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Journal of Medical Virology Jul 2022Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2])... (Review)
Review
Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) messenger RNA (mRNA) vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6-month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain immunoglobulin G (IgG) and anti-spike IgG, ranging from 94% to 95% at 90-180 days and 55%-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.
Topics: Antibodies, Viral; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Humans; Immunity, Humoral; Immunoglobulin G; RNA, Messenger; SARS-CoV-2; Vaccination; mRNA Vaccines
PubMed: 35229324
DOI: 10.1002/jmv.27688 -
Frontiers in Immunology 2021The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Two vaccine types were developed using two different...
INTRODUCTION
The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Two vaccine types were developed using two different technologies: viral vectors and mRNA. Thrombosis is one of the most severe and atypical adverse effects of vaccines. This study aimed to analyze published cases of thrombosis after COVID-19 vaccinations to identify patients' features, potential pathophysiological mechanisms, timing of appearance of the adverse events, and other critical issues.
MATERIALS AND METHODS
We performed a systematic electronic search of scientific articles regarding COVID-19 vaccine-related thrombosis and its complications on the PubMed (MEDLINE) database and through manual searches. We selected 10 out of 50 articles from February 1 to May 5, 2021 and performed a descriptive analysis of the adverse events caused by the mRNA-based Pfizer and Moderna vaccines and the adenovirus-based AstraZeneca vaccine.
RESULTS
In the articles on the Pfizer and Moderna vaccines, the sample consisted of three male patients with age heterogeneity. The time from vaccination to admission was ≤3 days in all cases; all patients presented signs of petechiae/purpura at admission, with a low platelet count. In the studies on the AstraZeneca vaccine, the sample consisted of 58 individuals with a high age heterogeneity and a high female prevalence. Symptoms appeared around the ninth day, and headache was the most common symptom. The platelet count was below the lower limit of the normal range. All patients except one were positive for PF4 antibodies. The cerebral venous sinus was the most affected site. Death was the most prevalent outcome in all studies, except for one study in which most of the patients remained alive.
DISCUSSION
Vaccine-induced thrombotic thrombocytopenia (VITT) is an unknown nosological phenomenon secondary to inoculation with the COVID-19 vaccine. Several hypotheses have been formulated regarding its physiopathological mechanism. Recent studies have assumed a mechanism that is assimilable to heparin-induced thrombocytopenia, with protagonist antibodies against the PF4-polyanion complex. Viral DNA has a negative charge and can bind to PF4, causing VITT. New experimental studies have assumed that thrombosis is related to a soluble adenoviral protein spike variant, originating from splicing events, which cause important endothelial inflammatory events, and binding to endothelial cells expressing ACE2.
CONCLUSION
Further studies are needed to better identify VITT's pathophysiological mechanisms and genetic, demographic, or clinical predisposition of high-risk patients, to investigate the correlation of VITT with the different vaccine types, and to test the significance of the findings.
Topics: 2019-nCoV Vaccine mRNA-1273; Antigen-Antibody Complex; BNT162 Vaccine; COVID-19; Cerebral Veins; ChAdOx1 nCoV-19; Female; Headache; Humans; Mass Vaccination; Platelet Factor 4; SARS-CoV-2; Sex Factors; Survival Analysis; Thrombosis
PubMed: 34912330
DOI: 10.3389/fimmu.2021.729251 -
Allergy Jun 2022Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling... (Review)
Review
Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper.
BACKGROUND
Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.
METHODS
MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.
RESULTS
In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.
CONCLUSION
Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.
Topics: Allergens; Anaphylaxis; Animals; Eggs; Food Hypersensitivity; Food Labeling; Humans
PubMed: 34741557
DOI: 10.1111/all.15167 -
Frontiers in Immunology 2021Previous trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia... (Meta-Analysis)
Meta-Analysis
Clinical Benefits and Safety of Gemtuzumab Ozogamicin in Treating Acute Myeloid Leukemia in Various Subgroups: An Updated Systematic Review, Meta-Analysis, and Network Meta-Analysis.
BACKGROUND
Previous trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML.
METHODS
PubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival.
RESULTS
Fifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p < 0.001). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p ≤ 0.023). GO advantages were also associated with nucleophosmin 1 mutations (p ≤ 0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p ≤ 0.03), age of <70 years (p < 0.05), AML (p ≤ 0.017), and CD33(+) (p ≤ 0.021). Both adding GO into induction therapy (p ≤ 0.011) and a lower (<6 mg/m) dose of GO (p ≤ 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (≥6 mg/m) (RR 2.01, p = 0.005), hepatic-related adverse effects (RR 1.29, p = 0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56, p = 0.072).
CONCLUSIONS
These data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO: https://www.crd.york.ac.uk/prospero/], identifier [CRD42020158540].
Topics: Antineoplastic Agents, Immunological; Biomarkers, Tumor; Gemtuzumab; Humans; Karyotype; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Mutation; Prognosis; Sialic Acid Binding Ig-like Lectin 3; Treatment Outcome
PubMed: 34484181
DOI: 10.3389/fimmu.2021.683595 -
PloS One 2021The Mycobacterial heparin-binding hemagglutinin (HBHA) is an important latency-associated antigen that can be used to distinguish between latent tuberculosis infection... (Meta-Analysis)
Meta-Analysis
Mycobacterial heparin-binding hemagglutinin (HBHA)-induced interferon-γ release assay (IGRA) for discrimination of latent and active tuberculosis: A systematic review and meta-analysis.
BACKGROUND
The Mycobacterial heparin-binding hemagglutinin (HBHA) is an important latency-associated antigen that can be used to distinguish between latent tuberculosis infection (LTBI) and active tuberculosis (ATB). Although many studies were explored the efficiency of the HBHA-induced interferon-γ release assay (IGRA) in different populations, the clinical differential value of HBHA-IGRA is still controversial. Therefore, the aim of this study was to determine whether the HBHA-IGRA can be used as an efficient test for the discrimination of LTBI and ATB by a systematic review and meta-analysis.
METHODS
Relevant articles were retrieved from PubMed, Embase, Web of Science, and the Cochrane Library on Oct 18, 2020, with no start date limitation. The quality of each study was evaluated using Review Manager 5.4. The Stata MP v.14.0 software was used to combine sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve, and area under SROC (AUC) to evaluate the diagnostic value of HBHA-IGRA for discrimination of LTBI and ATB. Meta-regression and subgroup analysis were performed for the sources of heterogeneity based on the selection criteria for active TB, the population, the TB burden, the type of antigen, the type of sample, and the time of antigen stimulation.
RESULTS
A total of 13 studies (14 results) were included in this meta-analysis, including 603 ATB patients and 514 LTBI individuals. The pooled sensitivity and specificity of the HBHA-IGRA for discrimination of the LTBI and ATB were 0.70 (95% CI, 0.57~0.80) and 0.78 (95% CI, 0.71~0.84), respectively. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 3.15 (95%CI, 2.43~4.09), 0.39 (95% CI, 0.27~0.56), and 8.11 (95% CI, 4.81~13.67), respectively. The AUC was 0.81 (95% CI, 0.77~0.84). The subgroup analysis showed that the main source of heterogeneity was due to the HIV-infected population incorporated, and the different selection criteria of active TB subjects would also lead to the variation of the pooled sensitivity and specificity. Different TB burdens, HBHA antigen types, sample types, antigen stimulation time and BCG vaccination did not affect the heterogeneity in this analysis.
CONCLUSION
The HBHA-IGRA is a promising immunodiagnostic test for discrimination of latent and active TB, which can be added in commercial IGRAs to enhance the differential diagnostic performance.
Topics: Humans; Interferon-gamma Release Tests; Lectins; Tuberculosis
PubMed: 34270559
DOI: 10.1371/journal.pone.0254571 -
International Journal of Molecular... Jun 2021FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an... (Meta-Analysis)
Meta-Analysis
FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It was registered on the international prospective register of systematic reviews PROSPERO, which helped in identifying articles that met the inclusion criteria. Clinical and preclinical studies involving FcRn and the nasal delivery of biologics were screened, and the risk of bias was assessed across studies using the Oral Health Assessment Tool (OHAT). Among the 12 studies finally included in this systematic review (out of the 758 studies screened), 11 demonstrated efficient transcytosis of biologics through the nasal epithelium. Only three studies evaluated the potential toxicity of biologics' intranasal delivery, and they all showed that it was safe. This systematic review confirmed that FcRn is expressed in the nasal airway and the olfactory epithelium, and that FcRn may play a role in IgG and/or IgG-derived molecule-transcytosis across the airway epithelium. However, additional research is needed to better characterize the pharmacokinetic and pharmacodynamic properties of biologics after their intranasal delivery.
Topics: Animals; Biological Products; Biological Transport; Biomarkers; Drug Delivery Systems; Gene Expression; Histocompatibility Antigens Class I; Humans; Nasal Mucosa; Protein Binding; Receptors, Fc; Transcytosis
PubMed: 34204226
DOI: 10.3390/ijms22126475 -
Vaccines May 2021The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their... (Review)
Review
The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936-0.954) and 80.2% (95% CI 0.56-0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939-0.997) and second (98.2%; 95% CI 0.980-0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines' adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.
PubMed: 34066475
DOI: 10.3390/vaccines9050467 -
Pathogens (Basel, Switzerland) May 2021is the zoonotic parasite responsible for toxoplasmosis in warm-blooded vertebrates. This systematic review compares and evaluates the available knowledge on... (Review)
Review
is the zoonotic parasite responsible for toxoplasmosis in warm-blooded vertebrates. This systematic review compares and evaluates the available knowledge on enzyme-linked immunosorbent assays (ELISAs), their components, and performance in detecting antibodies in animals. Four databases were searched for published scientific studies on and ELISA, and 57 articles were included. Overall, indirect (95%) and in-house (67%) ELISAs were the most used types of test among the studies examined, but the 'ID Screen Toxoplasmosis Indirect Multi-species' was common among commercially available tests. Varying diagnostic performance (sensitivity and specificity) and Kappa agreements were observed depending on the type of sample (serum, meat juice, milk), antigen (native, recombinant, chimeric) and antibody-binding reagents used. Combinations of recombinant and chimeric antigens resulted in better performance than native or single recombinant antigens. Protein A/G appeared to be useful in detecting IgG antibodies in a wide range of animal species due to its non-species-specific binding. One study reported cross-reactivity, with and spp. This is the first systematic review to descriptively compare ELISAs for the detection of antibodies across different animal species.
PubMed: 34063342
DOI: 10.3390/pathogens10050605 -
Expert Review of Vaccines Jul 2021: Cancer neoantigens represent important targets of cancer immunotherapy. The goal of cancer neoantigen vaccines is to induce neoantigen-specific immune responses and...
: Cancer neoantigens represent important targets of cancer immunotherapy. The goal of cancer neoantigen vaccines is to induce neoantigen-specific immune responses and antitumor immunity while minimizing the potential for autoimmune toxicity. Advances in sequencing technologies, neoantigen prediction algorithms, and other technologies have dramatically improved the ability to identify and prioritize cancer neoantigens. Unfortunately, results from preclinical studies and early phase clinical trials highlight important challenges to the successful clinical translation of neoantigen cancer vaccines.: In this review, we provide an overview of current strategies for the identification and prioritization of cancer neoantigens with a particular emphasis on the two most common strategies used for neoantigen identification: (1) direct identification of peptide ligands eluted from peptide-MHC complexes, and (2) next-generation sequencing combined with neoantigen prediction algorithms. We highlight the limitations of current neoantigen prediction pipelines, and discuss broader challenges associated with cancer neoantigen vaccines including tumor purity/heterogeneity and the immunosuppressive tumor microenvironment.: Despite current limitations, neoantigen prediction is likely to improve rapidly based on advances in sequencing, machine learning, and information sharing. The successful development of robust cancer neoantigen prediction strategies is likely to have a significant impact, with the potential to facilitate cancer neoantigen vaccine design.
Topics: Antigens, Neoplasm; Cancer Vaccines; Humans; Immunotherapy; Neoplasms; Tumor Microenvironment
PubMed: 34047245
DOI: 10.1080/14760584.2021.1935248 -
Frontiers in Immunology 2021Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical...
Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies.
Topics: Animals; Antibodies, Bispecific; Antibody Specificity; Binding Sites, Antibody; Biotechnology; Drug Design; Epitopes; Humans; Immunotherapy; Protein Engineering; Recombinant Proteins; Translational Research, Biomedical
PubMed: 34025638
DOI: 10.3389/fimmu.2021.626616