽

Heparin Binding ◽

Viral Attachment ◽

Neutralizing Activity ◽

Humoral Immune

ABSTRACT High titers of virus-neutralizing antibodies directed against glycoprotein gC of Pseudorabies virus (PRV) (Suid herpesvirus 1) are generally observed in the serum of immunized pigs. A known function of the glycoprotein gC is to mediate attachment of PRV to target cells through distinct viral heparin-binding domains (HBDs). Therefore, it was suggested that the virus-neutralizing activity of anti-PRV sera is directed against HBDs on gC. To address this issue, sera with high virus-neutralizing activity against gC were used to characterize the anti-gC response. Epitope mapping demonstrated that amino acids of HBDs are part of an antigenic antibody binding domain which is located in the N-terminal part of gC. Binding of antibodies to this antigenic domain of gC was further shown to interfere with the viral attachment. Therefore, these results show that the viral HBDs are accessible targets for the humoral anti-PRV response even after tolerance induction against self-proteins, which utilize similar HBDs to promote host protein-protein interactions. The findings indicate that the host's immune system can specifically block the attachment function of PRV gC. Since HBDs promote the attachment of a number of herpesviruses, the design of future antiherpesvirus vaccines should aim to induce a humoral immune response that prevents HBD-mediated viral attachment.

Download Full-text

The duration and specificity of the humoral immune response to SARS-CoV-2

Likarska sprava ◽

10.31640/jvd.3-4.2021(2) ◽

2021 ◽

pp. 7-12

Author(s):

E. I. Dubrovskyi ◽

B. V. Dons’koi

Keyword(s):

Immune Response ◽

Quality Control ◽

Humoral Response ◽

Threshold Value ◽

Spike Protein ◽

Obstetrics And Gynecology ◽

Study Group ◽

Specific Antibodies ◽

Humoral Immune ◽

Pcr Test

Background. Our assumption that immunity after COVID-19 will persist has been fully confirmed in the researches already conducted. Our work is a continuation of research that demonstrates the results obtained 12 months of determining the humoral response in patients after COVID-19. Materials and methods. The research involved 42 individuals. All subjects had a positive PCR test for COVID-19. At certain intervals, from 40 to 240 days, individuals in the group were tested for IgG SARS-CoV-2. The last step was to check the level of IgG to the COVID-19 nucleocapsid and spike protein in the research group for 360 days from the onset of the disease. A private certified laboratory in Kyiv, the “DNA Laboratory”, was involved. Patients were tested for antibodies to COVID-19 by ELISA using serology COVID-19 test systems VitroTest (Ukraine). The immunological laboratory of the Institute of Pediatrics, Obstetrics and Gynecology was used in parallel for interlaboratory quality control. The results of the research coincided. Results. The level of class G immunoglobulins to nucleocapsid in the subjects has gradually decreased over 8 months. It is noteworthy that in the period from 40 to 150 days in all 42 patients (100 %) antibodies did not disappear. Decreasing of antibodies occurred between 150 and 240 days. However, the data obtained for 360 days significantly changed the picture. In a certain part of the subjects, who had low or even negative levels of antibodies for 8 months, as of 12 months, the level of immunoglobulin (Ig) class G again rose above the threshold value. Thus, we see that from the group of 42 people 92.8 % have positive antibodies to the nucleocapsid, and 7.2 %. Conclusions. The data obtained illustrate that in the study group within 12 months after SARS-CoV-2, the vast majority of individuals remain with specific antibodies to the nucleocapsid and spike-protein.

Download Full-text

Development of a Unique Rapid Test to Detect Anti-bodies Directed Against an Extended RBD of SARS-CoV-2 Spike Protein

CHIMIA International Journal for Chemistry ◽

10.2533/chimia.2021.446 ◽

2021 ◽

Vol 75 (5) ◽

pp. 446-452

Author(s):

Larissa Brosi ◽

Eric Kübler ◽

Anna Weston ◽

Patrick Romann ◽

Sherin Panikulam ◽

...

Keyword(s):

Immune Response ◽

Receptor Binding ◽

Recombinant Expression ◽

Rapid Test ◽

High Sensitivity ◽

Spike Protein ◽

Receptor Binding Domain ◽

Serological Testing ◽

Humoral Immune ◽

Previous Infection

Serological testing for antibodies directed against SARS-CoV-2 in patients may serve as a diagnostic tool to verify a previous infection and as surrogate for an elicited humoral immune response, ideally conferring immunity after infection or vaccination. Here, we present the recombinant expression of an extended receptor binding domain (RBD) of the SARS-CoV-2 Spike protein used as capture antigen in a unique rapid immunoassay to detect the presence of RBD binding antibodies with high sensitivity and specificity. As currently available vaccines focus on the Spike RBD as target, the developed test can also be used to monitor a successful immune response after vaccination with an RBD based vaccine.

Download Full-text

A comparative analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda

10.1101/2021.11.04.467302 ◽

2021 ◽

Author(s):

S Jake Gonzales ◽

Kathleen N Clarke ◽

Gayani Batugedara ◽

Ashley E Braddom ◽

Rolando Garza ◽

...

Keyword(s):

Immune Response ◽

Plasmodium Falciparum ◽

B Cells ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Antibody Responses ◽

Amino Acid Substitutions ◽

Humoral Immune ◽

Merozoite Surface Protein 1 ◽

Specific Igg

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against P. falciparum develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, merozoite surface protein 1 (MSP1), in individuals from a region in Uganda with high P. falciparum transmission. Our results showed that MSP1-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ MSP1-specific classical MBCs. In contrast, anti-MSP1 plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against MSP1 and whole merozoites, with broadening of the response against non-3D7 strains in adults. The antibodies encoded by MSP1-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable MSP1 protein. Proteomics analysis of MSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to MSP1-specific MBCs, anti-MSP1 IgGs had relatively high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the MSP1-specific humoral immune response with cumulative P. falciparum exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of MSP1 variants by the plasma IgG repertoire.

Download Full-text

Sensitivity of two SARS-CoV-2 variants with spike protein mutations to neutralising antibodies

Virus Genes ◽

10.1007/s11262-021-01871-8 ◽

2021 ◽

Author(s):

Katharina Müller ◽

Philipp Girl ◽

Andreas Giebl ◽

Stefanie Gruetzner ◽

Markus Antwerpen ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Point Of View ◽

Spike Protein ◽

Wild Type ◽

Serum Samples ◽

Antibody Treatment ◽

Neutralising Antibodies ◽

Humoral Immune ◽

Protein Mutations

AbstractSARS-CoV-2 infections elicit a humoral immune response capable of neutralising the virus. However, multiple variants have emerged with mutations in the spike protein amongst others, the key target of neutralising antibodies. We evaluated the neutralising efficacy of 89 serum samples from patients, infected with SARS-CoV-2 in the beginning of 2020, against two virus variants isolated from acutely infected patients and harbouring spike protein mutations. One isolate was assigned to lineage B.1.351 (MUC-IMB-B.1.351) whilst the other (MUC-484) was isolated from an immunocompromised patient, sharing some but not all mutations with B.1.351 and representing a transitional variant. Both variants showed a significant reduction in neutralisation sensitivity compared to wild-type SARS-CoV-2 with MUC-IMB-B.1.351 being almost completely resistant to neutralisation. The observed reduction in neutralising activity of wild-type-specific antibodies against both variants suggests that individual mutations in the spike protein are sufficient to confer a potent escape from the humoral immune response. In addition, the effect of escape mutations seems to accumulate, so that more heavily mutated variants show a greater loss of sensitivity to neutralisation up to complete insensitivity as observed for MUC-IMB-B.1.351. From a clinical point of view, this might affect the efficacy of (monoclonal) antibody treatment of patients with prolonged infections as well as patients infected with variants other than the donor. At the same, this could also negatively influence the efficacy of current vaccines (as they are based on wild-type spike protein) emphasising the need to thoroughly surveil the emergence and distribution of variants and adapt vaccines and therapeutics accordingly.

Download Full-text