Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Henze, Larissa; Braun, Julian; Meyer-Arndt, Lil; Jürchott, Karsten; Schlotz, Maike; Michel, Janine; Grossegesse, Marica; Mangold, Maike; Dingeldey, Manuela; Kruse, Beate; Holenya, Pavlo; Mages, Norbert; Reimer, Ulf; Eckey, Maren; Schnatbaum, Karsten; Wenschuh, Holger; Timmermann, Bernd; Klein, Florian; Nitsche, Andreas; Giesecke‐Thiel, Claudia; Loyal, Lucie; Thiel, Andreas

doi:10.3389/fimmu.2023.1056525

Cited by 4 publications

(5 citation statements)

References 63 publications

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“…Like adults, the administration of two doses of the BNT vaccine is required to generate an optimal immune response in children. Furthermore, the dosing interval has been shown to influence the vaccine-induced humoral response (27)(28)(29)(30). In the present study, we did not observe a noticeable difference in the levels of the BNT vaccine-induced anti-RBD IgG antibody response between the SARS-CoV-2-infection-naive schoolchildren who received one dose and those who received two doses.…”

Section: Discussioncontrasting

confidence: 52%

“…In addition, the predicted median time to breakthrough infection following mRNA vaccination, including BNT, has been shown to be longer than the median time to breakthrough infections following viral vector vaccination ( 27 ). Further, unlike adenovirus-vector COVID-19 vaccines, vaccination with BNT has been shown to reactivate pre-existing, cross-reactive T-cell immunity, particularly in children ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Infection-and mRNA Vaccine-induced Humoral Immunity among Schoolchildren in Hawassa, Ethiopia

et al. 2023

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BackgroundWith the persisting low vaccination intake, particularly in children of low-and middle-income countries (LMICs), seroepidemiological studies are urgently needed to guide and tailor COVID-19 pandemic response efforts in schools and to put mitigation strategies in place for a future post-pandemic resurgence. However, there is limited data on SARS-CoV-2 infection-induced and vaccine-induced humoral immunity in schoolchildren in LMICs, including Ethiopia.MethodsAs the spike receptor binding domain (RBD) is the major target for neutralization antibodies and useful to predict the correlates of protection, we used an in-house anti-RBD IgG ELISA to assess and compare infection-induced antibody response at two-time points and BNT162b2 (BNT) vaccine-induced antibody response at a one-time point in schoolchildren in Hawassa, Ethiopia. In addition, we measured and compared the levels of binding IgA antibodies to spike RBD of SARS-CoV-2 Wild type, Delta, and Omicron variants in a small subset of unvaccinated and BNT-vaccinated schoolchildren.ResultsWhen we compare SARS-CoV-2 infection-induced seroprevalences among unvaccinated school children (7-19 years) at the two blood sampling points with a 5-month interval, we observed an over 10% increase, from 51.8% (219/419) in the first week of December 2021 (post-Delta wave) to 67.4% (60/89) by the end of May 2022 (post-Omicron wave). Additionally, we found a significant correlation (p = 0.001) between anti-RBD IgG seropositivity and a history of having COVID-19-like symptoms. Compared to the levels of SARS-CoV-2 infection-induced anti-RBD IgG antibodies before vaccination, higher levels of BNT vaccine-induced anti-RBD IgG antibodies were observed even in SARS-CoV-2 infection-naïve schoolchildren of all age groups (p = 0.0001). Importantly, one dose of the BNT vaccine was shown to be adequate to elicit a strong antibody response in schoolchildren with pre-existing anti-RBD IgG antibodies comparable to that of SARS-CoV-2 infection-naive schoolchildren receiving two doses of BNT vaccine, suggesting a single dose administration of the BNT vaccine could be considered for schoolchildren who had prior SARS-CoV-2 infection when a shortage of vaccine supply is a limiting factor to administer two doses irrespective of their serostatus. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Irrespective of schoolchildren’s vaccination status, we observed a similar pattern of significantly higher levels of IgA antibodies to Delta-RBD than to Omicron-RBD (p < 0.001) in a randomly selected subset of schoolchildren, yet comparable to Wuhan-RBD, suggesting these schoolchildren were more likely to have had SARS-CoV-2 infection with Delta variant. Additionally, we noted a broader IgA antibody reactivity to SARS-CoV-2 variants in vaccinated schoolchildren with prior SARS-CoV-2 infection, supporting the superiority of hybrid immunity.ConclusionOur serological data indicate a significant increase in SARS-CoV-2 seroprevalence in children at a post-Omicron five-month follow-up compared to a post-Delta enrolment. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Hybrid immunity would likely provide a broader humoral immunity against Wuhan strain, Delta, and Omicron variants than natural infection or vaccination alone does. However, future longitudinal cohort studies in SARS-CoV-2-naïve and COVID-19-recovered schoolchildren receiving the BNT vaccine are needed for a better understanding of the kinetics, breadth, and durability of BNT vaccine-induced multivariant-cross reactive immunity.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infection-and mRNA Vaccine-induced Humoral Immunity among Schoolchildren in Hawassa, Ethiopia

et al. 2023

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“…Remarkably, the adenovirus-based ChAdOx1 nCOV-19 (Asta-Zeneca) vaccine did not recall cross-reactive T cells . Numerous differences in vaccine composition and route of delivery could explain a difference in the recall of cross-reactive T cells.…”

Section: Unstable and Metastable Viral Surface Proteinsmentioning

confidence: 99%

“…Remarkably, the adenovirus-based ChAdOx1 nCOV-19 (Asta-Zeneca) vaccine did not recall cross-reactive T cells. 92 Numerous differences in vaccine composition and route of delivery could explain a difference in the recall of cross-reactive T cells. Nevertheless, a prominent difference is the fact that the mRNA-coded spike was conformationally stabilized by two proline substitutions in S2 but this adenovirus-coded spike was not.…”

Section: Unstable and Metastable Viral Surface Proteinsmentioning

confidence: 99%

Structural Framework for Analysis of CD4+ T-Cell Epitope Dominance in Viral Fusion Proteins

et al. 2023

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Antigen conformation shapes CD4+ T-cell specificity through mechanisms of antigen processing, and the consequences for immunity may rival those from conformational effects on antibody specificity. CD4+ T cells initiate and control immunity to pathogens and cancer and are at least partly responsible for immunopathology associated with infection, autoimmunity, and allergy. The primary trigger for CD4+ T-cell maturation is the presentation of an epitope peptide in the MHC class II antigen-presenting protein (MHCII), most commonly on an activated dendritic cell, and then the T-cell responses are recalled by subsequent presentations of the epitope peptide by the same or other antigen-presenting cells. Peptide presentation depends on the proteolytic fragmentation of the antigen in an endosomal/lysosomal compartment and concomitant loading of the fragments into the MHCII, a multistep mechanism called antigen processing and presentation. Although the role of peptide affinity for MHCII has been well studied, the role of proteolytic fragmentation has received less attention. In this Perspective, we will briefly summarize evidence that antigen resistance to unfolding and proteolytic fragmentation shapes the specificity of the CD4+ T-cell response to selected viral envelope proteins, identify several remarkable examples in which the immunodominant CD4+ epitopes most likely depend on the interaction of processing machinery with antigen conformation, and outline how knowledge of antigen conformation can inform future efforts to design vaccines.

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“…The method presented here enabled us to investigate the complete immune response by mapping all coronavirus antigens in parallel and to analyze the potential epitopes at the level of amino acid variations, for example, the naïve sequence and accepted variations. This is necessary because, due to the similarity of the antigens, it was expected and confirmed that healthy persons can have an established cross-reactive immune response to SARS-CoV-2 at B- and T-cell levels [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], although this is not always activated by vaccination [ 33 ]. This immune response is not restricted to the virus coat proteins but the T-cell response is also found for the NSP12 [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Detection of Antibodies against Endemic and SARS-CoV-2 Coronaviruses with Short Peptide Epitopes

Szardenings,

Delaroque,

Kern

et al. 2023

Vaccines

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(1) Background: Coronavirus proteins are quite conserved amongst endemic strains (eCoV) and SARS-CoV-2. We aimed to evaluate whether peptide epitopes might serve as useful diagnostic biomarkers to stratify previous infections and COVID-19. (2) Methods: Peptide epitopes were identified at an amino acid resolution that applied a novel statistical approach to generate data sets of potential antibody binding peptides. (3) Results: Data sets from more than 120 COVID-19 or eCoV-infected patients, as well as vaccinated persons, have been used to generate data sets that have been used to search in silico for potential epitopes in proteins of SARS-CoV-2 and eCoV. Peptide epitopes were validated with >300 serum samples in synthetic peptide micro arrays and epitopes specific for different viruses, in addition to the identified cross reactive epitopes. (4) Conclusions: Most patients develop antibodies against non-structural proteins, which are useful general markers for recent infections. However, there are differences in the epitope patterns of COVID-19, and eCoV, and the S-protein vaccine, which can only be explained by a high degree of cross-reactivity between the viruses, a pre-existing immune response against some epitopes, and even an alternate processing of the vaccine proteins.

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Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Cited by 4 publications

References 63 publications

SARS-CoV-2 Infection-and mRNA Vaccine-induced Humoral Immunity among Schoolchildren in Hawassa, Ethiopia

SARS-CoV-2 Infection-and mRNA Vaccine-induced Humoral Immunity among Schoolchildren in Hawassa, Ethiopia

Structural Framework for Analysis of CD4+ T-Cell Epitope Dominance in Viral Fusion Proteins

Detection of Antibodies against Endemic and SARS-CoV-2 Coronaviruses with Short Peptide Epitopes

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