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Viruses Mar 2022During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4... (Review)
Review
During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4 and CD8 T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4 T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.
Topics: Animals; CD8-Positive T-Lymphocytes; Disease Progression; HIV Infections; Humans; Immunoglobulins; Lymphocyte Activation; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus
PubMed: 35336991
DOI: 10.3390/v14030581 -
Vaccines Mar 2023Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected over 600 million individuals and... (Review)
Review
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected over 600 million individuals and caused nearly 7 million deaths worldwide (10 January 2023). Patients with renal disease undergoing hemodialysis are among those most adversely affected, with an increased predisposition to SARS-CoV-2 infection and death. This systematic review aimed to pool evidence assessing the humoral response of hemodialysis patients (HDP) post-mRNA SARS-CoV-2 vaccination. A systematic search of the literature was performed through MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers up to 10 January 2023. Cohort and case-control studies were included if they reported an immune response in one group of patients undergoing hemodialysis who received mRNA SARS-CoV-2 vaccination compared with another group of patients receiving the same vaccine but not on hemodialysis. The methodological quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was not deemed appropriate due to the high heterogeneity between studies. From the 120 studies identified, nine (n = 1969 participants) met the inclusion criteria. Most studies (n = 8/9, 88%) were of high or medium methodological quality (≥6/9 stars). The results revealed that HDP developed lower antibody levels across all timepoints post-vaccination when compared with controls. Patients with chronic kidney disease elicited the highest antibody immune response, followed by HDP and, lastly, kidney transplant recipients. Overall, post-vaccination antibody titers were comparatively lower than in the healthy population. Current results imply that robust vaccination strategies are needed to address waning immune responses in vulnerable populations.
PubMed: 37112636
DOI: 10.3390/vaccines11040724 -
Epigenetics Aug 2021N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate...
N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate network architecture by which m6A epitranscriptome impacts on immune response and function. However, it was only until recently that the mechanisms underlying the involvement of m6A modification in immune system were uncovered. Here, we systematically review the m6A involvement in the regulation of innate and adaptive immune cells. Further, the interplay between m6A modification and anti-inflammatory, anti-viral and anti-tumour immunity is also comprehensively summarized. Finally, we focus on the future prospects of m6A modification in immune modulation. A better understanding of the crosstalk between m6A modification and immune system is of great significance to reveal new pathogenic pathways and to develop promising therapeutic targets of diseases.
Topics: Adenosine; DNA Methylation; Immune System; Logic
PubMed: 33070685
DOI: 10.1080/15592294.2020.1827722 -
JAMA Network Open Apr 2022Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination. (Meta-Analysis)
Meta-Analysis
Immunogenicity and Risk Factors Associated With Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant: A Systematic Review and Meta-Analysis.
IMPORTANCE
Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination.
OBJECTIVE
To summarize current evidence on vaccine responses and identify risk factors for diminished humoral immune response in recipients of SOT.
DATA SOURCES
A literature search was conducted from existence of database through December 15, 2021, using MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov.
STUDY SELECTION
Studies reporting humoral immune response of the COVID-19 vaccines in recipients of SOT were reviewed.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data from each eligible study. Descriptive statistics and a random-effects model were used. This report was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from December 2021 to February 2022.
MAIN OUTCOMES AND MEASURES
The total numbers of positive immune responses and percentage across each vaccine platform were recorded. Pooled odds ratios (pORs) with 95% CIs were used to calculate the pooled effect estimates of risk factors for poor antibody response.
RESULTS
A total of 83 studies were included for the systematic review, and 29 studies were included in the meta-analysis, representing 11 713 recipients of SOT. The weighted mean (range) of total positive humoral response for antispike antibodies after receipt of mRNA COVID-19 vaccine was 10.4% (0%-37.9%) for 1 dose, 44.9% (0%-79.1%) for 2 doses, and 63.1% (49.1%-69.1%) for 3 doses. In 2 studies, 50% of recipients of SOT with no or minimal antibody response after 3 doses of mRNA COVID-19 vaccine mounted an antibody response after a fourth dose. Among the factors associated with poor antibody response were older age (mean [SE] age difference between responders and nonresponders, 3.94 [1.1] years), deceased donor status (pOR, 0.66 [95% CI, 0.53-0.83]; I2 = 0%), antimetabolite use (pOR, 0.21 [95% CI, 0.14-0.29]; I2 = 70%), recent rituximab exposure (pOR, 0.21 [95% CI, 0.07-0.61]; I2 = 0%), and recent antithymocyte globulin exposure (pOR, 0.32 [95% CI, 0.15-0.71]; I2 = 0%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the rates of positive antibody response in solid organ transplant recipients remained low despite multiple doses of mRNA vaccines. These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses and to study monoclonal antibody prophylaxis among recipients of SOT who are at high risk of diminished humoral response.
Topics: COVID-19; COVID-19 Vaccines; Child, Preschool; Humans; Immunity, Humoral; Organ Transplantation; RNA, Messenger; Risk Factors; SARS-CoV-2
PubMed: 35412626
DOI: 10.1001/jamanetworkopen.2022.6822 -
Cancers Feb 2020Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require... (Review)
Review
Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, = 16; patients, = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24-1.91; = 0.01 and HR = 1.34, 95% CI: 1.02-1.76; = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41-4.43; < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22-1.87; < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.
PubMed: 32120803
DOI: 10.3390/cancers12030546 -
Expert Review of Vaccines 2024This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV).
METHODS
We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls.
RESULTS
Twenty-nine RCTs ( = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28-15.41; I = 33%; < 0.01) between the two groups. There was a significant difference in RR of adverse events (AEs) of EVV (RR 1.49; 95% CI 1.27-1.74; I = 88%; < 0.01), although no difference in RR of serious AE (SAE) between the two groups. Subgroup analysis showed that there was no significant difference in RR of AEs for DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines, compared with controls.
CONCLUSIONS
The DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines are likely to be safe and immunogenic, tending to support the vaccination against Ebola disease. These findings should provide much-needed evidence for public health policy makers to develop preventive measures based on disease prevalence features and socio-economic conditions.
Topics: Adult; Humans; Ebola Vaccines; Randomized Controlled Trials as Topic; Hemorrhagic Fever, Ebola; Vaccination; Antibody Formation; Ebolavirus
PubMed: 38112249
DOI: 10.1080/14760584.2023.2296937 -
PloS One 2022Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses.
OBJECTIVE
Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses.
METHODS
Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20-22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described.
RESULTS
There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio.
CONCLUSIONS
The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42021261684).
Topics: 2019-nCoV Vaccine mRNA-1273; Adult; Animals; Antibodies, Viral; Antibody Formation; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Databases, Factual; Female; Humans; Immunogenicity, Vaccine; Immunoglobulin G; Pregnancy; Registries; SARS-CoV-2; Vaccination; mRNA Vaccines
PubMed: 35108277
DOI: 10.1371/journal.pone.0261350 -
International Journal of Implant... Jul 2022There are rising concerns about titanium hypersensitivity reaction regarding dental endosseous implants. This review aims to summarize and compare the validity and... (Review)
Review
PURPOSE
There are rising concerns about titanium hypersensitivity reaction regarding dental endosseous implants. This review aims to summarize and compare the validity and reliability of the available dermatological and laboratory diagnostic tests regarding titanium hypersensitivity. The following PICO design was used: In Patients with titanium dental implants (P) does epicutaneous testing (ECT) (I), compared to lymphocyte transformation test (LTT) or Memory Lymphocyte Immunostimulation Assay (MELISA) (C) detect hypersensitivity reactions (O)? A literature search was performed including all studies dealing with this topic. Studies regarding orthopedic implants were excluded.
METHODS
Three databases (MEDLINE PubMed, Cochrane Library, SciELO) were screened for suitable studies and an additional manual search was also performed. Literature regarding hypersensitivity reactions in orthopedic implants, hypersensitivity reactions regarding implants not related to dental or maxillofacial surgery, animal studies and in vitro studies were excluded. A quality assessment of all selected full-text articles was performed. Randomized, controlled trials were evaluated with the Cochrane Risk of Bias Tool I. Cohort studies were assessed according to the New Castle-Ottawa Scale and case series according to Moga et al. (Development of a quality appraisal tool for case series studies using a modified Delphi technique. 2012).
RESULTS
10 studies were included in the quantitative synthesis and available for the endpoint diagnostics of intolerance reactions to titanium dental implants: 2 clinical studies, 7 cohort studies and 1 case series. The potential for bias (internal validity) for these studies was overall rated as high.
CONCLUSIONS
The study of the available literature regarding ECT and MELISA or LTT in patients with suspected titanium hypersensitivity showed inconsistent results in terms of reliability and validity and thus, those tests should be regarded cautiously. There is strong evidence that titanium hypersensitivity in dental implants is associated with innate immunity: unspecific pro-inflammatory responses due to particle induced hyperreactivity of macrophages or toxicological responses especially towards nanoparticles rather than activation of the adaptive immune system. Therefore, tests detecting allergies do not seem expedient and inflammatory clinical signs should be regarded as leading parameters.
Topics: Animals; Dental Implants; Diagnostic Tests, Routine; Humans; Hypersensitivity; Reproducibility of Results; Titanium
PubMed: 35819566
DOI: 10.1186/s40729-022-00428-0 -
International Journal of Environmental... Jun 2022Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still limited. Several studies have reported the duration of antibodies following cholera; however, systematic reviews including a quantitative synthesis are lacking.
OBJECTIVE
To meta-analyze cohort studies that have evaluated vibriocidal, cholera toxin B subunit (CTB), and lipopolysaccharide (LPS) antibody levels following a clinical cholera case.
METHODS
Design: Systematic review and meta-analysis. We searched PubMed and Web of science for studies assessing antibodies against in cohorts of patients with clinical cholera. Two authors independently extracted data and assessed the quality of included studies. Random effects models were used to pool antibody titers in adults and older children (aged ≥ 6 years). In sensitivity analysis, studies reporting data on young children (2-5 years) were included.
RESULTS
Nine studies met our inclusion criteria for systematic review and seven for meta-analysis. The pooled mean of vibriocidal antibody titers in adults and older children (aged ≥ 6 years) was 123 on day 2 post-symptom onset, which sharply increased on day 7 (pooled mean = 6956) and gradually waned to 2247 on day 30, 578 on day 90, and 177 on day 360. Anti-CTB IgA antibodies also peaked on day 7 (pooled mean = 49), followed by a rapid decrease on day 30 (pooled mean = 21), and further declined on day 90 (pooled mean = 10), after which it plateaued from day 180 (pooled mean = 8) to 360 (pooled mean = 6). Similarly, anti-CTB IgG antibodies peaked in early convalescence between days 7 (pooled mean = 65) and 30 (pooled mean = 69), then gradually waned on days 90 (pooled mean = 42) and 180 (pooled mean = 30) and returned to baseline on day 360 (pooled mean = 24). Anti-LPS IgA antibodies peaked on day 7 (pooled mean = 124), gradually declined on day 30 (pooled mean = 44), which persisted until day 360 (pooled mean = 10). Anti LPS IgG antibodies peaked on day 7 (pooled mean = 94). Thereafter, they decreased on day 30 (pooled mean = 85), and dropped further on days 90 (pooled mean = 51) and 180 (pooled mean = 47), and returned to baseline on day 360 (pooled mean = 32). Sensitivity analysis including data from young children (aged 2-5 years) showed very similar findings as in the primary analysis.
CONCLUSIONS
This study confirms that serological antibody (vibriocidal, CTB, and LPS) titers return to baseline levels within 1 year following clinical cholera, i.e., before the protective immunity against subsequent cholera wanes. However, this decay should not be interpreted as waning immunity because immunity conferred by cholera against subsequent disease lasts 3-10 years. Our study provides evidence for surveillance strategies and future research on vaccines and also demonstrates the need for further studies to improve our understanding of immunity against cholera.
Topics: Adolescent; Adult; Antibodies, Bacterial; B-Lymphocytes; Child; Child, Preschool; Cholera; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Memory; Kinetics; Lipopolysaccharides; Vibrio cholerae O1
PubMed: 35742404
DOI: 10.3390/ijerph19127141 -
Journal of Biological Rhythms Jun 2024Molecular timing mechanisms known as circadian clocks drive endogenous 24-h rhythmicity in most physiological functions, including innate and adaptive immunity.... (Review)
Review
Molecular timing mechanisms known as circadian clocks drive endogenous 24-h rhythmicity in most physiological functions, including innate and adaptive immunity. Consequently, the response to immune challenge such as vaccination might depend on the time of day of exposure. This study assessed whether the time of day of vaccination (TODV) is associated with the subsequent immune and clinical response by conducting a systematic review of previous studies. The Cochrane Library, PubMed, Google, Medline, and Embase were searched for studies that reported TODV and immune and clinical outcomes, yielding 3114 studies, 23 of which met the inclusion criteria. The global severe acute respiratory syndrome coronavirus 2 vaccination program facilitated investigation of TODV and almost half of the studies included reported data collected during the COVID-19 pandemic. There was considerable heterogeneity in the demography of participants and type of vaccine, and most studies were biased by failure to account for immune status prior to vaccination, self-selection of vaccination time, or confounding factors such as sleep, chronotype, and shiftwork. The optimum TODV was concluded to be afternoon (5 studies), morning (5 studies), morning and afternoon (1 study), midday (1 study), and morning or late afternoon (1 study), with the remaining 10 studies reporting no effect. Further research is required to understand the relationship between TODV and subsequent immune outcome and whether any clinical benefit outweighs the potential effect of this intervention on vaccine uptake.
Topics: Humans; Circadian Rhythm; Vaccination; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Time Factors; Circadian Clocks
PubMed: 38459699
DOI: 10.1177/07487304241232447