scholarly journals Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac)

2021 ◽  
Author(s):  
Gathsaurie Malavige ◽  
Chandima Jeewandara ◽  
Harsha Fernando ◽  
Pradeep Darshana Pushpakumara ◽  
Shyrar Tanussiya ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
High Frequency ◽  
Ex Vivo ◽  
Natural Infection ◽  
Receptor Binding Domain ◽  
Cell Responses ◽  
Blocking Antibodies ◽  
With Memory ◽  
Dose Vaccine

Abstract As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.

scholarly journals Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac)

2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Harsha Fernando ◽  
Pradeep Pushpakumara ◽  
Shyrar Tanussiya ◽  
Achala Kamaladasa ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
High Frequency ◽  
Ex Vivo ◽  
Natural Infection ◽  
Receptor Binding Domain ◽  
Cell Responses ◽  
Blocking Antibodies ◽  
With Memory ◽  
Dose Vaccine

Abstract As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.

scholarly journals Immune responses to a single dose of the AZD1222/Covishield vaccine at 16 weeks in individuals in Sri Lanka

2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Dinuka Guruge ◽  
Pradeep Pushpakumara ◽  
Achala Kamaladasa ◽  
Inoka Aberathna ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
B Cell ◽  
High Frequency ◽  
Ex Vivo ◽  
P Value ◽  
Receptor Blocking ◽  
Specific Antibodies ◽  
Cell Responses ◽  
Blocking Antibodies

Introduction: Due to limited access to vaccines, many countries have only administered a single dose of the AZD1222, while the dosage intervals have increased ≥ weeks. We sought to investigate the immunogenicity of a single dose of vaccine at ≥ 16 weeks. Methods: SARS-CoV-2 specific antibodies in 553 individuals and antibodies to the receptor binding domain (RBD) of the Wuhan virus (WT) and the variants of concern (VOCs), ACE2 receptor blocking antibodies, ex vivo and cultured IFNγ T cell responses and B cell ELISpot responses were investigated in a sub-cohort. Results: The seropositivity rates in those >70 years of age (93.7%) was not significantly different compared to other age groups (97.7 to 98.2, Pearson Chi-Square = 7.8, p-value = 0.05). The antibody titres (antibody index) significantly declined (p<0.0001) with increase in age. 18/69 (26.1%) of individuals did not have ACE2 receptor blocking antibodies, while responses to the RBD of WT (p=0.03), B.1.1.7 (p=0.04) and B.1.617.2 (p=0.02) were significantly lower in those who were >60 years. Ex vivo IFN γ T cell ELISpot responses were seen in 10/66 (15.1%), while only a few expressed CD107a. However, >85% had a high frequency of cultured IFNγ T cell ELISpot responses and B cell ELISpots. Conclusion: Virus specific antibodies were maintained at ≥ 16 weeks after receiving a single dose of AZD1222, although levels were lower to VOCs, especially in older individuals. A single dose induced a high frequency of memory T and B cell responses.

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 Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cells ◽  
Single Dose ◽  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
T Cell Response ◽  
High Potency ◽  
Cell Responses ◽  
Reference Isolate ◽  
High Magnitude

AbstractThe extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.

scholarly journals Immune responses to inactivated and vector-based vaccines in individuals previously infected with SARS-CoV-2

2022 ◽  
Author(s):  
Nungruthai Suntronwong ◽  
Ritthideach Yorsaeng ◽  
Chompoonut Auphimai ◽  
Thanunrat Thongmee ◽  
Preeyaporn Vichaiwattana ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Dose ◽  
Immune Responses ◽  
Antibody Response ◽  
Specific Binding ◽  
Specific Antibodies ◽  
Neutralizing Activity ◽  
Cell Responses ◽  
Interferon Gamma Response ◽  
Dose Vaccine

AbstractImmunity wanes in individuals previously infected with SARS-CoV-2, and vaccinating those individuals may help reduce reinfection. Herein, reactogenicity and immunogenicity following vaccination with inactivated (CoronaVac) and vector-based (ChAdOx1-S, AZD1222) vaccines were examined in previously infected individuals. Immune response was also compared between short and long intervals between first date of detection and vaccination. Adverse events were mild but were higher with AZD1222 than with CoronaVac. Baseline IgG-specific antibodies and neutralizing activity were significantly higher with shorter than longer intervals. With a single-dose vaccine, IgG and IgA-specific binding antibodies, neutralizing activity, and total interferon-gamma response peaked at 14 days. Immune response was significantly higher in recovered individuals than in infection-naïve individuals. Antibody response was greater with longer than shorter intervals. AZD1222 induced higher antibody and T cell responses than those of CoronaVac. Thus, to achieve immunity, individuals with prior SARS-CoV-2 exposure may require only a single dose of AZD1222 or two doses of CoronaVac to achieve the immune response. These findings supported vaccine strategies in previously infected individuals.

scholarly journals Antibody and T-cell responses to a single dose of the AZD1222/Covishield vaccine in previously SARS-CoV-2 infected and naive health care workers in Sri Lanka

2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Achala Kamaladasa ◽  
Pradeep D Pushpakumara ◽  
Deshni Jayathilaka ◽  
Inoka Sepali ◽  
...  
Keyword(s):  
Health Care ◽  
Single Dose ◽  
T Cell ◽  
Health Care Workers ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Wild Type Virus ◽  
Cell Responses ◽  
Care Workers ◽  
Blocking Antibodies

Background: In order to determine the immunogenicity of a single dose of the AZD1222/Covishield vaccine in a real-world situation, we assessed the immunogenicity, in a large cohort of health care workers in Sri Lanka. Methods: SARS-CoV-2 antibodies was carried out in 607 naive and 26 previously infected health care workers (HCWs) 28 to 32 days following a single dose of the vaccine. Haemagglutination test (HAT) for antibodies to the receptor binding domain (RBD) of the wild type virus, B.1.1.7, B.1.351 and the surrogate neutralization assay (sVNT) was carried out in 69 naive and 26 previously infected individuals. Spike protein (pools S1 and S2) specific T cell responses were measured by ex vivo ELISpot IFNg; assays in 76 individuals. Results: 92.9% of previously naive HCWs seroconverted to a single dose of the vaccine, irrespective of age and gender; and ACE2 blocking antibodies were detected in 67/69 (97.1%) previously naive vaccine recipients. Although high levels of antibodies were found to the RBD of the wild type virus, the titres for B.1.1.7 and B.1.351 were lower in previously naive HCWs. Ex vivo T cell responses were observed to S1 in 63.9% HCWs and S2 in 31.9%. The ACE2 blocking titres measured by the sVNT significantly increased (p<0.0001) from a median of 54.1 to 97.9 % of inhibition, in previously infected HCWs and antibodies to the RBD for the variants B.1.1.7 and B.1.351 also significantly increased. Discussion: a single dose of the AZD1222/Covishield vaccine was shown to be highly immunogenic in previously naive individuals inducing antibody levels greater than following natural infection. In infected individuals, a single dose induced very high levels of ACE2 blocking antibodies and antibodies to RBDs of SARS-CoV-2 variants of concern.

scholarly journals Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals

2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Inoka Sepali Aberathna ◽  
Laksiri Gomes ◽  
Pradeep Darshana Pushpakumara ◽  
Saubhagya Danasekara ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Positive Response ◽  
Ex Vivo ◽  
Age Groups ◽  
T Cell Responses ◽  
Cell Responses ◽  
Antibody Titres ◽  
Blocking Antibodies ◽  
Kinetics Of

AbstractBackgroundTo understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps.MethodsAntibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled at 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2 receptor blocking antibodies (ACE2R-Abs), antibodies to the receptor binding domain (RBD) of the virus and variants of concern (VOC) and ex vivo T cell responses were assessed in a sub cohort.ResultsAll individuals (100%) had SARS-CoV-2 specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2R-blocking Abs. There was no difference in antibody titres or positivity rates in different age groups in both cohorts. The ACE2R-blocking Abs (p<0.0001) and antibodies to the RBD of the VOCs were significantly higher in cohort 2, compared to cohort 1. 41.2% to 65.8% of different age groups gave a positive response by the haemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6% to 90% gave a positive response in cohort 2. 17/57 (29.8%) of cohort 1 and 17/29 (58.6%) of cohort 2 had ex vivo IFNγ ELISpot responses above the positive threshold. The ACE2R-blocking antibodies and ex vivo IFNγ ELISpot responses at 12 weeks post-first dose, significantly correlated with levels 12 weeks post second dose (Spearman’s r=0.46, p=0.008) and (Spearman’s r=0.71, p<0.0001) respectively.ConclusionsBoth dosing schedules resulted in high levels of antibody and T cell responses post vaccination, although those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose.

scholarly journals 413 GEN-009, a personalized neoantigen vaccine, elicits robust immune responses in individuals with advanced or metastatic solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A438-A438
Author(s):  
Mara Shainheit ◽  
Devin Champagne ◽  
Gabriella Santone ◽  
Syukri Shukor ◽  
Ece Bicak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Solid Tumors ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Checkpoint Blockade ◽  
T Cell Subsets ◽  
Cell Responses

BackgroundATLASTM is a cell-based bioassay that utilizes a cancer patient‘s own monocyte-derived dendritic cells and CD4+ and CD8+ T cells to screen their mutanome and identify neoantigens that elicit robust anti-tumor T cell responses, as well as, deleterious InhibigensTM.1 GEN-009, a personalized vaccine comprised of 4–20 ATLAS-identified neoantigens combined with Hiltonol®, harnesses the power of neoantigen-specific T cells to treat individuals with solid tumors. The safety and efficacy of GEN-009 is being assessed in a phase 1/2a clinical trial (NCT03633110).MethodsA cohort of 15 adults with solid tumors were enrolled in the study. During the screening period, patients received standard of care PD-1-based immunotherapies appropriate for their tumor type. Subsequently, patients were immunized with GEN-009 with additional doses administered at 3, 6, 12, and 24 weeks. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, pre-vaccination (D1), as well as 29, 50, 92, and 176 days post first dose. Vaccine-induced immunogenicity and persistence were assessed by quantifying neoantigen-specific T cell responses in ex vivo and in vitro stimulation dual-analyte fluorospot assays. Polyfunctionality of neoantigen-specific T cells was evaluated by intracellular cytokine staining. Additionally, potential correlations between the ATLAS-identified profile and vaccine-induced immunogenicity were assessed.ResultsGEN-009 augmented T cell responses in 100% of evaluated patients, attributable to vaccine and not checkpoint blockade. Furthermore, neoantigen-induced secretion of IFNγ and/or TNFα by PBMCs, CD4+, and CD8+ T cells was observed in all patients. Responses were primarily from polyfunctional TEM cells and detectable in both CD4+ and CD8+ T cell subsets. Some patients had evidence of epitope spreading. Unique response patterns were observed for each patient with no apparent relationship between tumor types and time to emergence, magnitude or persistence of response. Ex vivo vaccine-induced immune responses were observed as early as 1 month, and in some cases, persisted for 176 days. Clinical efficacy possibly attributable to GEN-009 was observed in several patients, but no correlation has yet been identified with neoantigen number or magnitude of immune response.ConclusionsATLAS empirically identifies stimulatory neoantigens using the patient‘s own immune cells. GEN-009, which is comprised of personalized, ATLAS-identified neoantigens, elicits early, long-lasting and polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses in individuals with advanced cancer. Several patients achieved clinical responses that were possibly attributable to vaccine; efforts are underway to explore T cell correlates of protection. These data support that GEN-009, in combination with checkpoint blockade, represents a unique approach to treat solid tumors.AcknowledgementsWe are grateful to the patients and their families who consented to participate in the GEN-009-101 clinical trial.Trial RegistrationNCT03633110Ethics ApprovalThis study was approved by Western Institutional Review Board, approval number 1-1078861-1. All subjects contributing samples provided signed individual informed consent.ReferenceDeVault V, Starobinets H, Adhikari S, Singh S, Rinaldi S, Classon B, Flechtner J, Lam H. Inhibigens, personal neoantigens that drive suppressive T cell responses, abrogate protection of therapeutic anti-tumor vaccines. J. Immunol 2020; 204(1 Supplement):91.15.

scholarly journals Immunogenicity of mRNA-1273, BNT162b2 and Ad26.COV2.S COVID-19 vaccines

2021 ◽  
Author(s):  
Vivek Naranbhai ◽  
Wilfredo F Garcia-Beltran ◽  
Christhian Berrios Mairena ◽  
Julia Cara Thierauf ◽  
Christina Catherine Chang ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Control Groups ◽  
Neutralization Titer ◽  
Cell Responses ◽  
Effectiveness Studies ◽  
Prior Infection ◽  
Repeat Sampling

Background: Understanding variation in immunogenicity may help rationalize use of existing SARS-CoV-2 vaccines. Methods: We compared immune responses in ambulatory adults vaccinated with mRNA-1273 , BNT-162b2 or Ad26.COV2.S in Massachusetts, USA between February and May 2021. Control groups were pre-pandemic controls (n=1220) and individuals without (n=112) or with prior SARS-CoV-2 infection (n=130) sampled in mid-2020. We measured total anti-spike IgG/M/A antibodies (Roche Elecsys Anti-SARS-COV-2 S assay), anti-receptor-binding-domain (RBD) antibodies; neutralization of SARS-CoV-2 pseudovirus; and T-cell responses. Findings In individuals with prior infection, all vaccines were associated with higher antibody concentrations and neutralization than those in convalescent individuals, even after a single dose. In individuals without prior infection, a single dose of either mRNA vaccine yielded comparable concentrations and neutralization to convalescent unvaccinated individuals, and Ad26.COV2.S yielded lower antibody concentrations and neutralization titers. The second dose of either mRNA vaccine boosted responses. At a median of 24 days after vaccination, two of 21 (9.5%) Ad26.COV2.S recipients had a neutralization titer higher than pre-pandemic controls; repeat sampling at a median 66 days after vaccination found most (11/15 (73%) remained negative. Antibody concentrations and neutralization titers increased similarly after the first dose of either vaccine, and even further in recipients of a second dose of vaccine. T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients. Interpretation SARS-CoV-2 vaccines vary significantly in immunogenicity in individuals without prior infection. If confirmed in effectiveness studies, public health policy may need to be tailored to each vaccine, or even individual responses.

scholarly journals Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection

2020 ◽  
Author(s):  
Jianmin Zuo ◽  
Alex Dowell ◽  
Hayden Pearce ◽  
Kriti Verma ◽  
Heather Long ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Antibody Level ◽  
Primary Infection ◽  
Natural Infection ◽  
T Cell Responses ◽  
Symptomatic Infection ◽  
Cell Responses ◽  
Cell Immunity

Abstract The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection.

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