scholarly journals mRNA COVID-19 vaccines induce enhanced antibody and cellular responses compared to ChAdOx1 or natural infection in children

2021 ◽  
Author(s):  
Alexander Dowell ◽  
Annable Powell ◽  
Chris Davis ◽  
Brian Willett ◽  
Rachel Bruton ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Infection ◽  
Cellular Responses ◽  
Effector Memory ◽  
Live Virus ◽  
Cell Responses ◽  
Antibody Titres ◽  
Antibody Levels ◽  
Optimal Protection

Abstract We present a comprehensive analysis of antibody and cellular responses in children aged 12-16 years who received COVID-19 vaccination with ChAdOx1 (n=6) or mRNA vaccine (mRNA-1273 or BNT162b2, n=9) using a 12-week extended-interval schedule. mRNA vaccination of seropositive children induces high antibody levels, with one dose, but a second dose is required in infection-naïve children. Following a second ChAdOx1 dose, antibody titres were higher than natural infection, but lower than mRNA vaccination. Vaccination induced live virus neutralising antibodies against Alpha, Beta and Delta variants, however, a second dose is required in infection-naïve children. We found higher T-cell responses following mRNA vaccination than ChAdOx1. Phenotyping of responses showed predominantly early effector-memory CD4 T cell populations, with a type-1 cytotoxic cytokine signature, with IL-10. These data demonstrate mRNA vaccination induces a co-ordinated superior antibody and robust cellular responses in children. Seronegative children require a prime-boost regime for optimal protection.

scholarly journals Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1490
Author(s):  
Victoria Matyushenko ◽  
Irina Isakova-Sivak ◽  
Igor Kudryavtsev ◽  
Arina Goshina ◽  
Anna Chistyakova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Natural Infection ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

scholarly journals Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens

2009 ◽  
Vol 83 (11) ◽  
pp. 5881-5889 ◽  
Author(s):  
Petra Mooij ◽  
Sunita S. Balla-Jhagjhoorsingh ◽  
Niels Beenhakker ◽  
Patricia van Haaften ◽  
Ilona Baak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Interleukin 2 ◽  
T Cell Responses ◽  
Effector Memory ◽  
Data Set ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-γ) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4+ and CD8+ T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-γ, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-γ T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.

scholarly journals Antibody and T cell responses to Sinopharm/BBIBP-CorV in naive and previously infected individuals in Sri Lanka

2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Inoka Sepali Aberathna ◽  
Pradeep Dharshana Pushpakumara ◽  
Achala Kamaladasa ◽  
Dinuka Guruge ◽  
...  
Keyword(s):  
T Cell ◽  
Sri Lanka ◽  
Ex Vivo ◽  
Natural Infection ◽  
T Cell Responses ◽  
Antibody Responses ◽  
Receptor Blocking ◽  
Cell Responses ◽  
Antibody Titres ◽  
Blocking Antibodies

Background: As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. Methods: SARS-CoV-2-specific antibodies were measured in 282 individuals who were seronegative at baseline, and ACE2 receptor blocking antibodies, antibodies to the receptor binding domain (RBD) of the wild type (WT), B.1.1.7, B.1.351 and B.1.617.2, ex vivo and cultured IFNγ ELISpot assays, intracellular cytokine secretion assays and B cell ELISpot assays were carried out in a sub cohort of the vaccinees at 4 weeks and at 6 weeks (2 weeks after the second dose). Results: 95% of the vaccinees seroconverted, although the seroconversion rates were significantly lower (p<0.001) in individuals >60 years (93.3%) compared to those who were 20 to 39 years (98.9%). 81.25% had ACE2 receptor blocking antibodies at 6 weeks, and there was no difference in these antibody titres in vaccine sera compared to convalescent sera (p=0.44). Vaccinees had significantly less (p<0.0001) antibodies to the RBD of WT and B.1.1.7, although there was no difference in antibodies to the RBD of B.1.351 and B.1.617.2 compared to convalescent sera. 27.7% of 46.4% of vaccinees had ex vivo IFNγ and cultured ELISpot responses respectively, and IFNγ and CD107a responses were detected by flow cytometry. Conclusions: Sinopharm/BBIBP-CorV appeared to induce high seroconversion rates and induce a similar level of antibody responses against ACE2 receptor, B.1.617.2 and B.1.351 as seen following natural infection.

scholarly journals SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings From The COV-AD Study

2022 ◽  
Author(s):  
Adrian M Shields ◽  
Sian E. Faustini ◽  
Harriet J. Hill ◽  
Saly Al-Taei ◽  
Chloe Tanner ◽  
...  
Keyword(s):  
Recurrent Infection ◽  
Cellular Responses ◽  
Antibody Deficiency ◽  
Breakthrough Infection ◽  
Live Virus ◽  
Post Vaccination ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Interferon Gamma Release Assays ◽  
Antibody Levels

Abstract Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives COVID in patients with antibody deficiency (COV-AD) is a multi-site United Kingdom study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods Individuals on immunoglobulin replacement therapy or with an IgG less than 4g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results 5.6% (n=320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n=168) compared with 100% of healthy controls (n=205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs 48.0%, p=0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs 2.39, p=0.0003). T cell responses post vaccination were demonstrable in 46.2% of participants, were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

scholarly journals A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Lind ◽  
Ilaria Marzinotto ◽  
Cristina Brigatti ◽  
Anita Ramelius ◽  
Lorenzo Piemonti ◽  
...  
Keyword(s):  
Antibody Response ◽  
Antigenic Determinant ◽  
Etiological Agent ◽  
Healthy Controls ◽  
Antibody Affinity ◽  
Antibody Titres ◽  
Antibody Levels ◽  
And Control ◽  
Radiobinding Assay

AbstractAn increased incidence of narcolepsy type 1 (NT1) was observed in Scandinavia following the 2009–2010 influenza Pandemrix vaccination. The association between NT1 and HLA-DQB1*06:02:01 supported the view of the vaccine as an etiological agent. A/H1N1 hemagglutinin (HA) is the main antigenic determinant of the host neutralization antibody response. Using two different immunoassays, the Luciferase Immunoprecipitation System (LIPS) and Radiobinding Assay (RBA), we investigated HA antibody levels and affinity in an exploratory and in a confirmatory cohort of Swedish NT1 patients and healthy controls vaccinated with Pandemrix. HA antibodies were increased in NT1 patients compared to controls in the exploratory (LIPS p = 0.0295, RBA p = 0.0369) but not in the confirmatory cohort (LIPS p = 0.55, RBA p = 0.625). HA antibody affinity, assessed by competition with Pandemrix vaccine, was comparable between patients and controls (LIPS: 48 vs. 39 ng/ml, p = 0.81; RBA: 472 vs. 491 ng/ml, p = 0.65). The LIPS assay also detected higher HA antibody titres as associated with HLA-DQB1*06:02:01 (p = 0.02). Our study shows that following Pandemrix vaccination, HA antibodies levels and affinity were comparable NT1 patients and controls and suggests that HA antibodies are unlikely to play a role in NT1 pathogenesis.

scholarly journals The Frequency and Immunodominance of Islet-Specific CD8+ T-cell Responses Change after Type 1 Diabetes Diagnosis and Treatment

Diabetes ◽  
2008 ◽  
Vol 57 (5) ◽  
pp. 1312-1320 ◽  
Author(s):  
E. Martinuzzi ◽  
G. Novelli ◽  
M. Scotto ◽  
P. Blancou ◽  
J.-M. Bach ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Diagnosis And Treatment ◽  
Diabetes Diagnosis ◽  
Cell Responses

scholarly journals Comprehensive Epitope Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses Directed against the Entire Expressed HIV-1 Genome Demonstrate Broadly Directed Responses, but No Correlation to Viral Load

2003 ◽  
Vol 77 (3) ◽  
pp. 2081-2092 ◽  
Author(s):  
M. M. Addo ◽  
X. G. Yu ◽  
A. Rathod ◽  
D. Cohen ◽  
R. L. Eldridge ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Protein Subunits ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Total Magnitude ◽  
Cellular Immune ◽  
Hiv 1

ABSTRACT Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/106 PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

scholarly journals Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1

2005 ◽  
Vol 86 (2) ◽  
pp. 349-354 ◽  
Author(s):  
Eva K. L. Nordström ◽  
Mattias N. E. Forsell ◽  
Christina Barnfield ◽  
Eivor Bonin ◽  
Tomas Hanke ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Dna Vaccine ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Semliki Forest Virus ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

With the human immunodeficiency virus type 1 (HIV-1) epidemic expanding at increasing speed, development of a safe and effective vaccine remains a high priority. One of the most central vaccine platforms considered is plasmid DNA. However, high doses of DNA and several immunizations are typically needed to achieve detectable T-cell responses. In this study, a Semliki Forest virus replicon DNA vaccine designed for human clinical trials, DREP.HIVA, encoding an antigen that is currently being used in human trials in the context of a conventional DNA plasmid, pTHr.HIVA, was generated. It was shown that a single immunization of DREP.HIVA stimulated HIV-1-specific T-cell responses in mice, suggesting that the poor immunogenicity of conventional DNA vaccines may be enhanced by using viral replicon-based plasmid systems. The results presented here support the evaluation of Semliki Forest virus replicon DNA vaccines in non-human primates and in clinical studies.

scholarly journals Enhanced T- and B-cell responses to simian immunodeficiency virus (SIV)agm, SIVmac and human immunodeficiency virus type 1 Gag DNA immunization and identification of novel T-cell epitopes in mice via codon optimization

2009 ◽  
Vol 90 (10) ◽  
pp. 2513-2518 ◽  
Author(s):  
Christine S. Siegismund ◽  
Oliver Hohn ◽  
Reinhard Kurth ◽  
Stephen Norley
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
B Cell ◽  
Simian Immunodeficiency Virus ◽  
Codon Optimization ◽  
T Cell Epitopes ◽  
Gm Csf ◽  
Cell Responses ◽  
Immunodeficiency Virus

As a prelude to primate studies, the immunogenicity of wild-type and codon-optimized versions of simian immunodeficiency virus (SIV)agm Gag DNA, with and without co-administered granulocyte–macrophage colony-stimulating factor (GM-CSF) DNA, was directly compared in two strains of mice. Gag-specific T cells in the splenocytes of BALB/c and C57BL/6 mice immunized by gene gun were quantified by ELISpot using panels of overlapping synthetic peptides (15mers) spanning the entire capsid proteins of SIVagm, SIVmac and human immunodeficiency virus type 1. Specific antibodies were measured by ELISA. Codon optimization was shown to significantly increase the immune response to the DNA immunogens, reducing the amount of DNA necessary to induce cellular and antibody responses by one and two orders of magnitude, respectively. Co-administration of murine GM-CSF DNA was necessary for the induction of high level T- and B-cell responses. Finally, it was possible to identify both known and novel T-cell epitopes in the Gag proteins of the three viruses.

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