Sensitizing breast cancers to immune checkpoint inhibitors through CD27 agonism and vaccination against tumor-associated antigen

Project objective: Despite the recent revolution in immune checkpoint inhibitors (ICIs), only modest improvement in overall survival and likely caused by not enough potent cellular immunity among BC patients. Our lab has been focus on inducing cellular immunity against HER2+ BC through vaccination against the tumor-associated antigen HER2. Approximately 20 years ago, we performed an experimental pilot study by administrating HER2 peptide and recombinant protein pulsed dendritic cells (DC vaccine) to six patients with refractory HER2+ advanced or metastatic (stage II (>= 6 +LN), III, or stage IV) BC. We followed the patients on 2019 found that all of the six patients were still alive, 18 years after vaccination. Their blood sample were analyzed with cytometry by time-offlight (CyTOF) and found there is a significantly increased presence of CD27 expressing memory T cells in response to HER2 peptide stimulation. Recent report on the SARS-CoV2 mRNA vaccine also suggested that CD27 expressing memory T cells plays a critical role in long-lasting cellular immunity against SARS-CoV2 infection. Therefore, we hypothesized that CD27 plays a critical role in cellular immunity against BC, and the stimulation of CD27 expressing T cells with mAb targeting CD27 significantly increase the cellular immunity triggered by vaccination against tumor-associated antigen. Result(s): We recapitulate the rise of CD27+ antigen specific T cells among the vaccinated patients using a transgenic mouse model expressing human CD27. When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination. Using an ICIinsensitive syngeneic HER2+ BC models, we found 50% of mice in the combination group of aCD27 antibody plus Ad-HER2 showed total tumor regression by the end of study. When combined with anti-PD1 antibody, the combination of AdHER2 and Varlilumab leads to total tumor regression in 90% of tumor bearing mice with syngeneic HER2+ BC, indicating that the vaccination against tumor associated antigen HER2 plus anti-CD27 antibody sensitized ICI-insensitive HER2+ BC toward ICI. Conclusion(s): Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.

Adenovirus vector and mRNA vaccines: Mechanisms regulating their immunogenicity.

Replication-incompetent adenovirus (Ad) vector and mRNA-lipid nanoparticle (LNP) constructs represent two modular vaccine platforms that have attracted substantial interest over the past two decades. Due to the COVID-19 pandemic and the rapid development of multiple successful vaccines based on these technologies, there is now clear real-world evidence of the utility and efficacy of these platforms. Considerable optimization and refinement efforts underpin the successful application of these technologies. Despite this, our understanding of the specific pathways and processes engaged by these vaccines to stimulate the immune response remains incomplete. This review will synthesize our current knowledge of the specific mechanisms by which CD8+ T cell and antibody responses are induced by each of these vaccine platforms, and how this can be impacted by specific vaccine construction techniques. Key gaps in our knowledge are also highlighted, which can hopefully focus future studies.

Updated Guidance Regarding The Risk ofAllergic Reactions to COVID-19 Vaccines and Recommended Evaluation and Management: A GRADE Assessment, and International Consensus Approach.

This guidance updates 2021 GRADE recomendations regarding immediate allergic reactions following COVID-19 vaccines and addresses re-vaccinating individuals with 1st dose allergic reactions and allergy testing to determine re-vaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 re-vaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommenations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the UK, and the US formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy, and re-vaccination after a prior immediate allergic reaction. We suggest against >15-minute post-vaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest re-vaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise, in a properly equipped setting. We suggest against pre-medication, split-dosing, or special precautions because of a comorbid allergic history.

Adenovirus vector vaccines

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirus（Ad） vector vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019（COVID-19）, worldwide.Alternate :抄録非増殖型アデノウイルスベクターは、in vivoへの直接投与において優れた遺伝子導入活性を示すことから、病原体由来の抗原タンパク質を発現させることにより、新興・再興感染症に対するワクチンベクターとして積極的な開発が進められてきた。最近では、新型コロナウイルス感染症（COVID-19）に対するワクチンとして、欧米中露において迅速な実用化がなされた。本稿では、アデノウイルスベクターの特性、COVID-19に対するアデノウイルスベクターワクチンの特徴、およびアデノウイルスベクターワクチンの可能性について解説する。

Heterologous chimpanzee adenovirus vector immunizations for SARS-CoV-2 spike and nucleocapsid protect hamsters against COVID-19.

Available COVID-19 vaccine only provide protection for a limited time due in part to the rapid emergence of viral variants with spike protein mutations, necessitating the generation of new vaccines to combat SARS-CoV-2. Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing early SARS-CoV-2 isolate spike (S) or nucleocapsid (N) proteins, the latter expressed as a fusion protein within herpes simplex virus glycoprotein D (gD), were tested individually or as a mixture in a hamster COVID-19 SARS-CoV-2 challenge model. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gD N fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable than the S protein may potentiate and prolong protection achieved by the currently used S protein based genetic COVID-19 vaccines.

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.

Safety of Covid-19 vaccination in patients with mastocytosis

Background: Mastocytosis is a disorder characterized by an accumulation of mast cells in one or more organ systems and increased risk for severe anaphylaxis. Coronavirus disease 2019 (COVID-19) is associated with a relatively high rate of severe lung disease and mortality. During 2020, vaccines against COVID-19 were developed. The reported frequency of severe side effects appears to be low even in patients with severe allergies and mastocytosis. The aim of this study was to evaluate the safety of vaccines against COVID-19 in patients with mastocytosis. Method(s): Retrospective analysis of patients with a diagnosis of mastocytosis who have been vaccinated against COVID-19 in our department, from January to December 2021. Demographic data, history of anaphylactic reactions, COVID-19 vaccines used, premedication with antihistamines and hypersensitivity reactions were reviewed. Result(s): This study included 14 patients (64% (n = 9) were female, median age 51 +/- 18 years). Twelve (86%) patients had indolent systemic mastocytosis and two (14%) had cutaneous mastocytosis. Four (29%) patients had a history of idiopathic anaphylaxis, three (21%) reported anaphylaxis to hymenoptera venoms and one (7%) anaphylaxis to NSAID. The median basal serum tryptase level was 38.9 ng/ml, with a range from 12.7 to 91 ng/ml. Thirteen (93%) patients received an mRNA vaccine, and one adenoviral vector vaccine (7%), 2 doses each (28 administrations in total). None of the patients received premedication with antihistamines before the vaccination. None of the patients presented hypersensitivity reactions after the vaccine against COVID-19. Conclusion(s): As reported in recent studies, vaccination against COVID-19 in adult patients with mastocytosis is safe. Some authors recommend premedication in patients with mastocytosis at high risk for anaphylaxis. In our study, none of the patients received premedication and no hypersensitivity reactions were observed. More studies are needed, but in our sample, as observed for other vaccines, the vaccine against COVID-19 in patients with mastocytosis was safe.

Pre-existing humoral immunity and CD4+ T cell response correlate with cross-reactivity against SARS-CoV-2 Omicron subvariants after heterologous prime-boost vaccination.

BACKGROUND: Information regarding the heterologous prime-boost COVID vaccination has been fully elucidated. The study aimed to evaluate both humoral, cellular immunity and cross-reactivity against variants after heterologous vaccination. METHODS: We recruited healthcare workers previously primed with Oxford/AstraZeneca ChAdOx1-S vaccines and boosted with Moderna mRNA-1273 vaccine boost to evaluate the immunological response. Assay used: anti-spike RBD antibody, surrogate virus neutralizing antibody and interferon-γ release assay. RESULTS: All participants exhibited higher humoral and cellular immune response after the booster regardless of prior antibody level, but those with higher antibody level demonstrated stronger booster response, especially against omicron BA.1 and BA.2 variants. The pre-booster IFN-γ release by CD4+ T cells correlates with post-booster neutralizing antibody against BA.1 and BA.2 variant after adjustment with age and gender. CONCLUSIONS: A heterologous mRNA boost is highly immunogenic. The pre-existing neutralizing antibody level and CD4+ T cells response correlates with post-booster neutralization reactivity against the Omicron variant.

Persistence of immune response in heterologous COVID vaccination schedules in the Com-COV2 study - A single-blind, randomised trial incorporating mRNA, viral-vector and protein-adjuvant vaccines.

BACKGROUND: Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development. METHODS: Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose 'ChAd' (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or 'BNT' (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8-12 weeks later with either the homologous vaccine, or 'Mod' (mRNA-1273, Spikevax, Moderna) or 'NVX' (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration. FINDINGS: In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N = 540, 45% female) or BNT (N = 532, 39% female) as part of the national vaccination programme. In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95% CI (confidence interval): 8.2, 11.5) at D28 to 6.2 (95% CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95% CI:2.5,3.5) to 2.4 (95% CI:1.9, 3.0). In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The adjusted GMR (aGMR) for BNT/Mod compared with BNT/BNT increased from 1.36 (95% CI: 1.17, 1.58) at D28 to 1.52 (95% CI: 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95% CI: 0.47, 0.64) at day 28 and 0.62 (95% CI: 0.49, 0.78) at day 196. Heterologous ChAd-primed schedules produced and maintained the largest T-cell responses until D196. Immunisation with BNT/NVX generated a qualitatively different antibody response to BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels of neutralising antibodies. INTERPRETATION: Heterologous ChAd-primed schedules remain more immunogenic over time in comparison to ChAd/ChAd. BNT-primed schedules with a second dose of either mRNA vaccine also remain more immunogenic over time in comparison to BNT/NVX. The emerging data on mixed schedules using the novel vaccine platforms deployed in the COVID-19 pandemic, suggest that heterologous priming schedules might be considered as a viable option sooner in future pandemics. ISRCTN: 27841311 EudraCT:2021-001275-16.

Development and Characterization of a Vector System Based on the Simian Adenovirus Type 25

Technological versatility and the humoral and cellular immune response induction capacity have conditioned wide spread of adenoviral vectors as vaccine and gene therapy drugs. However, vaccination with Sputnik V made a significant portion of the population immune to the types 5 and 26 (Ad5 and Ad26) recombinant human adenovirus vectors, which are some of the most frequently used bases for candidate vaccines. Today, vaccine designers tend to select alternative adenovirus serotypes as platforms to develop vaccines against new pathogens on. A good example is simian adenovirus type 25 (SAd25), which belongs to subgroup E. It is genetically distant from Ad5 and exhibits extremely low seroprevalence in human beings, which makes it an appealing alternative vaccine vector. The purpose of this work was to design and study a new vaccine platform based on simian adenovirus type 25. We relied on the advanced methods of molecular biology and virology to construct and make recombinant adenoviruses;the phylogenetic analysis in the context of this study was enabled with bioinformatic methods. The resulting recombinant adenoviral vector can effectively replicate itself in the HEK293 cell line (human embryonic kidney cells). This work substantiates the expediency of further investigation into the SAd25 vector as a platform for development of the prevention vaccines against various infectious diseases.Copyright © 2023 Pirogov Russian National Research Medical University. All rights reserved.

Adenovirus vector vaccines.

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirusAdvector DDS vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019COVID-19, worldwide.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Adenovirus vector vaccines.

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirus(Ad)vector DDS vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019(COVID-19), worldwide.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Adenovirus vector vaccines.

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirus(Ad)vector DDS vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019(COVID-19), worldwide.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Efficacy and safety of vector vaccines for the prevention of new coronavirus infection.

The review article discusses vaccines against SARS-CoV 2 based on adenovirus vectors currently used in the world. The concept of creating vector vaccines is described. The data of clinical studies on the efficacy and safety of registered adenovirus-vector vaccines for the prevention of new coronavirus infection are presented. The frequency of serious adverse events after their use is described in detail. In addition, the clinical efficacy of vector vaccines for changing genotypes of the Covid 19 virus has been determined. The review analyzes literature data on the safety and efficacy of vector vaccines against coronavirus infection. The vector vaccines currently used against the new coronavirus infection are quite safe and effective even in relation to the new genotypes of the SARS-CoV 2 virus.Copyright © 2022 Authors. All rights reserved.

Efficacy and safety of vector vaccines for the prevention of new coronavirus infection.

The review article discusses vaccines against SARS-CoV 2 based on adenovirus vectors currently used in the world. The concept of creating vector vaccines is described. The data of clinical studies on the efficacy and safety of registered adenovirus-vector vaccines for the prevention of new coronavirus infection are presented. The frequency of serious adverse events after their use is described in detail. In addition, the clinical efficacy of vector vaccines for changing genotypes of the Covid 19 virus has been determined. The review analyzes literature data on the safety and efficacy of vector vaccines against coronavirus infection. The vector vaccines currently used against the new coronavirus infection are quite safe and effective even in relation to the new genotypes of the SARS-CoV 2 virus.Copyright © 2022 Authors. All rights reserved.

Efficacy and safety of vector vaccines for the prevention of new coronavirus infection.

The review article discusses vaccines against SARS-CoV 2 based on adenovirus vectors currently used in the world. The concept of creating vector vaccines is described. The data of clinical studies on the efficacy and safety of registered adenovirus-vector vaccines for the prevention of new coronavirus infection are presented. The frequency of serious adverse events after their use is described in detail. In addition, the clinical efficacy of vector vaccines for changing genotypes of the Covid 19 virus has been determined. The review analyzes literature data on the safety and efficacy of vector vaccines against coronavirus infection. The vector vaccines currently used against the new coronavirus infection are quite safe and effective even in relation to the new genotypes of the SARS-CoV 2 virus.Copyright © 2022 Authors. All rights reserved.

Current pandemic COVID-19 vaccine strategies and development: a comprehensive review

The coronavirus disease-19 pandemic with the characteristics of asymptomatic condition, long incubation period and poor treatment has influenced the entire globe. Coronaviruses are important emergent pathogens, specifically, the recently emerged sever acute respiratory syndrome coronavirus 2, the causative virus of the current COVID-19 pandemic. To mitigate the virus and curtail the infection risk, vaccines are the most hopeful solution. The protein structure and genome sequence of SARS-CoV-2 were processed and provided in record time;providing feasibility to the development of COVID-19 vaccines. In an unprecedented scientific and technological effort, vaccines against SARS-CoV-2 have been developed in less than one year. This review addresses the approaches adopted for SARS-CoV-2 vaccine development and the effectiveness of the currently approved vaccines.Copyright © 2023, Finlay Ediciones. All rights reserved.

Developing an assay to distinguish between HIT and VITT antibodies

Introduction Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, but severe side effect after Covid-19 and other vaccinations. First cases of VITT-mimicking antibodies in unvaccinated patients with recurrent thrombosis have been described. Differentiation between heparin-induced thrombocytopenia (HIT) and VITT is difficult in some patients. Widely used enzyme-linked immunoassays (EIA) cannot differentiate between the two, some of them even fail to detect VITT antibodies. So far, differentiation between HIT-like and VITT-like anti-PF4 antibodies can only be performed in specialized laboratories by functional tests using the heparin-induced platelet activation (HIPA) or PF4-induced platelet activation (PIPA) test. We have developed an assay, which can distinguish between HIT and VITT antibodies and can be used in any hospital laboratory. Method Confirming platelet-activation assays (HIPA and PIPA) were performed as described.[1] We defined 3 cohorts: 1) Negative controls (n = 112, including 35 healthy donors from before 2020, 46 clinical patients suspected for HIT but with negative EIA and HIPA and 31 non-thrombotic patients);2) classical HIT-patients with positive EIA and HIPA (n = 121);3) typical VITT patients (n = 63;presenting after vaccination with adenoviral vector-based Covid-19 vaccine and positive EIA and PIPA). Samples were analyzed by an automated coagulation analyzer ACL AcuStar (Werfen / IL Inc., Bedford, MA, USA) using HemosIL AcuStar HIT-IgG(PF4-H) and a prototype of VITT-IgG(PF4) assay according to the manufacturer's protocol. For both assays, raw data was analyzed as relative light units (RLU). Results All VITT samples were positive in the prototype VITT-assay (Fig. 1);only a few (n = 9;14.3 %) also showed weakly positive results in the HIT-assay. On the other hand, most of the HIT samples showed positive results in the HIT-assay (113;93.4 %), 34 of them (30.1 %) also reacted positive in the prototype VITT-assay (12 of them strongly;10.6 %), and three demonstrated an antibody pattern like autoimmune VITT. Negative control samples where all non-reactive in the HITassay and served to adjust the cutoff for the prototype VITT-assay. Conclusion The different reaction pattern of samples of HIT and VITT patients using HemosIL AcuStar HIT-IgG(PF4-H) and a VITT prototype assay was able to distinguish between the two antibody entities for the first time. The combination of assays can facilitate a rapid decision whether heparin may be used for treatment and also identify patients with autoimmune-VITT as a cause of recurrent thrombosis. (Table Presented).

FDG-avid lymph nodes (LN) in response to vaccines for SARS-CoV-2

Aim/Introduction: Vaccines against SARS-CoV-2 virus were developed due to the impetuous coronavirus pandemic. Vaccines hold a possibility to provoke side effects. The aim of our study was to examine the impact of COVID-19 vaccination on the incidence and duration of false-positive FDG-avid lymphadenopathy after vaccination with different types of vaccines and to determine its relationship with age, gender, and vaccine type. Material(s) and Method(s): The retrospective study included 103 patients who met the following criteria:18F-FDG PET/CT scan performed (in the period from August 2021 to December 2021) for staging or restaging of diagnosed oncological diseases at different time periods after vaccination Pfizer-BioNTech, Moderna-BioNTech and Oxford-AstraZeneca. Exclusion criteria were incomplete information about vaccination, patients with a diagnosed malignant lymphoproliferative disease, concomitant benign pathology of the lymphatic system, history of acute viral infection up to 3 months from the date of PET/CT. Result(s): False-positive reactive lymphadenopathy was identified in 35 (34%) of 103 patients included in our study cohort, which occurred during the first 2 weeks to 12 weeks after vaccination and manifested as increased metabolic activity in regional non-enlarged lymph nodes: ipsilateral axillary lymph nodes of levels I-III, as well as cervical LN of levels IV and VB). A significant moderate decline in metabolic activity in the LN over time was reported, as well as a decrease in the detection rate of PET-positive reactive findings with time. The results showed a trend of a positive relationship - the occurrence of reactive lymphadenopathy more often in women than in men. The detection rate, as well as the intensity of the activity of glucose metabolism, were higher in patients under the age of 50 compared to those >= 50 years. However, we did not find significant differences between the studied types of vaccines (p >0.05). Conclusion(s): Multidisciplinary physician awareness is essential regarding the possibility of false-positive FDG lymphadenopathy in relation to local inflammation and as a manifestation of the immune response due to COVID-19 RNA vaccination and adenoviral vector-based vaccine up to 12 weeks after injection, in order to optimize the clinical interpretation of hybrid scan results that determine the subsequent therapeutic approach of cancer patients. The results of the present study demonstrate the importance of vaccination on the contralateral side of the tumor drainage, as well as taking a thorough anamnesis. Keywords: FDG PET/CT, false positive lymphadenopathy, vaccination.

Serological response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 prime-boost vaccination with a twelve-week interval.

The appropriate interval between heterologous prime adenoviral vectored vaccination and boost mRNA vaccination remains unclear. We recruited 100 adult participants to receive a prime adenoviral vectored vaccine (ChAdOx1, AstraZeneca) and a boost mRNA vaccine (mRNA-1273, Moderna) 12 weeks apart and checked their serum SARS-CoV-2 anti-spike IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on the 28th day after the boost dose. Results were compared with our previous study cohorts who received the same prime-boost vaccinations at 4- and 8-week intervals. Compared to other heterologous vaccination groups, the 12-week interval group had higher neutralizing antibody titers against SARS-CoV-2 variants than the 4-week interval group and was similar to the 8-week interval group at day 28. Adverse reactions after the boost dose were mild and transient. Our results support deploying viral vectored and mRNA vaccines in a flexible schedule with intervals from 8 to 12 weeks.