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1.
Immunity, inflammation and disease ; 10(6), 2022.
Article in English | EuropePMC | ID: covidwho-1863782

ABSTRACT

Background To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP‐CorV, we investigated immune responses in a cohort of Sri Lankan individuals. Methods SARS‐CoV‐2 specific total antibodies were measured in 20–39 years (n = 61), 40–59 years (n = 120) and those >60 years of age (n = 22) by enzyme‐linked immunosorbent assay, 12 weeks after the second dose of the vaccine. Angiotensin‐converting enzyme 2 (ACE2) receptor blocking antibodies (ACE2R‐Ab), antibodies to the receptor‐binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays. Results A total of 193/203 (95.07%) of individuals had detectable SARS‐CoV‐2 specific total antibodies, while 67/110 (60.9%) had ACE2R‐Ab. A total of 14.3%–16.7% individuals in the 20–39 age groups had detectable antibodies to the RBD of the WT and variants of concern, while the positivity rates of those ≥60 years of age was <10%. A total of 14/49 (28.6%) had Interferon gamma ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R‐Ab declined from 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R‐Ab levels was significant among the 40–59 (p = .0007) and ≥60 (p = .005) age groups. Conclusions Antibody responses declined in all age groups, especially in those ≥60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies. We have described the immune responses to the Sinopharm/BBIBP‐CorV vaccine, 12 weeks following the second dose of the vaccine. We show that while the SARS‐CoV‐2 specific total antibodies, and especially ACE2 receptor blocking antibodies and antibodies to the RBD significantly decline, the memory T cell and B cell responses persisted. Since the ACE2 receptor blocking antibodies was shown to significantly decline in all age groups and especially in the elderly.

2.
Immun Inflamm Dis ; 10(6): e621, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1850062

ABSTRACT

BACKGROUND: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. METHODS: SARS-CoV-2 specific total antibodies were measured in 20-39 years (n = 61), 40-59 years (n = 120) and those >60 years of age (n = 22) by enzyme-linked immunosorbent assay, 12 weeks after the second dose of the vaccine. Angiotensin-converting enzyme 2 (ACE2) receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor-binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays. RESULTS: A total of 193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. A total of 14.3%-16.7% individuals in the 20-39 age groups had detectable antibodies to the RBD of the WT and variants of concern, while the positivity rates of those ≥60 years of age was <10%. A total of 14/49 (28.6%) had Interferon gamma ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined from 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40-59 (p = .0007) and ≥60 (p = .005) age groups. CONCLUSIONS: Antibody responses declined in all age groups, especially in those ≥60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , Humans , Infant , Middle Aged , SARS-CoV-2
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331237

ABSTRACT

Background: With the onset of the COVID-19 pandemic in early 2020 there was a drastic reduction in the number of dengue cases in Sri Lanka, with an increase towards the end of 2021. We sought to study the contribution of virological factors, human mobility, school closure and mosquito factors in affecting these changes in dengue transmission in Sri Lanka during this time. Methods and findings: To understand the reasons for the differences in the dengue case numbers in 2020 to 2021 compared to previous years, we determined the association between the case numbers in Colombo (which has continuously reported the highest number of cases) with school closures, stringency index, changes in dengue virus (DENV) serotypes and vector densities. There was a 79.4% drop in dengue cases from 2019 to 2020 in Colombo. A significant negative correlation was seen with the number of cases and school closures (Spearman’s r=-0.4732, p=<0.0001) and a negative correlation, which was not significant, between the stringency index and case numbers (Spearman’s r= -0.3755 p=0.0587). There was no change in the circulating DENV serotypes with DENV2 remaining the most prevalent serotype by early 2022 (65%), similar to the frequencies observed by end of 2019. The Aedes aegypti premise and container indices showed positive but insignificant correlations with dengue case numbers (Spearman r= 0.8827, p=0.93). Conclusions: Lockdown measures, especially school closures seemed to have had a significant impact on the number of dengue cases, while the vector indices had a limited effect.

4.
Immun Inflamm Dis ; 10(4): e592, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763237

ABSTRACT

BACKGROUND: To 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. METHODS: Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled 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-blocking antibodies (ACE2-blocking Abs), antibodies to the receptor-binding domain (RBD) of  variants of concern (VOC), and ex vivo T cell responses were assessed in a subcohort. RESULTS: All individuals (100%) had SARS-CoV-2-specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2-blocking Abs. There was no difference in antibody titers or positivity rates in different age groups in both cohorts. The ACE2-blocking Abs (p < .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 hemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6%-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 interferon (IFN)γ ELISpot responses above the positive threshold. The ACE2-blocking antibodies (Spearman's r = .46, p = .008) and ex vivo IFNγ responses (Spearman's r = .71, p < .0001) at 12 weeks post first dose, significantly correlated with levels 12 weeks post second dose. CONCLUSIONS: Both dosing schedules resulted in high 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.


Subject(s)
COVID-19 , Vaccines , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunity , Kinetics , SARS-CoV-2 , Sri Lanka
5.
BMC Infect Dis ; 22(1): 276, 2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1759708

ABSTRACT

BACKGROUND: SARS-CoV-2 rapid antigen (Ag) detection kits are widely used in addition to quantitative reverse transcription PCR PCR (RT-qPCR), as they are cheaper with a rapid turnaround time. As there are many concerns regarding their sensitivity and specificity, in different settings, we evaluated two WHO approved rapid Ag kits in a large cohort of Sri Lankan individuals. METHODS: Paired nasopharangeal swabs were obtained from 4786 participants for validation of the SD-Biosensor rapid Ag assay and 3325 for the Abbott rapid Ag assay, in comparison to RT-qPCR. A short questionnaire was used to record symptoms at the time of testing, and blood samples were obtained from 2721 of them for detection of SARS-CoV-2 specific antibodies. RESULTS: The overall sensitivity of the SD-Biosensor Ag kit was 36.5% and the Abbott Ag test was 50.76%. The Abbott Ag test showed specificity of 99.4% and the SD-Biosensor Ag test 97.5%. At Ct values < 25, the sensitivity was 71.3% to 76.6% for the SD-Biosensor Ag test and 77.3% to 88.9% for the Abbott Ag test. The Ct values for all genes (RdRP, S, E and N) tested with all RT-qPCR kits were significantly lower for the positive results of the Abbott Ag test compared to the SD-Biosensor test. 209 (48.04%) individuals who had antibodies gave a positive RT-qPCR result, and antibody positivity rates were higher at Ct values > 30 (46.1 to 82.9%). 32.1% of those who gave a positive result with the SD-Biosensor Ag test and 26.3% of those who gave positive results with the Abbott Ag test had SARS-CoV-2 antibodies at the time of detection. CONCLUSIONS: Both rapid Ag tests appeared to be highly sensitive in detecting individuals at lower Ct values, in a community setting in Sri Lanka, but it will be important to further establish the relationship to infectivity.


Subject(s)
COVID-19 , RNA, Viral , Antibodies, Viral , COVID-19/diagnosis , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , World Health Organization
6.
Clin Exp Immunol ; 208(3): 323-331, 2022 Jun 23.
Article in English | MEDLINE | ID: covidwho-1746941

ABSTRACT

To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222 (Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD, and N proteins in patients at 4 weeks and 12 weeks since the onset of illness or following vaccination. Antibodies to the receptor-binding domain of SARS-CoV-2 wild type (WT), α, ß, and λ and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. For those with mild illness and in vaccines, the IgG responses to S1, S2, RBD, and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccines, IgG antibodies to the S2 subunit had the highest significant rise (P < 0.0001). Vaccines had several-fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the haemagglutination test (HAT) titres were significantly lower to the α in vaccines and significantly lower in those with mild illness and in vaccines to ß and for λ. No such difference was seen in those with moderate/severe illness. Vaccines had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccines had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs.

7.
Allergy Asthma Clin Immunol ; 17(1): 67, 2021 Jul 08.
Article in English | MEDLINE | ID: covidwho-1690881

ABSTRACT

BACKGROUND: A significant portion of COVID-19 sufferers have asthma. The impacts of asthma on COVID-19 progression are still unclear but a modifying effect is plausible as respiratory viruses are acknowledged to be an important trigger for asthma exacerbations and a different, potentially type-2 biased, immune response might occur. In this study, we compared the blood circulating cytokine response to COVID-19 infection in patients with and without asthma. METHODS: Plasma samples and clinical information were collected from 80 patients with mild (25), severe (36) or critical (19) COVID-19 and 29 healthy subjects at the John Radcliffe Hospital, Oxford, UK. The concentrations of 51 circulating proteins in the plasma samples were measured with Luminex and compared between groups. RESULTS: Total 16 pre-existing asthma patients were found (3 in mild, 10 in severe, and 3 in critical COVID-19). The prevalence of asthma in COVID-19 severity groups did not suggest a clear correlation between asthma and COVID-19 severity. Within the same COVID-19 severity group, no differences were observed between patients with or without asthma on oxygen saturation, CRP, neutrophil counts, and length of hospital stay. The mortality in the COVID-19 patients with asthma (12.5%) was not higher than that in patients without asthma (17.2%). No significant difference was found between asthmatic and non-asthmatic in circulating cytokine response in different COVID-19 severity groups, including the cytokines strongly implicated in COVID-19 such as CXCL10, IL-6, CCL2, and IL-8. CONCLUSIONS: Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313283

ABSTRACT

In order to support vaccine development, and to aid convalescent plasma therapy, it would be important to understand the kinetics, timing and persistence of SARS-CoV2 neutralizing antibodies (NAbs), and their association with clinical disease severity. Therefore, we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points.Patients with severe or moderate COVID-19 illness had earlier appearance of NAbs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had NAbs appearing faster and at higher levels than those who cleared the virus earlier. During the first week of illness the NAb levels of those with mild illness was significantly less (p=0.01), compared to those with moderate and severe illness. At the end of 4 weeks (28 days), although 89% had Nabs, 38/76 (50%) in those with >90 days had a negative result for the presence of NAbs. The Ab levels significantly declined during convalescence (>90 days since onset of illness), compared to 4 to 8 weeks since onset of illness. Our data show that high levels of NAbs during early illness associated with clinical disease severity and that these antibodies declined in 50% of individuals after 3 months since onset of illness.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313282

ABSTRACT

Background: SARS-CoV-2 rapid antigen (Ag) detection kits are widely used in addition to quantitative real-time PCR (RT-qPCR), as they are cheaper with a rapid turnaround time. As there are many concerns regarding their sensitivity and specificity, in different settings, we evaluated two WHO approved rapid Ag kits in a large cohort of Sri Lankan individuals. Methods: : Paired nasopharangeal swabs were obtained from 4845 participants for validation of the SD-Biosensor rapid Ag assay and 3625 for the Abbott rapid Ag assay, in comparison to RT-qPCR. A short questionnaire was used to record symptoms at the time of testing, and blood samples were obtained from 2721 of them for detection of SARS-CoV-2 specific antibodies. Results: : The overall sensitivity of the SD-Biosensor Ag kit was 36.5% and the Abbott Ag test was 50.76%. The Abbott Ag test showed specificity of 99.4% and the SD-Biosensor Ag test 97.5%. At Ct values <25, the sensitivity was 71.3% to 76.6% for the SD-Biosensor Ag test and 77.3% to 88.9% for the Abbott Ag test. The Ct values for all genes (RdRP, S, E and N) tested with all RT-qPCR kits were significantly lower for the positive results of the Abbott Ag test compared to the SD-Biosensor test. 209 (48.04%) individuals who had antibodies gave a positive RT-qPCR result, and antibody positivity rates were higher at Ct values >30 (46.1 to 82.9%). 32.1% of those who gave a positive result with the SD-Biosensor Ag test and 26.3% of those who gave positive results with the Abbott Ag test had SARS-CoV-2 antibodies at the time of detection. Conclusions: : Both rapid Ag tests appeared to be highly sensitive in detecting individuals at lower Ct values, in a community setting in Sri Lanka, but it will be important to further establish the relationship to infectivity.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313281

ABSTRACT

Background: As the first dose of Sputnik V Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of a single dose of this vaccine in Sri Lankan adults at 4 weeks and compared the immune responses with our previously published data following AZD1222.Methods: SARS-CoV-2 antibodies were assessed at 504 individuals at the time of recruitment and at 4 weeks since receiving the single dose in Sri Lankan adults. ACE2 receptor blocking antibodies, antibodies to the receptor binding domain (RBD) of variants of concern, ex vivo IFNγ ELISpot responses, intracellular cytokine assays and B cell ELISpot assays were carried out in a sub-cohort.Findings: Of the 327/504 individuals who were baseline seronegative, 88.7% seroconverted, with significantly lower seroconversion rates in those >60-years old (p-value = 0.004) and significantly lower than previously seen with AZD1222 (p=0.018). 82.6% developed ACE2 receptor blocking antibodies, although the levels were significantly lower than seen following natural infection (p=0.0009) and following a single dose of AZD1222 (p<0.0001). Similar titres of antibodies were observed to the RBD of the 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% of individuals developed ex vivo IFNγ ELISpot responses, and high frequency of CD107a expressing T cells along with memory B cell responses. The ex vivo IFNγ responses for spike protein were significantly higher (p<0.0001) for AZD1222 than for Gam-COVID-Vac.Interpretation: A single dose of Sputnik V Gam-COVID-Vac induced high seroconversion rates although lower responses in older age groups in Sri Lankan adults. The overall antibody responses, ACE2 receptor blocking antibody responses and ex vivo T cell responses appear to be significantly lower than previously seen with AZD1222, and so there is likely to be benefit from delivery of the second dose.Funding: We are grateful to the World Health Organization, UK Medical Research Council. theForeign and Commonwealth Office and NIH, USA (grant number 5U01AI151788-02) for support.T.K.T. is funded by the Townsend-Jeantet Charitable Trust (charity number 1011770) and the EPACephalosporin Early Career Researcher Fund.Declaration of Interest: None of the authors have any conflicts of interest.Ethical Approval: Ethics approval was obtained from the Ethics Review Committee of University of Sri Jayewardenepura (COVID 01/21).

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309642

ABSTRACT

NP 105-113 -B*07:02 specific CD8 + T-cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP 105-113 -B*07:02 specific T-cell clones and single cell sequencing were performed concurrently, with functional avidity and anti-viral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with TCR usage, transcriptome signature, and disease severity (acute N=77, convalescent N=52). We demonstrated a beneficial association of NP 105-113 -B*07:02 specific T-cells in COVID-19 disease progression, linked with expansion of T-cell precursors, high functional avidity and anti-viral effector function. Broad immune memory pools were narrowed post-infection but NP 105-113 -B*07:02 specific T-cells were maintained 6 months after infection with preserved anti-viral efficacy to the SARS-CoV-2 Victoria strain, as well as new Alpha, Beta and Gamma variants. Our data shows that NP 105-113 -B*07:02 specific T-cell responses associate with mild disease and high anti-viral efficacy, pointing to inclusion for future vaccine design.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309212

ABSTRACT

Severe pneumonia and multiorgan dysfunction in COVID-19 and dengue haemorrhagic fever (DHF) are two diseases that can associate with an altered immune response to the infecting virus. To determine the similarities and differences in the cytokine and chemokine responses in these two infections, we compared responses in patients with varying severity of COVID-19 and acute dengue at different time points of illness.During early disease, patients who proceeded to develop COVID-19 severe pneumonia (SP) and DHF had significantly higher levels of IL-6, IL-10 and MIP3α than those who developed mild illness. The lowest levels of IFNγ in early illness were seen in those who succumbed to their illness due to COVID-19. Levels of serum IL-10 (p=0.0001), IL-6 (p=0.002), MIP-3α (p=0.02) and CD40-L levels (p=0.002) significantly increased from 5-9 day of illness to 10-21 day of illness in patients with moderate-to-severe COVID-19, but not in those with mild illness. In contrast, these cytokine/chemokine levels remained unchanged in those with DHF or dengue fever (DF) during febrile and critical phases. Although IL-10 levels were significantly higher in COVID-19 patients with SP, patients with DHF had 25-fold higher levels, whereas IL-6 levels were 11-fold higher in those with COVID-19 SP. IL-10 and other cytokines were evaluated in a larger cohort of patients during early illness (≤ 4 days) who proceeded to develop DF (n=71) or DHF (n=64). Of the cytokines evaluated, IL-10 was significantly higher (p<0.0001) in those who went on to develop DHF compared to DF. Low IFNγ response to the SARS-CoV2 and high levels of immunosuppressive IL-10 in both COVID-19 and dengue during early illness are indicators of an altered antiviral response potentially contributing to disease severity.

13.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328783

ABSTRACT

Little is known of the role of cytotoxic CD4 + T-cells in the control of viral replication. Here, we investigate CD4 + T-cell responses to three dominant SARS-CoV-2 epitopes and evaluate antiviral activity, including cytotoxicity and antiviral cytokine production. Diverse T cell receptor (TCR) usage including public TCRs were identified;surprisingly, cytotoxic CD4 + T-cells were found to have signalling and cytotoxic pathways distinct from classical CD8 + T-cells, with increased expression of chemokines and tissue homing receptors promoting migration. We show the presence of cytolytic CD4 + T-cells during primary infection associates with COVID-19 disease severity. Robust immune memory 6-9 months post-infection or vaccination provides CD4 + T-cells with potent antiviral activity. Our data support a model where CD4 + killer cells drive immunopathogenesis during primary infection and CD4 + memory responses are protective during secondary infection. Our study highlights the unique features of cytotoxic CD4 + T-cells that use distinct functional pathways, providing preventative and therapeutic opportunities.

14.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327454

ABSTRACT

Background The worst SARS-CoV-2 outbreak in Sri Lanka was due to the two Sri Lankan delta sub-lineages AY.28 and AY.104. We proceeded to further characterize the mutations and clinical disease severity of these two sub-lineages. Methods 705 delta SARS-CoV-2 genomes sequenced by our laboratory from mid-May to November 2021 using Illumina and Oxford Nanopore were included in the analysis. The clinical disease severity of 440/705 individuals were further analyzed to determine if infection with either AY.28 or AY.104 was associated with more severe disease. Sub-genomic RNA (sg-RNA) expression was analyzed using periscope. Results AY.28 was the dominant variant throughout the outbreak, accounting for 67.7% of infections during the peak of the outbreak. AY.28 had three lineage defining mutations in the spike protein: A222V (92.80%), A701S (88.06%), and A1078S (92.04%) and seven in the ORF1a: R24C, K634N, P1640L, A2994V, A3209V, V3718A, and T3750I. AY.104 was characterized by the high prevalence of T95I (90.81%) and T572L (65.01%) mutations in the spike protein and by the absence of P1640L (94.28%) in ORF1a with the presence of A1918V (98.58%) mutation. The mean sgRNA expression levels of ORF6 in AY.28 were significantly higher compared to AY.104 (p < 0.0001) and B.1.617.2 (p < 0.01). Also, ORF3a showed significantly higher sgRNA expression in AY.28 compared to AY.104 (p < 0.0001). There was no difference in the clinical disease severity or duration of hospitalization in individuals infected with these sub lineages. Conclusions Therefore, AY.28 appears to have a fitness advantage over the parental delta variant (B.1.617.2) and AY.104 possibly due to the A222V mutation. AY.28 also had a higher expression of sg-RNA compared to other sub-lineages. The clinical implications of these should be further investigated.

15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319441

ABSTRACT

Background: Individuals who have not been exposed to the SARS-CoV2 virus have been shown to have T cells that respond to the virus, possibly due to the presence of cross-reactive T cell responses to other seasonal human coronaviruses (HCoVs). Such cross-reactive T cell immunity may lead to immunopathology or protection. Results To understand the influence of such cross-reactive T cell responses, we used IEDB (Immune epitope database) and NetMHCpan (ver. 4.1) to identify candidate CD8 + T cell epitopes, restricted through HLA-A and B alleles, which are seen in a frequency of > 10% in the Sri Lankan population. Conservation analysis was carried out for these candidate epitopes with the HCoVs, OC43, HKU1, NL63 and with the current circulating different variants of SARS-CoV2. 12/18 the candidate CD8 + T cell epitopes (binding score of ≥ 0.90), which had a high degree of homology (> 75%) with the other three HCoVs were within the NSP12 and NSP13 proteins. They were predicted to be restricted through HLA-A*2402, HLA-A*201, HLA-A*206 and HLA-B alleles B*3501. 31 candidate CD8 + T cell epitopes that were specific to SARS-CoV2 virus (< 25% homology with other HCoVs) were predominantly identified within the structural proteins (spike, envelop, membrane and nucleocapsid) and the NSP1, NSP2 and NSP3. They were predominantly restricted through HLA-B*3501 (6/31), HLA-B*4001 (6/31), HLA-B*4403(7/31) and HLA-A*2402 (8/31). The candidate CD8 + T cell epitopes that were homologous or were specific, with a binding score of ≥ 0.90, were found to be highly conserved within the SARS-CoV2 variants identified so far. Conclusions It would be crucial to understand T cell responses that associate with protection and the differences in the functionality and phenotype of epitope specific T cell responses, presented through different HLA alleles common in different geographical groups in order to understand disease pathogenesis.

16.
Immunology ; 166(1): 78-103, 2022 05.
Article in English | MEDLINE | ID: covidwho-1685321

ABSTRACT

The conditions and extent of cross-protective immunity between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common-cold human coronaviruses (HCoVs) remain open despite several reports of pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure. Using a pool of functionally evaluated SARS-CoV-2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC-presented peptides from at least one HCoV. Employing this map of SARS-CoV-2-non-homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID-19 patients. After combining our map with SARS-CoV-2-specific TCR repertoire data from COVID-19 patients and healthy controls, we show that public repertoires for the majority of convalescent patients are dominated by TCRs cognate to non-homologous SARS-CoV-2 peptides. We find that for a subset of patients, >50% of their public SARS-CoV-2-specific repertoires consist of TCRs cognate to homologous SARS-CoV-2-HCoV peptides. Further analysis suggests that this skewed distribution of TCRs cognate to homologous or non-homologous peptides in COVID-19 patients is likely to be HLA-dependent. Finally, we provide 10 SARS-CoV-2 peptides with known cognate TCRs that are conserved across multiple coronaviruses and are predicted to be recognized by a high proportion of the global population. These findings may have important implications for COVID-19 heterogeneity, vaccine-induced immune responses, and robustness of immunity to SARS-CoV-2 and its variants.


Subject(s)
COVID-19 , SARS-CoV-2 , CD8-Positive T-Lymphocytes , Cross Reactions , Epitopes, T-Lymphocyte , Humans , Peptides , Receptors, Antigen, T-Cell , Spike Glycoprotein, Coronavirus
17.
Clinical and experimental immunology ; 2022.
Article in English | EuropePMC | ID: covidwho-1678899

ABSTRACT

To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222(Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD and N proteins in patients at 4 weeks and 12 weeks since onset of illness or following vaccination. Antibodies to the receptor binding domain of SARS-CoV-2 wild type (WT), alpha, beta and delta and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. Those with mild illness and in vaccinees, the IgG responses to S1, S2, RBD and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccinees, IgG antibodies to the S2 subunit had the highest significant rise(p<0.0001). Vaccinees had several fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the Haemagglutination test (HAT) titres were significantly lower to the alpha in vaccinees and significantly lower in those with mild illness and in vaccinees to beta and for delta. No such difference was seen in those with moderate/severe illness. Vaccinees had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccinees had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs.

18.
Sci Rep ; 12(1): 1727, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-1671625

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.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Vaccines, Synthetic/administration & dosage , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/immunology , Biomarkers/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Female , Humans , Interferon-gamma/metabolism , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/virology , Male , Middle Aged , Seroconversion , Time Factors , Treatment Outcome , Vaccines, Synthetic/immunology , Young Adult
19.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296735

ABSTRACT

We assessed antibody responses 3 months post-vaccination in those who received mRNA-1273 (n=225), Sputnik V (n=128) or the first dose of Gam-COVID-Vac (n=184) and compared the results with previously reported data of Sinopharm and AZD1222 vaccinees. 99.5% of Moderna >94% of AZD1222 or Sputnik V, 72% to 76% of Gam-COVID-Vac (first dose) and 38.1% to 68.3% of Sinopharm vaccinees had ACE2 blocking antibodies above the positive threshold. The ACE2 blocking antibody levels were highest to lowest was Moderna > Sputnik V/ AZD1222 (had equal levels)> first dose of Gam-COVID-Vac > Sinopharm. All Moderna recipients had antibodies above the positive threshold to the ancestral (WT), B.1.1.7, B.1.351.1 and 80% positivity rate for B.1.617.2. Positivity rates of Sputnik V vaccinees for WT and variants, were higher than AZD1222 vaccinees, while Sinopharm vaccinees had the lowest positivity rates (<16.7%). These findings highlight the need for further studies to understand the effects on clinical outcomes.

20.
Front Public Health ; 9: 724398, 2021.
Article in English | MEDLINE | ID: covidwho-1555557

ABSTRACT

Background: As the Municipality Council area in Colombo (CMC) experienced the highest number of cases until the end of January 2021, in Sri Lanka, we carried out a serosurvey prior to initiation of the vaccination program to understand the extent of the SARS-CoV-2 outbreak. Methods: SARS-CoV-2 seropositivity was determined in 2,547 individuals between the ages of 10-86 years, by the Wantai total antibody ELISA. We also compared seroprevalence using the haemagglutination test (HAT) to evaluate its usefulness in carrying out serosurveys. Results: The overall seropositivity rate was 24.46%, while seropositivity by HAT was 18.90%. Although The SARS-CoV-2 infection detection rates by PCR were highest in the population between the ages of 20-60 years of age, there was no statistically significant difference in the seropositivity rates in different age groups. For instance, although the seropositivity rate was highest in the 10-20 age group (34.03%), the PCR positivity rate was 9.80%. Differences in the PCR positivity rates and seropositivity rates were also seen in 60-70-year-olds (8.90 vs. 30.4%) and in individuals >70 years (4.10 vs. 1.20%). The seropositivity rate of the females was 29.70% (290/976), which was significantly higher (p < 0.002) than in males 21.2% (333/1,571). Conclusions: A high seroprevalence rate (24.5%) was seen in all age groups in the CMC suggesting that a high level of transmission was seen during this time. The higher PCR positivity rates between the ages of 20-60 are likely to be due to increased testing carried out in the working population. Therefore, the PCR positivity rates, appear to underestimate the true extent of the outbreak and the age groups which were infected.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , Child , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Seroepidemiologic Studies , Sri Lanka/epidemiology , Young Adult
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