ChAdOx1 nCoV-19 Research Articles

Understanding Factors Responsible for Delay and Non-Compliance in COVID-19 Vaccination at a Tertiary Care Hospital in Mumbai, India

Background: Despite extensive first-dose coverage, delays in second doses and late first doses prompted a study on vaccine hesitancy and non-compliance. Methods: In 2022, a cross-sectional survey was conducted at a Mumbai vaccination center, involving 504 individuals who had received either the first or second dose of the COVID-19 vaccine. The study, conducted from February to April 2022, included interviews using a pre-validated schedule to assess vaccine acceptance, refusal, socio-demographics, and reasons for hesitancy. Data analysis was performed using IBM SPSS Statistics software 23.0 to understand factors influencing vaccine delay and non-compliance. Result: The study interviewed 504 participants at a Mumbai vaccination center. Most were male (63.9%), aged 18-44 (80%), and skilled workers (22.6%). Of those surveyed, 64 had received only the first vaccine dose. The delay in receiving the second dose was 37.4% for BBV152 and 41% for ChAdOx1 nCoV-19. The primary reason for delay was lack of time (50.6%), followed by fear of the vaccine (14.8%). Reasons for getting vaccinated later included resolving constraints (40.5%) and compulsion (25.8%). Vaccine choice reasons varied significantly (p < 0.0005), but delay proportions were similar across vaccines (p = 0.531). Conclusion: Even after many efforts by the government, large numbers of people have not taken vaccine on time. One of the reasons, as seen in the study is a busy work schedule which has hindered timely vaccination in individuals. Making vaccine available at work place may address this issue to some extent, besides ownership of the program by the public.

Levels of high-sensitive troponin T and mid-regional pro-adrenomedullin after COVID-19 vaccination in vulnerable groups: monitoring cardiovascular safety of COVID-19 vaccination

BackgroundCOVID-19 vaccines are well tolerated and effective but may have adverse effects on the cardiovascular system. Vaccine-associated myocardial injury was analysed by measuring high-sensitive troponin T (hsTnT); mid-regional pro-adrenomedullin (MR-proADM) levels were evaluated to assess endothelial dysfunction.MethodsThis was a prospective study with a vulnerable population of healthcare workers (HCWs) and elderly patients (>70 years) who were vaccinated with either one dose of ChAdOx1 nCov-19 adenoviral vector vaccine (AZ) followed by one dose of the BNT162b2 messenger RNA vaccine (BNT), or with two doses of BNT (12th of January - 30th of November 2021). HsTnT and MR-proADM were measured in blood samples at three visits (V1: 1st immediately before vaccination; V2, 3: 3–4 weeks after 1st and 2nd vaccination). HsTnT of HCWs was compared to a healthy reference population.ResultsN = 162 volunteers were included (V1 = 161; V2, V3 = 162 each). N = 74 (45.7%) received AZ/BNT and n = 88 (54.3%) received BNT/BNT [elderly: n = 20 (12.3%), HCWs: n = 68 (42.0%)]. Median hsTnT levels were 4 ng/L, 5 ng/L and 4 ng/L (V1-V3) for AZ/BNT and at 5 ng/L, 6 ng/L and 6 ng/L (V1-V3) for BNT/BNT. Compared to the reference population (n = 300), hsTnT was significantly higher at all visits for both vaccination groups (p < 0.01), without differences between the AZ/BNT and BNT/BNT cohort. Median MR-proADM values were 0.43 nmol/L, 0.45 nmol/L, 0.44 nmol/L (V1-V3) in the AZ/BNT cohort and 0.49 nmol/L, 0.44 nmol/L, 0.47 nmol/L for BNT/BNT, respectively. Change of median hsTnT and MR-proADM between visits did not show significant increases. One HCW experienced a permanent and three a transient hsTnT increase ≥14 ng/L.ConclusionNo overall subtle, persistent cardiovascular involvement was observed after the 2nd COVID-19 vaccination. Elevated cardiovascular biomarkers in clinically asymptomatic individuals need further investigations.

Kaposi Sarcoma as a Possible Cutaneous Adverse Effect of ChAdOx1 nCov-19 Vaccine: A Case Report

The COVID-19 pandemic prompted the rapid development of vaccines, including the ChAdOx1 nCov-19 (AstraZeneca) vaccine. While effective, adverse effects have been reported, including cutaneous manifestations. Kaposi sarcoma (KS), a vascular tumor linked to Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV-8), has seen increased detection during the pandemic. This study reports a case of classic cutaneous KS in a 79-year-old male following the first dose of the ChAdOx1 nCov-19 vaccine, without prior SARS-CoV-2 infection. The patient developed multiple reddish-blue papules on his legs and feet, confirmed as KS through histopathology. Treatment included radiotherapy and sequential chemotherapy with Doxorubicin. The potential reactivation of latent HHV-8 by the vaccine is explored through mechanisms involving the SARS-CoV-2 spike protein and adenovirus vector, which may induce immune responses and inflammatory pathways. Although establishing a direct causal link remains challenging, the case highlights the need for vigilance regarding KS reactivation post-vaccination. Further large-scale studies are warranted to elucidate the relationship between COVID-19 vaccines and latent virus reactivation, ensuring comprehensive safety assessments and informed public health decisions.

Risk for Facial Palsy after COVID-19 Vaccination, South Korea, 2021-2022.

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

Subsequent Vaccination against SARS-CoV-2 after Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe complication following vaccination with adenovirus vector-based COVID-19 vaccines. Antibodies directed against platelet factor 4 (PF4) are thought to be responsible for platelet activation and subsequent thromboembolic events in these patients. Since a single vaccination does not lead to sufficient immunization, subsequent vaccinations against COVID-19 have been recommended. However, concerns exist regarding the possible development of a new thromboembolic episode after subsequent vaccinations in VITT patients. Methods: We prospectively analyzed follow-up data from four VITT patients (three women and one man; median age, 44 years [range, 22 to 62 years]) who subsequently received additional COVID-19 vaccines. Platelet counts, anti-PF4/heparin antibody level measurements, and a functional platelet activation assay were performed at each follow-up visit. Additionally, we conducted a literature review and summarized similar reports on the outcome of subsequent vaccinations in patients with VITT. Results: The patients had developed thrombocytopenia and thrombosis 4 to 17 days after the first vaccination with ChAdOx1 nCoV-19. The optical densities (ODs) of anti-PF4/heparin antibodies decreased with time, and three out of four patients tested negative within 4 months. One patient remained positive even after 10 months post first vaccination. All four patients received an mRNA-based vaccine as a second vaccination against SARS-CoV-2. No significant drop in platelet count or new thromboembolic complications were observed during follow-up. We identified seven publications reporting subsequent COVID-19 vaccination in VITT patients. None of the patients developed thrombocytopenia or thrombosis after the subsequent vaccination. Conclusion: Subsequent vaccination with an mRNA vaccine appears to be safe in VITT patients.

Influence of previous COVID-19 exposure and vaccine type (CoronaVac, ChAdOx1 nCov-19 or BNT162b2) on antibody and cytokine (Th1 or Th2) responses

ABSTRACT To achieve global herd immunity, widespread vaccination is the most effective strategy. Vaccines stimulate the immune system, generating cytokines and chemokines, isotype antibodies, and neutralizing antibodies; all these molecules collectively provide a more comprehensive characterization of the immune response post-vaccination. We conducted a longitudinal study in northwestern Mexico, involving 120 individuals before vaccination and after the first dose of the SARS-CoV-2 vaccine, and 46 individuals after their second dose. Our findings reveal that antibody levels stabilize over time; cytokine levels generally increase following the first dose but decrease after the second dose and higher than normal levels in IgG1 and IgG3 concentrations are present. Most of the innate cytokines determined in this study were higher after the first dose of the vaccine. Regardless of previous infection history, this finding suggests that the first dose of the vaccine is crucial and may stimulate immunity by enhancing the innate immune response. Conversely, increased levels of IL-4, indicative of a Th2 response, were found in individuals without prior exposure to the virus and in those vaccinated with CoronaVac. These results suggest that the immune response to COVID-19 vaccines is multi-faceted, with preexisting immunity potentiating a more robust innate response. Vaccine type plays a critical role, with genetic vaccines favoring a Th1 response and inactivated vaccines like CoronaVac skewing toward a Th2 profile.

Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-Cell Vaccine.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses, which are delivered by replication-deficient vector ChAdOx1. It directs T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the β-coronavirus family.

Long-Term Safety and Immunogenicity of AZD1222 (ChAdOx1 nCoV-19): 2-Year Follow-Up from a Phase 3 Study.

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity. After 2 years, no emergent safety signals were observed for AZD1222, and no cases of thrombotic thrombocytopenia syndrome were reported. The assessment of anti-SARS-CoV-2 nucleocapsid antibody titers confirmed the durability of AZD1222 efficacy for up to 6 months, after which infection rates in the AZD1222 group increased over time. Despite this, all-cause and COVID-19-related mortality remained low through the study end, potentially reflecting the post-Omicron decoupling of SARS-CoV-2 infection rates and severe COVID-19 outcomes. Geometric mean titers were elevated for anti-SARS-CoV-2 neutralizing antibodies at the 1-year study visit and the anti-spike antibodies were elevated at year 2, providing further evidence of increasing SARS-CoV-2 infections over long-term follow-up. Overall, this 2-year follow-up of the AZD1222 phase 3 study confirms that the long-term safety profile remains consistent with previous findings and supports the continued need for COVID-19 booster vaccinations due to waning efficacy and humoral immunity.

Alterations of plasma metabolomes and their correlations with immunogenicity in maintenance hemodialysis patients receiving different COVID-19 vaccine regimens.

Maintenance hemodialysis (MHD) patients exhibit compromised immune responses, leading to lower immunogenicity to the COVID-19 vaccine than the general population. The metabolomic factors influencing COVID-19 vaccine response in MHD patients remain elusive. A cross-sectional study was conducted with 30 MHD patients, divided into three vaccine regimen groups (N= 10 per group): homologous CoronaVac® (SV-SV), homologous ChAdOx1 nCoV-19 (AZ-AZ), and heterologous prime-boost (SV-AZ). Plasma samples were collected at baseline and at 28 days after the final dose to analyze 92 metabolomic levels using targeted metabolomics. The study included 30 MHD patients (mean age 56.67 ± 10.79 years) with similar neutralizing antibody (nAb) levels across vaccine regimens. The most significant differences in metabolomics were found between AZ-AZ and SV-SV, followed by SV-AZ versus SV-SV, and AZ-AZ versus SV-AZ. Overall, the metabolomic changes involved amino acids like glutamate and phenylalanine, and phospholipids. Prevaccination metabolomic profiles, including PG (38:1), lysoPE (20:2), lysoPC (18:2), lysoPI (18:1), and PC (34:2), exhibited negative correlations with postvaccination nAb levels. Different COVID-19 vaccine regimens had unique interactions with the immune response in MHD patients. Amino acid and phospholipid metabolisms play crucial roles in nAb formation, with the phospholipid metabolism being a potentially predictive marker of vaccine immunogenicity among MHD patients.

A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications

Adenoviruses (Ad) have demonstrated significant success as replication-deficient (RD) viral vectored vaccines, as well as broad potential across gene therapy and cancer therapy. Ad vectors transduce human cells via direct interactions between the viral fiber knob and cell surface receptors, with secondary cellular integrin interactions. Ad receptor usage is diverse across the extensive phylogeny. Commonly studied human Ad serotype 5 (Ad5), and chimpanzee Ad-derived vector “ChAdOx1” in licensed ChAdOx1 nCoV-19 vaccine, both form primary interactions with the Coxsackie and Adenovirus Receptor (CAR), which is expressed on human epithelial cells and erythrocytes. CAR usage is suboptimal for targeted gene delivery to cells with low/negative CAR expression, including human dendritic cells (DCs) and vascular smooth muscle cells (VSMCs). We evaluated the performance of a RD Ad5 vector pseudotyped with the fiber knob of human Ad serotype 49, termed Ad5/49K vector. Ad5/49K demonstrated superior transduction of murine and human DCs over Ad5, which translated into significantly increased T cell immunogenicity when evaluated in a mouse cancer vaccine model using 5T4 tumour-associated antigen. Additionally, Ad5/49K exhibited enhanced transduction of primary human VSMCs. These data highlight the potential of Ad5/49K vector for both vascular gene therapy applications and as a potent vaccine vector.

Ounis Syndrome with Syncope, Yasser’s Hypocalcemic Sign, and Possible Pulmonary Embolism after AstraZeneca ChAdOx1 nCoV-19 Vaccine in Elderly; Risk and Management

ounis Syndrome with Syncope, Yasser’s Hypocalcemic Sign, and Possible Pulmonary Embolism after AstraZeneca ChAdOx1 nCoV-19 Vaccine in Elderly; Risk and Management

Validation of the newly proposed Brighton Collaboration case definition for vaccine-induced immune thrombocytopenia and thrombosis

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a newly recognized syndrome mediated by anti-platelet factor 4 antibodies induced by Covid-19 adenovirus-vectored vaccines including ChAdOx1 nCoV-19 and Ad26.COV2.S. This study validated a proposed Brighton Collaboration case definition for VITT. A data collection form was developed and used to capture the variations in VITT criteria and assess their level of diagnostic certainty from adjudicated positive VITT case datasheets in Germany (n = 71), UK (n = 220), Australia (n = 203), and Taiwan (n = 56). We observed high prevalence of each component of the proposed VITT definition in positive cases (84%–100%), except for the occurrence of thrombosis or thromboembolism criterion in only 34% of VITT cases in Taiwan. The sensitivity of this proposed definition was 100% for Germany and UK, 92% for Australia, and 89% for Taiwan cases. These findings support the validity of this case definition for VITT.

Monitoring of adaptive immune responses in healthcare workers who received a Coronavirus disease 2019 vaccine booster dose.

Coronavirus disease 2019 (COVID-19) has become a global pandemic and led to increased mortality and morbidity. Vaccines against the etiologic agent; severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were approved for emergency use on different platforms. In the early phase of the pandemic, Thai healthcare workers (HCWs) received CoronaVac, an inactivated vaccine, as the first vaccine against SARS-CoV-2, followed by ChAdOx1 nCoV-19, a viral vector-based vaccine, or BNT162b2, an mRNA vaccine, as a booster dose. This preliminary study evaluated the immunogenicity of ChAdOx1 nCoV-19 and BNT162b2 as a booster dose in HCWs who previously received two doses of CoronaVac. Ten HCW participants received ChAdOx1 nCoV-19 and another 10 HCWs received BNT162b2 as a booster dose after two doses of CoronaVac. Anti-RBD IgG, neutralizing antibodies (NAb), and cellular immunity, including interferon-gamma (IFN-γ)-releasing CD4, CD8, double negative T cells, and NK cells, were measured at 3 and 5 months after the booster dose. There was no significant difference in anti-RBD IgG levels at 3 and 5 months between the two different types of booster vaccine. The levels of anti-RBD IgG and NAb were significantly decreased at 5 months. HCWs receiving BNT162b2 had significantly higher NAb levels than those receiving ChAdOx1 nCoV-19 at 5 months after the booster dose. IFN-γ release from CD4 T cells was detected at 3 months with no significant difference between the two types of booster vaccines. However, IFN-γ-releasing CD4 T cells were present at 5 months in the ChAdOx1 nCoV-19 group only. ChAdOx1 nCoV-19 or BNT162b2 can be used as a booster dose after completion of the primary series primed by inactivated vaccine. Although the levels of immunity decline at 5 months, they may be adequate during the first 3 months after the booster dose.

Vaccine-induced Thrombotic Thrombocytopenia and Graft Thrombosis in a Renal Transplant Recipient

Abstract The use of COVID-19 vaccines has been associated with sporadic reports of thrombosis with thrombocytopenia, a complication referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Early recognition of this entity before the occurrence of thrombosis detected by imaging is termed as a pre-VITT syndrome. Thrombosis has been reported to occur in the cerebral venous system, splanchnic veins as well as arteries to the lower limbs. We present the case of a young renal transplant recipient who presented with VITT following ChAdOx1 nCoV-19 (Covishield) vaccination; in this case, thrombosis occurred in the intrarenal arteries of the graft kidney.

Calcifediol boosts efficacy of ChAdOx1 nCoV-19 vaccine by upregulating genes promoting memory T cell responses

The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were supplemented with calcifediol, a direct precursor to the biologically active form of vitamin D, calcitriol with an objective to enhance the immunogenicity of the COVISHIELD vaccine. Herein we investigated the effects of calcifediol supplementation on gene expression profiles in individuals who received the COVISHIELD vaccine. Peripheral blood mononuclear cells were isolated from vaccinated individuals with and without calcifediol supplementation at baseline, 3rd and 6th month, and the gene expression profiles were analyzed using high-throughput sequencing. The results revealed distinct patterns of gene expression associated with calcifediol supplementation, suggesting potential molecular mechanisms underlying the beneficial effects of calcifediol in improving the efficacy of COVISHIELD vaccine via augmentation of T cell activation, proliferation and T cell memory responses. Additionally, there was upregulation of NOD like receptor, JAK/STAT and TGF beta signaling pathways. Calcifediol supplementation in vaccinated individuals also downregulated the pathways related to the Coronavirus disease. Taken together, our findings provide valuable insights into the interplay between vitamin D receptor (VDR) signaling and vaccine-induced immune responses and offer another approach in improving vaccination induced antiviral responses.

Vaccine Adverse Effects Following Covishield among Health-care Workers in Central India

Abstract Introduction: This study aims to analyze common adverse effects following immunization that are temporally associated after receiving the above 2 doses of ChAdOx1 nCoV-19 Vaccine (Covishield) COVID-19 vaccines among health-care worker from January 2021 to April 2021, in the central region of India in a tertiary care hospital. Materials and Methods: A surveillance-based study was conducted between January 2021 and April 2021 among the health-care worker of the tertiary care hospital in the central part of India. The study was designed to identify the adverse effects reported after receiving a ChAdOx1 nCoV-19 Vaccine (Covishield) COVID-19 vaccination and demographic details were collected. Results: Within 48 h of the initial immunization dose, 651 mild adverse effects in all participants were documented. Headache (n = 168, 16%), fever (n = 105, 10%), fatigue (n = 115, 11%), and muscular discomfort (n = 115, 10%) were among the frequent side effects. One hundred and five minor adverse effects were reported between 3 and 7 days. No major adverse effects were observed after the first and second doses of vaccine. Conclusion: The first 48 h were the most common observational period for the short-term adverse effects of both dosages. After 15 days of both doses, the incidence declined for consecutive weeks until it was completely absent. The symptoms were transient and of a minor in nature. There were no documented severe vaccine-related side effects. Our research demonstrated that the vaccination had a decreased adverse event profile, was safe, and was well-tolerated.

Immunogenicity and safety of beta variant COVID-19 vaccine AZD2816 and AZD1222 (ChAdOx1 nCoV-19) as primary-series vaccination for previously unvaccinated adults in Brazil, South Africa, Poland, and the UK: a randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study

AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated. In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed. Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2. Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants. AstraZeneca.

Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines

Vaccination has proven to be a valuable tool to combat SARS-CoV-2. However, reports of rare adverse reactions such as thrombosis/thrombocytopenia syndrome after ChAdOx1 nCoV-19 vaccination have caused scientific, public and media concern. ChAdOx1 was vectorised from the Y25 chimpanzee adenovirus, which was selected due to low human seroprevalence to circumvent pre-existing immunity. In this study, we aimed to explore patterns of T-cell activation after SARS-CoV-2 COVID-19 vaccine exposure in vitro using PBMCs collected from pre-pandemic ChAdOx1 nCoV-19 naïve healthy donors (HDs), and ChAdOx1 nCoV-19 and Pfizer vaccinated controls. PBMCs were assessed for T-cell proliferation using the lymphocyte transformation test (LTT) following exposure to SARS-CoV-2 COVID-19 vaccines. Cytokine analysis was performed via intracellular cytokine staining, ELISpot assay and LEGENDplex immunoassays. T-cell assays performed in pre-pandemic vaccine naïve HDs, revealed widespread lymphocyte stimulation after exposure to ChAdOx1 nCoV-19 (95%), ChAdOx-spike (90%) and the Ad26.COV2. S vaccine, but not on exposure to the BNT162b2 vaccine. ICS analysis demonstrated that CD4+ CD45RO+ memory T-cells are activated by ChAdOx1 nCoV-19 in vaccine naïve HDs. Cytometric immunoassays showed ChAdOx1 nCoV-19 exposure was associated with the release of proinflammatory and cytotoxic molecules, such as IFN-γ, IL-6, perforin, granzyme B and FasL. These studies demonstrate a ubiquitous T-cell response to ChAdOx1 nCoV-19 and Ad26.COV2. S in HDs recruited prior to the SARS-CoV-2 pandemic, with T-cell stimulation also identified in vaccinated controls. This may be due to underlying T-cell cross-reactivity with prevalent human adenoviruses and further study will be needed to identify T-cell epitopes involved.

Immunological Insights: A Multicenter Longitudinal Study on Humoral Response to COVID-19 Vaccines in Greece

Vaccination has emerged as the most effective tool in the battle against COVID-19. To optimize vaccination protocols, a deeper understanding of the immune response to vaccination, including influential factors and its duration, is essential. This study aimed to assess the humoral response in vaccinated individuals with or without prior SARS-CoV-2 infection. A prospective observational study was conducted across 14 private healthcare structures in Greece. Anti-spike IgG titers were measured at different timepoints following the initial vaccination and booster doses of the BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. A total of 505 participants were included in the first phase, evaluating the humoral response after the initial vaccination, and 311 participants were involved in the second phase, assessing the effects of booster vaccination. All vaccines elicited high anti-S IgG titers initially, followed by a subsequent decline that was addressed by the booster vaccination. The humoral response was sustained up to one year after the booster vaccination. mRNA vaccines induced higher anti-S IgG titers compared to vector vaccines, with mRNA-1273 eliciting higher titers than BNT162b2. Vaccination resulted in higher antibody titers than natural infection alone; however, convalescent patients who received vaccination had significantly higher anti-S IgG titers compared to those who received the booster vaccine without previous SARS-CoV-2 infection. Lower antibody titers were observed in men and older patients (>51.5 years old), as well as smokers, although the decline rate was lower in these subgroups. These results underscore the importance of booster doses and reveal the potential influence of age, gender, smoking habits, and vaccine type on varying humoral responses. Long-term monitoring of antibody persistence, evaluation of cellular immune responses, and assessment of vaccine efficacy against emerging variants should be considered to enhance our understanding of immunity dynamics and inform vaccine development and deployment strategies.

RBD mutations at the residues K417, E484, N501 reduced immunoreactivity with antisera from vaccinated and COVID-19 recovered patients.

It is unclear whether induced spike protein-specific antibodies due to infections with SARS-CoV-2 or to the prototypic Wuhan isolate-based vaccination can immune-react with the emerging variants of SARS-CoV-2. The main objective of the study was to measure the immunoreactivity of induced antibodies postvaccination with Covishield™ (ChAdOx1 nCoV-19 coronavirus vaccines) or infections with SARS-CoV-2 by using selected peptides of the spike protein of wild type and variants of SARS-CoV-2. Thirty patients who had recovered from SARS-CoV-2 infections and 30 individuals vaccinated with both doses of Covishield™ were recruited for the study. Venous blood samples (5 mL) were collected at a single time point from patients within 3-4 weeks of recovery from SARS-CoV-2 infections or receiving both doses of Covishield™ vaccines. The serum levels of total immunoglobulin were measured in both study groups. A total of 12 peptides of 10 to 24 amino acids length spanning to the receptor-binding domain (RBD) of wild type of SARS-CoV-2 and their variants were synthesized. The serum levels of immune-reactive antibodies were measured using these peptides. The serum levels of total antibodies were found to be significantly (p<0.001) higher in the vaccinated individuals as compared to COVID-19 recovered patients. Our study reported that the mutations in the RBD at the residues K417, E484, and N501 have been associated with reduced immunoreactivity with anti-sera of vaccinated people and COVID-19 recovered patients. The amino acid substitutions at the RBD of SARS-CoV-2 have been associated with a higher potential to escape the humoral immune response.