scholarly journals Children develop strong and sustained cross-reactive immune responses against Spike protein following SARS-CoV-2 infection, with enhanced recognition of variants of concern

2021 ◽  
Author(s):  
Alexander C. Dowell ◽  
Megan S. Butler ◽  
Elizabeth Jinks ◽  
Gokhan Tut ◽  
Tara Lancaster ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Humoral Response ◽  
Cellular Responses ◽  
Paediatric Population ◽  
Spike Protein ◽  
High Antibody ◽  
Antibody Titres ◽  
Clinical Protection ◽  
Th1 Cytokine

AbstractSARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody profiles in children were strong, with high titres against Spike protein and receptor binding domain (RBD). SARS-CoV-2 seroconversion in children strongly boosted antibody responses against seasonal beta-coronaviruses, partly through cross-recognition of the S2 domain, indicating a broad humoral response that was not seen in adults. T cell responses against Spike were also >2-fold higher in children compared to adults and displayed a strong Th1 cytokine profile. SARS-CoV-2 Spike-reactive cellular responses were present in more than half the seronegative children, indicating pre-existing cross-reactive responses or prior sensitization against SARS-CoV-2. Importantly, all children retained high antibody titres and cellular responses for more than 6 months after infection whilst relative antibody waning was seen in adults. Significantly Children at this timepoint also had high antibody titres to B1.1.7, B1.351 and P1 variants. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection, with focussed specificity against Spike protein. These observations demonstrate several novel features of SARS-CoV-2-specific immune responses in children and may provide insights into relative clinical protection in this group. Such information on the profile of natural infection will help to guide the introduction of vaccination regimens into the paediatric population.

scholarly journals Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection

2021 ◽  
Author(s):  
Alexander C. Dowell ◽  
Megan S. Butler ◽  
Elizabeth Jinks ◽  
Gokhan Tut ◽  
Tara Lancaster ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Spike Protein ◽  
Cell Responses ◽  
Clinical Protection ◽  
Pediatric Vaccination ◽  
Insight Into

AbstractSARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3–11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

scholarly journals Differential Immunogenicity of BNT162b2 or ChAdOx1 Vaccines After Extended-Interval Homologous Dual Vaccination in Older People

2021 ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract BackgroundSeveral SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8-12 week ‘extended interval’.ObjectivesWe undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n=54) or ChAdOx1 (n=77) adenovirus vaccine. Blood samples were taken 2-3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-g ELISpot. ResultsAntibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892-8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5- 2543) in the 74 patients after the ChAdOx1 vaccine (p=<0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p=0.022).ConclusionDual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.7-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals Two doses of the SARS-CoV-2 BNT162b2 vaccine enhances antibody responses to variants in individuals with prior SARS-CoV-2 infection

2021 ◽  
pp. eabj0847
Author(s):  
Richard A Urbanowicz ◽  
Theocharis Tsoleridis ◽  
Hannah J Jackson ◽  
Lola Cusin ◽  
Joshua D Duncan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Serum Samples ◽  
Igg Antibody ◽  
Enzyme Immunoassays ◽  
Antigenic Exposure ◽  
The Impact ◽  
Prior Infection

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of healthcare workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BTN162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351 and P.1 variants with increasing antigenic exposure, either through vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein-specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

scholarly journals Controlled Infection Immunization Using Delayed Death Drug Treatment Elicits Protective Immune Responses to Blood-Stage Malaria Parasites

2018 ◽  
Vol 87 (1) ◽  
Author(s):  
Leanne M. Low ◽  
Aloysious Ssemaganda ◽  
Xue Q. Liu ◽  
Mei-Fong Ho ◽  
Victoria Ozberk ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Natural Immunity ◽  
Content Type ◽  
Human Volunteers ◽  
Pilot Clinical Study ◽  
Th1 Cytokine ◽  
Delayed Death ◽  
Extended Exposure ◽  
Homologous Challenge

ABSTRACTNaturally acquired immunity to malaria is robust and protective against all strains of the same species ofPlasmodium. This develops as a result of repeated natural infection, taking several years to develop. Evidence suggests that apoptosis of immune lymphocytes due to uncontrolled parasite growth contributes to the slow acquisition of immunity. To hasten and augment the development of natural immunity, we studied controlled infection immunization (CII) using low-dose exposure to different parasite species (Plasmodium chabaudi,P. yoelii, orP. falciparum) in two rodent systems (BALB/c and C57BL/6 mice) and in human volunteers, with drug therapy commencing at the time of initiation of infection. CIIs with infected erythrocytes and in conjunction with doxycycline or azithromycin, which are delayed death drugs targeting the parasite’s apicoplast, allowed extended exposure to parasites at low levels. In turn, this induced strong protection against homologous challenge in all immunized mice. We show thatP. chabaudi/P. yoeliiinfection initiated at the commencement of doxycycline therapy leads to cellular or antibody-mediated protective immune responses in mice, with a broad Th1 cytokine response providing the best correlate of protection against homologous and heterologous species ofPlasmodium.P. falciparumCII with doxycycline was additionally tested in a pilot clinical study (n= 4) and was found to be well tolerated and immunogenic, with immunological studies primarily detecting increased cell-associated immune responses. Furthermore, we report that a single dose of the longer-acting drug, azithromycin, given to mice (n= 5) as a single subcutaneous treatment at the initiation of infection controlledP. yoeliiinfection and protected all mice against subsequent challenge.

A MATHEMATICAL MODEL TO ASSESS THE IMMUNE RESPONSE AGAINSTTRYPANOSOMA CRUZIINFECTION

2015 ◽  
Vol 23 (01) ◽  
pp. 131-163 ◽  
Author(s):  
HYUN MO YANG
Keyword(s):  
Mathematical Model ◽  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Cellular Responses ◽  
Cellular Immune Responses ◽  
Trivial Equilibrium ◽  
Cellular Immune ◽  
Cruzi Infection

A mathematical model is developed to assess humoral and cellular immune responses against Trypanosoma cruzi infection. Analysis of the model shows a unique non-trivial equilibrium, which is locally asymptotically stable, except in the case of a strong cellular response. When the proliferation of the activated CD8 T cells is increased, this equilibrium becomes unstable and a limit cycle appears. However, this behavior can be avoided by increasing the action of the humoral response. Therefore, unbalanced humoral and cellular responses can be responsible for long asymptomatic period, and the control of Trypanosoma cruzi infection is a consequence of well coordinated action of both humoral and cellular responses.

Immune responses during the acute stages of infection with the intestinal trematode Echinostoma caproni

Parasitology ◽  
2000 ◽  
Vol 120 (6) ◽  
pp. 565-571 ◽  
Author(s):  
L. R. BRUNET ◽  
S. JOSEPH ◽  
D. W. DUNNE ◽  
B. FRIED
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Humoral Response ◽  
Spleen Cells ◽  
Echinostoma Caproni ◽  
Th2 Cytokine ◽  
Mesenteric Lymph ◽  
Cytokine Pattern ◽  
Th1 Cytokine ◽  
Ifn Γ

This study investigated the nature of the immune response of C57BL/6 mice infected with the trematode Echinostoma caproni. To determine the preferential development of either a Th1 or Th2 cytokine pattern during early stages of infection, cytokine production by spleen and mesenteric lymph node (MLN) cells during the first 3 weeks of infection was followed. Whereas spleen cells failed to respond to antigen stimulation, MLN cells produced IFN-γ and to a lesser extent IL-4. IL-5 levels were elevated throughout the period studied. The humoral response was consistent with a Th1 cytokine pattern as antigen-specific IgG2a antibodies were preferentially developed. We investigated whether IFN-γ is critical for establishment of E. caproni infection. Worm burden in infected mice treated with a single injection of anti-IFN-γ mAb was significantly reduced compared to that of animals treated with a control antibody.

scholarly journals Increasing a Robust Antigen-Specific Cytotoxic T Lymphocyte Response by FMDV DNA Vaccination with IL-9 Expressing Construct

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Qiang Zou ◽  
Bing Wu ◽  
Xiaodan He ◽  
Yizhi Zhang ◽  
Youmin Kang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cytotoxic T Lymphocyte ◽  
Humoral Response ◽  
Cellular Responses ◽  
Dna Vaccination ◽  
Specific Cell ◽  
Lymphocyte Response ◽  
Molecular Adjuvant ◽  
Cytotoxic T Lymphocyte Response

Various chemokines and cytokines as adjuvants can be used to improve efficacy of DNA vaccination. In this study, we sought to investigate if a DNA construct expressing IL-9 (designed as proV-IL9) as a molecular adjuvant enhance antigen specific immune responses elicited by the pcD-VP1 DNA vaccination. Mice immunized with pcD-VP1 combined with proV-IL9 developed a strong humoral response. In addition, the coinoculation induced significant higher level of antigen-specific cell proliferation and cytotoxic response. This agreed well with higher expression level of IFN-γand perforin in CD8+T cells, but not with IL-17 in these T cells. The results indicate that IL-9 induces the development of IFN-γ-producing CD8+T cells (Tc1), but not the IL-17-producing CD8+T cells (Tc17). Up-regulated expressions of BCL-2 and BCL-XL were exhibited in these Tc1 cells, suggesting that IL-9 may trigger antiapoptosis mechanism in these cells. Together, these results demonstrated that IL-9 used as molecular adjuvant could enhance the immunogenicity of DNA vaccination, in augmenting humoral and cellular responses and particularly promoting Tc1 activations. Thus, the IL-9 may be utilized as a potent Tc1 adjuvant for DNA vaccines.

scholarly journals Humoral Response Induced by Prime-Boost Vaccination with the ChAdOx1 nCoV-19 and mRNA BNT162b2 Vaccines in a Teriflunomide-Treated Multiple Sclerosis Patient

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1140
Author(s):  
Yves Michiels ◽  
Nadhira Houhou-Fidouh ◽  
Gilles Collin ◽  
Jérôme Berger ◽  
Evelyne Kohli
Keyword(s):  
Multiple Sclerosis ◽  
Immune Responses ◽  
Antibody Response ◽  
Viral Vector ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Protein S ◽  
Spike Protein ◽  
Vaccination Regimen ◽  
The Past

Patients with multiple sclerosis (MS) are treated with drugs that may impact immune responses to SARS-CoV-2 vaccination. Evaluation of “prime-boost” (heterologous) vaccination regimens including a first administration of a viral vector-based vaccine and a second one of an mRNA-based vaccine in such patients has not yet been completed. Here, we present the anti-spike protein S humoral response, including the neutralizing antibody response, in a 54-year-old MS patient who had been treated with teriflunomide for the past 2 years and who received a heterologous ChAdOx1 nCoV-19/ BNT162b2 vaccination regimen. The results showed a very strong anti-S IgG response and a good neutralizing antibody response. These results show that teriflunomide did not prevent the development of a satisfactory humoral response in this MS patient after vaccination with a ChAdOx1 nCoV-19/ BNT162b2 prime-boost protocol.

scholarly journals Differential immunogenicity of BNT162b2 or ChAdOx1 vaccines after extended-interval homologous dual vaccination in older people

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract Background Several SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8–12 week ‘extended interval’. Objectives We undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n = 54) or ChAdOx1 (n = 77) adenovirus vaccine. Blood samples were taken 2–3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-γ ELISpot. Results Antibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892–8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5–2543) in the 74 patients after the ChAdOx1 vaccine (p = < 0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p = 0.022). Conclusion Dual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.4-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals Serological surveillance of SARS-CoV-2: trends and humoral response in a cohort of public health workers

2020 ◽  
Author(s):  
Ross J Harris ◽  
Heather J Whitaker ◽  
Nick J Andrews ◽  
Felicity Aiano ◽  
Zahin Amin-Chowdhury ◽  
...  
Keyword(s):  
Half Life ◽  
Healthcare Workers ◽  
Health Workers ◽  
Natural Infection ◽  
Humoral Response ◽  
Spike Protein ◽  
Positive Test ◽  
Public Health Workers ◽  
Serological Surveillance ◽  
Antibody Levels

AbstractBackgroundThere is considerable debate about the rate of antibody waning after SARS-CoV-2 infection, raising questions around long-term immunity following both natural infection and vaccination. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.MethodsThe serosurveillance cohort included office and laboratory-based staff and healthcare workers in 4 sites in England, who were tested monthly for SARS-CoV-2 spike protein and nucleoprotein IgG between 23rd March and 20th August 2020. Antibody levels from 21 days after a positive test were modelled using mixed effects regression models.FindingsIn total, 2247 individuals were recruited and 2014 (90%) had 3-5 monthly antibody tests. Overall, 272 (12.1%) of individuals had at least one positive/equivocal spike protein IgG result, with the highest proportion in a hospital site (22%), 14% in London and 2.1% in a rural area. Results were similar for nucleoprotein IgG. Following a positive result, 39/587 (6.6%) tested negative for nucleoprotein IgG and 52/515 (10.1%) for spike protein IgG. Nucleoprotein IgG declined by 6.4% per week (95% CI, 5.5-7.4%; half-life, 75 [95% CI, 66-89] days) and spike protein IgG by 5.8% (95% CI, 5.1-6.6%; half-life, 83 [95% CI, 73-96] days).ConclusionsOver the study period SARS-CoV-2 seropositivity was 8-10% overall and up to 21% in clinical healthcare workers. In seropositive individuals, nucleoprotein and spike protein IgG antibodies declined with time after infection and 50% are predicted to fall below the positive test threshold after 6 months.FundingPHE

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