Certolizumab

Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.

Experiences of adult epilepsy patients with COVID-19 infections and vaccinations

Objective: To assess the course of COVID-19 infections and the tolerability of the mRNA vaccines of Moderna and Pfizer/BioNTech and the viral vector vaccines from Astra Zeneca and Johnson & Johnson in adult patients with epilepsy (PWE). Method(s): From July 2020 to July 2021, we consecutively included adult outpatients with confirmed epilepsy. These PWE were interviewed about COVID-19 infections and vaccinations. Results of follow-up visits were added until the cut-off date (December 31, 2021). The data of COVID-19-infected without vaccinations or fully vaccinated PWE without COVID-19 infections were analyzed. Full vaccination was defined as a double vaccination with the Pfizer/BionTech, Moderna, or Astra Zeneca vaccines or a single Johnson & Johnson vaccination. Result(s): At cut-off, 612 of 1152 PWE fulfilled the inclusion criteria: 51 PWE had been infected without vaccination and 561 had full vaccination without infection. Among the infected PWE, 76.5% presented with symptoms;9.8% had a severe course (one death). The leading symptoms were influenza-like disorders (48.7% of infected PWE with symptoms), anosmia (28.2%), and ageusia (20.5%). Seizure increases or relapses after sustained seizure freedom occurred in 7.8%. Adverse events (AEs) were reported by 113 vaccinated PWE (20.1% of all vaccinated PWE). The leading AEs were fatigue, fever, and headache. The AE rate per vaccine was 14.0% for Pfizer/BionTech, 32.7% for Moderna, 25.8% for Astra Zeneca, and 46.2% for Johnson & Johnson. Of the AEs, 93.3% lasted <=1 week. Seizure increase or relapse occurred in 1.4% and was significantly less frequent than in the infected group (p= 0.0016). Conclusion(s): The course of COVID-19 infections and the tolerability of the vaccines were similar as in the general population, yet, seizure worsening occurred more often after the infection than after the vaccination.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, part of Springer Nature.

Post-authorization safety surveillance of Ad.26.COV2.S vaccine: Reports to the Vaccine Adverse Event Reporting System and v-safe, February 2021-February 2022.

BACKGROUND: On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system. METHODS: VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated. RESULTS: During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care. CONCLUSION: Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis.

Performing arts as a non-pharmacological intervention for people with dementia and care-partners: a community case study.

Participation in psychosocial enrichment activities, such as music and arts programming, have shown potential to delay or reduce functional decline - without adverse effects that can be associated with pharmaceuticals. The performing-arts programming described in this community case study was inspired by a community music program called B-Sharp Music Wellness, located in Phoenix, Arizona, which involved small groups of musicians who provided symphony performances for people with dementia. Our community programming sought to engage people with dementia and their informal care partner (typically a spouse) in existing performing-arts programs in their local community, providing social hours and season tickets for either symphony, dance (ballet), or non-musical theater performances. This case study describes the program history and design, including outcomes and lessons learned from the program evaluation of the last full season (2018-19) and partial season (2019-20), when the program was halted due to the COVID-19 pandemic. Program outcomes suggest strategies for, and benefits of, design for performing-arts programs as psychosocial interventions in other communities.

Using humor to increase COVID-19 vaccination intention for the unvaccinated: The moderating role of trust in government

Since COVID-19 was declared a global pandemic, scholars and practitioners have put much effort into testing effective advertising strategies for COVID-19 vaccinations. Guided by humor theories, this study aimed to examine (1) the effect of humor on persuading COVID-19 vaccination and (2) the moderating role of trust in government for the unvaccinated population. Across two studies (college students and general adult populations), for lower trust in government individuals, through greater public service advertisement (PSA) processing depth and believability, there was a higher vaccination intention after the humor (non-humor) advertisement. For higher trust in government individuals, there was evidence that the vaccination intention was lowered after the humor (vs. non-humor) message through lowered PSA processing depth and believability. This study expands humor theory into testing COVID-19 vaccination messages while considering an individual psychological factor, trust in the government, that has emerged as an essential determinant to COVID-19 messaging. The contributions to COVID-19 vaccination advertising strategy and advertising to the unvaccinated population, in general, are discussed.

Humoral Immune Response to Sars-Cov-2 Third Vaccine in Patients with Autoimmune Rheumatic Diseases without Seroconversion after the Initial 2-Dose Regimen

Objectives: To evaluate the humoral immune response to the third dose (booster) of vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases who were seronegative after a two-dose regimen. Method(s): Observational study. Patients with autoimmune rheumatic diseases who had not achieved seroconversion after a two-dose vaccine schedule against SARS-CoV-2 were included. To assess the humoral immune response, anti-RBD IgG (S protein receptor binding domain) neutralizing antibody titers were determined by ELISA (cutoff titer 200). The determination was made between 30 to 45 days after the third dose. Result(s): From 66 patients who received SARS-CoV-2 vaccination, 18 patients (29.5%) were seronegative after a two-dose schedule. 61% had SLE, 77% had comorbidities (61% with hypertension, p = 0.03). Patients were on treatment: 10 with prednisone (8 with doses greater than 10 mg/d, p = 0.01), 10 with hydroxychloroquine, one with methotrexate, one with leflunomide, four with azathioprine, five with my cophenolatemofetil and five with rituximab (they are the total number of non-responders on biological treatment, p = 0.03). Regarding the primary vaccination regimen, 11 received BBIBP-CorV (p = 0.01), 5 AZD1222, 1 Gam-COVID-Vac and 1 mRNA1273/Gam-COVID-Vac heterologous scheme. Of these 18 non-responders, 14 received a third dose;nine patients (62%) presented anti-RBD IgG detectable. Of the five patients who did not respond to the booster vaccination, three had received BBIBP-CorV as the initial schedule and the vaccines applied as a third dose were Ad5-nCoV (1), BNT162b2 (1), AZD 1222 (2) and Gam-COVID-Vac (1). They were being treated with: rituximab (2), azathioprine (2) and mycophenolate mofetil (1). Treatment with higher doses of prednisone was the only factor associated with non-seroconversion to the third dose (8 +/- 4.5;p 0.02). Conclusion(s): The third dose of SARS-CoV-2 vaccine allowed to improve the serological response to vaccination, achieving a seroconversion of 62% in this group of patients.

The Relationships among Fear of Covid-19, Health Consciousness, Attitude toward Supplements, and Purchase Intention Using a Moderated Mediation Analysis

The purpose of this study is to examine the relationship between fear of Covid-19 (FoC), attitudes toward supplements (AtS), health consciousness (HC), and purchase intention (PI) by using moderated mediation analysis. The data acquired from 308 customers via faceto-face surveys were analyzed using descriptive statistics and structural equation modeling, and the process model produced by Hayes tested the hypotheses. The results show that the variable of AtA partially mediated the association between FoC and purchase intention. Health consciousness moderates the strength of the relationships between FoC and PI mediated by AtS. According to this, the influence of fear of Covid-19 on purchase intention via the attitudes toward food supplements differs according to consumers' health consciousness (low vs. high). The study provides essential cues for researchers, marketers, and advertisers of food supplements during the COVID-19 pandemic.

Sars-Cov-2 Vaccination Coverage in a Mexican Population with Rheumatic Disease

Objectives: Latest recommendation on SARS-CoV-2 vaccination in patients with systemic rheumatic diseases (SRD) by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) is 3 doses while the Centers for Diseases Control and Prevention (CDC) recommends 5 doses. Method(s): We performed a cross-sectional study from April to November 2022 about SARS-CoV-2 vaccination in an outpatient rheumatology clinic in northeast Mexico. Consecutive SRD patients with a history of COVID-19 vaccination were invited to participate. Patients without SRD were excluded. Eligible participants completed a survey that included demographic data (age, sex, rheumatic disease diagnosis) and SARS-CoV-2 vaccination history (number of doses, and type of vaccine). Result(s): We recruited 252 patients.Vaccine types administered were: BNT162b2 (Pfizer-BioNTech) 55 (23.11%);ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) 130 (54.62%);Ad5-nCoV (CanSinoBIO) 31 (13.03%);Coronavac (Sinovac) 9 (3.78%);mRNA-1273 (Moderna)13 (5.46%). (See Table 1 and Table 2) Conclusion(s): Two thirds of our patients met SARS-CoV-2 vaccination recommendations by ACR and EULAR and 5.95% met CDC criteria. Population without any dose represents 6.74%. SARS-CoV-2 infection in vaccinated patients with SRD is associated with a better outcome compared with unvaccinated. Efforts to increase vaccination coverage need to be done.

Environmental impact assessment for the use of an orally aerosolised adenovirus type-5 vector-based COVID-19 vaccine in randomised clinical trials.

BACKGROUND: An orally aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolised Ad5-nCoV. METHODS: We collected air samples from rooms, swabs from the setting desks of the vaccine nebuliser, mask samples from participants and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type SARS-CoV-2 strain in serum were detected. RESULTS: Only one (4.00%) air samples collected before the initiation of vaccination was positive, which were almost positive during and after the vaccination (97.96%, 100%, respectively). All nurses in the trial A showed at least four-fold increase of the neutralizing antibody against the SARS-CoV-2 after the initiation of the study. In trial B, the positive proportion of the mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7, respectively. CONCLUSION: The vaccination with the orally aerosolised Ad5-nCoV could have some spillage of the vaccine vector viral particles in the environment and cause human exposure.

Aerosol Medication Use in COVID-19 Pandemic

Administration of aerolized drugs to patients diagnosed with COVID-19 leads to the risk of transmission of patient-generated infectious aerosols to healthcare providers.While the COVID-19 pandemic is ongoing, in order to provide the best treatment for patients and at the same time to protect healthcare providers at the highest level, it is necessary to increase access to information and pay maximum attention to preventive measures.Copyright © 2020 Bilimsel Tip Yayinevi. All rights reserved.

Vaccination against COVID-19.

Vaccination is essential to manage the COVID-19 pandemic. Vaccination significantly protects against severe COVID-19, hospitalization and death;it also protects against symptomatic infection and reduces the risk of transmission to other people. Protection against the new SARS-CoV-2 variants may be lower, but protection against severe course and death remains high. Two mRNA vaccines (BNT162b2 and mRNA-1273) and two vector vaccines (AZD1222 and Ad26.COV2.S) are currently available in the Czech Republic. Vaccination of persons over 60 years of age and immunocompromised persons, who are demonstrably at the highest risk of a serious course of the disease, is of the utmost importance. In order to achieve adequate vaccination coverage, it is necessary to motivate other groups of people to be vaccinated, including children over 12 years of age and young adults. Vaccination is also recommended in preg-nant women in the 2nd and 3rd trimesters and in breastfeeding women. For selected groups of vaccines, a third dose of vaccination is recommended (additional third dose 4 weeks after the second dose or a booster dose 8 to 12 months after the second dose). The side effects are usually mild, with serious complications (including anaphylaxis, thrombocytopenia with thrombosis syndrome, myocardi-tis, Guillain-Barre syndrome and capillary leak syndrome) being rare.Copyright © 2021, Trios spol. s.r.o.. All rights reserved.

Guillain-Barré syndrome and COVID-19 vaccines: focus on adenoviral vectors.

COVID-19 vaccination is a life-saving intervention. However, it does not come up without a risk of rare adverse events, which frequency varies between vaccines developed using different technological platforms. The increased risk of Guillain-Barré syndrome (GBS) has been reported for selected adenoviral vector vaccines but not for other vaccine types, including more widely used mRNA preparations. Therefore, it is unlikely that GBS results from the cross-reactivity of antibodies against the SARS-CoV-2 spike protein generated after the COVID-19 vaccination. This paper outlines two hypotheses according to which increased risk of GBS following adenoviral vaccination is due to (1) generation of anti-vector antibodies that may cross-react with proteins involved in biological processes related to myelin and axons, or (2) neuroinvasion of selected adenovirus vectors to the peripheral nervous system, infection of neurons and subsequent inflammation and neuropathies. The rationale behind these hypotheses is outlined, advocating further epidemiological and experimental research to verify them. This is particularly important given the ongoing interest in using adenoviruses in developing vaccines against various infectious diseases and cancer immunotherapeutics.

Recombinant human adenovirus type 5 based vaccine candidates against GIIa- and GIIb-genotype porcine epidemic diarrhea virus induce robust humoral and cellular response in mice.

Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus causing severe watery diarrhea, vomiting, dehydration, and death in piglets. However, most commercial vaccines are developed based on the GI genotype strains, and have poor immune protection against the currently dominant GII genotype strains. Therefore, four novel replication-deficient human adenovirus 5-vectored vaccines expressing codon-optimized forms of the GIIa and GIIb strain spike and S1 glycoproteins were constructed, and their immunogenicity was evaluated in mice by intramuscular (IM) injection. All the recombinant adenoviruses generated robust immune responses, and the immunogenicity of recombinant adenoviruses against the GIIa strain was stronger than that of recombinant adenoviruses against the GIIb strain. Moreover, Ad-XT-tPA-Sopt-vaccinated mice elicited optimal immune effects. In contrast, mice immunized with Ad-XT-tPA-Sopt by oral gavage did not induce strong immune responses. Overall, IM administration of Ad-XT-tPA-Sopt is a promising strategy against PEDV, and this study provides useful information for developing viral vector-based vaccines.

Potential mechanisms of vaccine-induced thrombosis.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome characterized by high-titer anti-platelet factor 4 (PF4) antibodies, thrombocytopenia and arterial and venous thrombosis in unusual sites, as cerebral venous sinuses and splanchnic veins. VITT has been described to occur almost exclusively after administration of ChAdOx1 nCoV-19 and Ad26.COV2.S adenovirus vector- based COVID-19 vaccines. Clinical and laboratory features of VITT resemble those of heparin-induced thrombocytopenia (HIT). It has been hypothesized that negatively charged polyadenylated hexone proteins of the AdV vectors could act as heparin to induce the conformational changes of PF4 molecule that lead to the formation of anti-PF4/polyanion antibodies. The anti-PF4 immune response in VITT is fostered by the presence of a proinflammatory milieu, elicited by some impurities found in ChAdOx1 nCoV-19 vaccine, as well as by soluble spike protein resulting from alternative splice events. Anti-PF4 antibodies bind PF4, forming immune complexes which activate platelets, monocytes and granulocytes, resulting in the VITT's immunothrombosis. The reason why only a tiny minority of patents receiving AdV-based COVID-19 vaccines develop VITT is still unknown. It has been hypothesized that individual intrinsic factors, either acquired (i.e., pre-priming of B cells to produce anti-PF4 antibodies by previous contacts with bacteria or viruses) or inherited (i.e., differences in platelet T-cell ubiquitin ligand-2 [TULA-2] expression) can predispose a few subjects to develop VITT. A better knowledge of the mechanistic basis of VITT is essential to improve the safety and the effectiveness of future vaccines and gene therapies using adenovirus vectors.

An Overview of Adenovirus Vector-based Vaccines against SARS-CoV-2

Adenovirus vectors have been employed to develop a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for curtailing the Covid-19 pandemic spreading. Many different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as an antigen. Spike (S) protein is comprised of S1 and S2 subunits, in which the receptor-binding domain (RBD) of S1 is responsible for recognizing and engaging with its host cellular receptor protein angiotensin-converting enzyme 2 (ACE2), S2 accounts for membrane fusion of virus and host cell. Chimpanzee adenovirus was also used as a vector vaccine for SARS-CoV-2 (ChAdSARS-CoV-2-S) by intramuscular injection, and intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced, with several vaccines receiving Emergency Use Authorization (EUA). It was shown that rhesus macaques were protected from SARS-CoV-2 challenge after a month of being vaccinated with ChAd-SARS-CoV-2-S. A single intranasal or two intramuscular ChAd-SARSCoV-2-S vaccines could induce humoral antibodies and T cell responses to protect the upper and lower respiratory tract against SARS-CoV-2. As the effectiveness was demonstrated in non-human primates, ChAd-SARS-CoV-2-Sa potential option for preventing SARS-CoV-2 infection in humans. However, detecting novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs monitoring. Moreover, the cause of recently documented rare cases of vaccine indicated immune thrombotic thrombocytopenia. This review article provided details for the adenovirus vector vaccine for SARS-CoV-2 in humans and tried to provide solutions to the adenovirus vector hemagglutinin issueCopyright © 2023, World's Veterinary Journal.All Rights Reserved.

On the Influence of Microscopic Mobility in Modelling Pedestrian Communication

In the recent past, wireless network simulations involving pedestrians are getting increasing attention within the research community. Examples are crowd networking, pedestrian communication via Sidelink/D2D, wireless contact tracing to fight the Covid-19 pandemic or the evaluation of Intelligent Transportation Systems (ITS) for the protection of Vulnerable Road Users (VRUs). Since in general the mobile communication depends on the position of the pedestrians, their mobility needs to be modeled. Often simplified mobility models such as the random-waypoint or cellular automata based models are used. However, for ad hoc networks and Inter-Vehicular Communication (IVC), it is well-known that a detailed model for the microscopic mobility has a strong influence – which is why state-of-the-art simulation frameworks for IVC often combine vehicular mobility and network simulators. Therefore, this paper investigates to what extent a detailed modelling of the pedestrian mobility on an operational level influences the results of Pedestrian-to-X Communication (P2X) and its applications. We model P2X scenarios within the open-source coupled simulation environment CrowNet. It enables us to simulate the identical P2X scenario while varying the pedestrian mobility simulator as well as the used model. Two communication scenarios (pedestrian to server via 5G New Radio, pedestrian to pedestrian via PC5 Sidelink) are investigated in different mobility scenarios. Initial results demonstrate that time- and location-dependent factors represented by detailed microscopic mobility models can have a significant influence on the results of wireless communication simulations, indicating a need for more detailed pedestrian mobility models in particular for scenarios with pedestrian crowds. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Realizing supply chain agility under time pressure: Ad hoc supply chains during the COVID‐19 pandemic

When the COVID‐19 pandemic began in 2020, the medical product industry faced an unusual demand shock for personal protective equipment (PPE), including face masks, face shields, disinfectants, and gowns. Companies from various industries responded to the urgent need for these potentially life‐saving products by adopting ad hoc supply chains in an exceptionally short time: They found new suppliers, developed the products, ramped‐up production, and distributed to new customers within weeks or even days. We define these supply chains as ad hoc supply chains that are built for a specific need, an immediate need, and a time‐limited need. By leveraging a unique sampling, we examined how companies realize supply chain agility when building ad hoc supply chains. We develop an emergent theoretical model that proposes dynamic capabilities to enable companies building ad hoc supply chains in response to a specific need, moderated by an entrepreneurial orientation allowing firms to leverage dynamic capabilities at short notice and a temporary orientation that increases a company's focus on exploiting the short‐term opportunity of ad hoc supply chains.

Vaccines for the prevention of infections in adults with haematological malignancies

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and adverse effects of vaccines for the prevention of infections in adults with haematological malignancies.Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Coagulopathies after vaccination against SARS-CoV-2: The sole solution might lead to another problem

The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.

Detection of pre-existing neutralizing antibodies against Ad26 in HIV-1-infected individuals not responding to the Ad26.COV2.S vaccine.

PURPOSE: The Ad26.COV2.S vaccine is a replication-incompetent human adenovirus type 26 vector encoding the SARS-CoV-2 spike protein. In a phase 1-2a trial, a single dose of Ad26.COV2.S induced SARS-CoV-2 spike-specific antibodies in ≥ 96% of healthy adults. To investigate vaccine immunogenicity in HIV-1-infection, we measured SARS-CoV-2 spike-specific antibodies in Ad26.COV2.S vaccinated HIV-1-infected patients and analyzed the presence of pre-existing Ad26 neutralizing antibodies. METHODS: We included all Ad26.COV2.S vaccinated HIV-1-infected patients of Erlangen HIV cohort fulfilling all inclusion criteria. The study cohort consisted of 15 HIV-1-infected patients and three HIV-1-uninfected subjects who received the Ad26.COV2.S vaccine between April and November 2021. Pre-vaccination sera were collected between October 2014 and June 2021, post-vaccination sera between June and December 2021. Neutralizing antibodies towards Ad26 were determined by a FACS-based inhibition assay measuring the expression of SARS-CoV-2 spike and adenoviral proteins in HEK293T cells after in-vitro transduction with Ad26.COV2.S or the control ChAdOx1-S. RESULTS: Six out of 15 HIV-1-infected patients failed to develop SARS-CoV-2-specific antibodies and four patients developed weak antibody responses after vaccination with Ad26.COV2.S. Pre-vaccination sera of four of the six vaccine non-responders showed neutralizing activity towards Ad26.COV2.S but not toward the ChAdOx1-S vaccine at 1:50 dilution. After Ad26.COV2.S vaccination, 17 of the 18 subjects developed strong Ad26-neutralizing activity and only one of the 18 subjects showed neutralizing activity towards the ChAdOx1-S vaccine. CONCLUSION: Ad26.COV2.S vaccination showed a high failure rate in HIV-1-infected patients. Pre-existing immunity against Ad26 could be an important contributor to poor vaccine efficacy in a subgroup of patients.