فهرست مطالب
- Volume:8 Issue: 2, 2021
- تاریخ انتشار: 1401/09/08
- تعداد عناوین: 16
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Pages 1-3
Sinopharm (BBIBP-CorV) is an inactivated whole-virus COVID-19 vaccine. The phase 3 trial showed an efficacy of up to 78% in preventing symptomatic COVID-19 infections. However, there have been questions raised regarding in its efficacy in older people. In this paper, several lessons are highlighted from this. Firstly, there is a need to take into account the heterogeneity of COVID-19 vaccine studies, such as representation of older people; and whether the results are generalizable to the target population of immunization programmes. Secondly, for older people, antibody responses alone may not indicate the level of protection afforded by vaccines, as cell mediated immunity is a better marker of immunity. Finally, suggestions are given to improve the immune response in older people, such as heterologous vaccination and booster doses.
Keywords: COVID-19, Aged, Older adults, Sinopharm BBIBP-CorV -
Pages 4-16Introduction
The virulent Newcastle disease virus (NDV) strains cause an economically important infectious disease in poultry. The common vaccination program with genotype II NDV strains is routinely practiced to provide a better protection level against Newcastle disease (ND). Nevertheless, the emergence of new antigenic and genetic variants within the circulating NDVs raises the importance of improved control strategies. The genotype VII NDV is associated with many of the most recent outbreaks of the disease worldwide.
MethodsWe evaluated the impacts of genetic divergence between the genotypes II and VII on the immunity against NDV to choose a suitable vaccine virus candidate by focusing on the F and HN proteins. Comparative bioinformatics analyses based on B- and T-cell epitopes binding affinity, protein secondary structure and physicochemical properties predictions were applied for genotypes II and VII.
ResultsAlthough the results showed more differences in HN protein than F protein, there was no major difference between the predicted antigenicity values, epitope regions, affinity binding to MHC-I and MHC-II, secondary structures, surface accessibility, and stability of these immunogens between genotypes II and VII.
ConclusionThe results suggest that genotype II-based live vaccines can induce immune responses against NDV; however, an inactivated vaccine formulated by genotype VII should be considered in combination with the traditional live vaccine to provide better protection in controlling programs against ND.
Keywords: Newcastle disease virus, vaccine, genetic divergence, immune responses -
Pages 17-25
Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that detect pathogen associated molecular patterns and activate innate and adaptive immune system. Coronaviruses can be detected via TLRs through their biological materials such as ribonucleic acids, glycoproteins and CpG motifs. During COVID-19 pandemic, different strategies have been used for combating SARS-CoV-2 to initiate a proper and balanced immune response through TLRs or other PRRS. Understanding the trigerred TLR signaling pathways during coronavirus infections would assist to understand the control and defense mechanisms against these viral diseases. In this review, we summarize different studies on the use and function of of TLRs and their signaling pathways as vaccines/adjuvants or therapeutic agents against coronavirus infections. Since the pandemic is ongoing and there still many unknowns with respect to COVID-19 immunology, we highlight the role of TLRs and their agonists/antagonists in previous coronavirus infections, and show their potential role in the current SARS-CoV-2 immunopathology.
Keywords: TLRs, SARS, MERS, COVID-19, Agonist -
Pages 26-27
Corneal transplantation is among the most successful organ transplantations in humans due to its immune privilege. This owes to lack of blood and lymph vessels and the absence of major histocompatibility complex antigen presenting cells (MHC-II APCs) in the cornea. However, vaccination may trigger MHC-II response as well as antigenic cross reactivity, resulting in allograft rejection. This has been reported earlier in sporadic cases after influenza and yellow fever vaccines. With the rampant vaccination and booster doses against COVID-19, similar episodes of post-vaccination graft rejection in penetrating and lamellar keratoplasties have been reported. We had reported a case of corneal graft rejection post covid vector vaccine which recovered with steroid medications. Allograft rejection with various subtypes of vaccination opens the door to comprehend immune privilege mechanisms and prophylaxis against organ rejection. Clinicians and patients are advised to be alert to this possibility, for prompt recognition as well as treatment of post-vaccination corneal graft rejection.
Keywords: Vector vaccine, Immune privilege, COVID-19, Corneal graft rejection -
Pages 28-38Introduction
Cervical cancer is one of main causes of cancer death in women, especially in developing countries. Therefore, a low-cost broad-spectrum preventive vaccine is immediately needed. The RG-1 epitope of L2 protein is a major cross-neutralizing epitope but has low immunogenicity. This defect can be overcome by using built-in adjuvants such as TLR agonists and bacterial toxoid epitopes. To address this issue, we designed an epitope-based vaccine against HPV16 using immunoinformatic tools.
MethodsThe HPV16 RG-1 epitope was linked to built-in adjuvants including the D1 domain of flagellin and RS09 epitope as TLR agonists, and a tetanus toxoid epitope for induction of immune responses. Using immunoinformatic tools, the immunological characteristics of the construct were evaluated. In the first step, MHC-I and II binding, CD4+ T cell immunogenicity prediction, and in the second step, immunogenicity simulation of the construct were investigated.
ResultsMHC-I and II predicted epitopes showed a high potentiality to bind to mice and human MHC alleles. The results of the binding of the RG-1 epitope to MHC-I and MHC-II showed that RG-1 could induce humoral and cellular immune response while fused to three built-in adjuvants. Also, the CD4+ immunogenicity assessment results predicted that several epitopes in the designed construct, including epitopes of D1 domain and tetanus toxoid P2 epitope, behaved as potentially strong Th inducers. The immunogenicity simulation results showed that the construct could potentially provide sufficient antigen, and induce suitable humoral and cellular immune responses.
ConclusionThe development of new vaccine strategies has been the focus of several studies. The results showed that the designed construct can potentially provide an effective model for developing a preventive vaccine candidate against a variety of HPV genotypes.
Keywords: HPV16 RG-1, Built-in adjuvants, TLR agonists, Immunoinformatic, immunogenicity simulation -
Pages 39-43Introduction
Faecalibacterium prausnitzii is an important member of human gut microbiota with a critical function in the health of humans through the induction of inflammatory and immune responses leading to intestinal hemostasis. Microbiota-induced extracellular vesicles (EVs) were presented as a novel communication pathway between microbiota and the host that are capable of imposing positive effects on the host. Recently, EV-based treatments have been evaluated in different studies, and using EVs derived from microbiota has been recommended in recent studies as post-vaccination adjuvants. Accordingly, in the present study, the effects of various EV concentrations on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) and fasting-induced adipose factor (FIAF) genes were evaluated and optimized in the human epithelial colorectal adenocarcinoma (Caco-2) cell line.
MethodsThe effects of the extracted EVs from F. prausnitzii on the PPARγ and FIAF gene expression were investigated in the Caco-2 cell line via cell culture and quantitative real-time PCR. The obtained outcomes were then compared with those of our previous study (concentrations of 50 and 100 µg/ml).
ResultsIt was shown that F. prausnitzii EVs (150 µg/ml) significantly increased PPARγ and FIAF gene expression in the Caco-2 cell line, relative to previous studies conducted by our team.
ConclusionConsidering the positive impact of F. Prausnitzii EVs on the studied genes’ expression in the present study, the EVs of the bacterium will be proposed as new post-vaccination adjuvants in people suffering from intestinal barrier disorders such as inflammatory bowel disease patients. However, more studies should be performed in this respect.
Keywords: F. prausnitzii, EVs, PPARγ, FIAF, Caco-2 cell line -
Pages 44-47Introduction
Multiple myeloma is the second most common blood malignancy which has remained incurable with current therapies. However, gene therapy using suicide viral vectors such as adenoviral vectors appear more promising than other treatments. The aim of this study was to evaluate the effects of an adenoviral vector vaccine candidate containing HSV-TK gene on tumor reduction and autophagy mechanism in animal model.
MethodsMyeloma tumor was created in mouse models using myeloma SP2/0 cell line. Three groups of negative control, positive control and target group of BALB/c mice were formed. Candidates for the Ad-HSV-tk /GCV vaccine at high titer (108) were then injected three times every 72 hours at target mice and metformin was injected into the control group for 12 consecutive days. Tumor size was measured in all 15 mice studied every three days, and finally, three days after the last dose of the vaccine, the tumors were removed for Western blotting and LC3B expression.
ResultsExamination of tumor size showed that injection of the vaccine and autophagy-inducing drug reduced tumor size compared to the negative control group. Western blotting indicated that LC3B expression was significantly higher in the target and positive control groups than in the negative control group. (Mean Diff: -0.4921; P value < 0.05; q: 7.911).
ConclusionThe results suggest that Ad-HSV-tk/GCV vaccine candidate was able to induce autophagy and reduce the growth of tumor cells in the animal model studied due to the ability of adenovirus to induce the immune system response, the anti-myeloma nature of adenovirus and the function of HSV-tk suicide gene
Keywords: Vaccine, Suicide gene, Autophagy, HSV-tk, GCV -
Pages 48-54
CoronaVirus Disease 2019 (COVID-19) is a viral infection caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), which is effective worldwide and has killed more than 6 million patients until today. Hyper secretion of proinflammatory cytokines triggered by a viral infection that cannot be eliminated by the immune system and an ongoing hyper-inflammatory state primarily in the lung seem to be the main causes of death. Many mechanisms have been proposed in the pathogenesis of the cytokine storm associated with COVID-19. Poor viral clearance and persistence of a strong cytokine response despite inadequate antiviral immunity appear to be the main mechanisms underlying the pathogenesis. The diagnosis can be made easily by clinical features, imaging techniques, and nasopharyngeal PCR. The diagnosis of this hyper-inflammatory state developing in the course of COVID-19 can be made based on clinical features, abnormally high ferritin, CRP, D-dimer levels, and rapidly progressive radiological findings. In addition to the antiviral and supportive treatments developed for COVID-19, CoronaVirus Disease 2019 (COVID-19) is a viral infection caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), which is globally influential and has killed more than 6 million patients until today. Hyper-secretion of pro-inflammatory cytokines triggered by the viral infection that cannot be eliminated by the immune system and an ongoing hyper-inflammatory state primarily in the lung seem to be the major causes of death. The mechanisms proposed to explain the pathogenesis of the cytokine storm associated with COVID-19 included poor viral clearance and persistent robust cytokine response despite inadequate antiviral immunity. The diagnosis can be made easily by clinical features, imaging techniques, and nasopharyngeal PCR. The diagnosis of this hyper-inflammatory state in a patient with COVID-19 can be made with rapid deterioration in clinical features, and laboratory findings including abnormally high serum CRP, ferritin and D-dimer levels, and rapidly progressive pulmonary radiological findings. In addition to the anti-viral and supportive treatments, corticosteroids, IL-1, or IL-6 receptor blockers are frequently used to suppress the increased cytokine response. corticosteroids, IL-6 blockers, or IL-1 blockers are frequently used to suppress the increased cytokine response.
Keywords: COVID-19, Cytokine Storm, Macrophage Activation Syndrome, IL-1 blockage, IL-6 blockage -
Pages 55-61Introduction
Cancer immunotherapy is one of the effective treatment methods that provide a better quality of life with limited side effects for patients. Carcinoembryonic Antigen (CEA) can be an appropriate target for cancer immunotherapy.
MethodsA lentivector expressing CEA antigen, pCDH-CEA, was constructed by cloning CEA cDNA downstream of the CMV promoter. The constructed plasmid was co-transfected with helper plasmids, into Lenti-X 293 T cells. The lentivector-containing supernatant was collected. Titers of the CEA- lentivector were estimated using the RT-PCR method. The CT26 cells were then infected by CEA- lentivector. Puromycin as a selective antibiotic was added to the culture for 2 weeks to select CEA-positive cells. The ability to produce tumors in BALB/c mice was investigated.
ResultsThe results showed that CEA expressing lentivector plasmids and the two other helper plasmids could be transfected into Lenti-X 293T cells efficiently and packaged successfully as a pseudo-lentivector. The detection of CEA mRNA and protein expression in the 6th and 14th passages of CT26-CEA cells was confirmed in the engineered stable cell line. Tumor formation was confirmed in cell inoculated mice.
ConclusionCT26-CEA cell line with stable expression of CEA can be used as a suitable tumor model to facilitate research on colorectal cancer in vitro and in mice models; therefore, it could be served as a valuable tool for cancer immunotherapy
Keywords: Cancer immunotherapy, CEA, lentivector, RT-PCR, ELFA -
Pages 62-64
Healthcare workers (HCW) are at an increased risk of acquiring vaccine preventable diseases (VPD) due to their higher patient exposure at the workplace. In this context, they form an important target population for vaccination. The authors of this article wanted to explore into the history of vaccination, the risk profile of the health care workers and the current vaccines recommended for the health care workers. Looking forward, vaccine uptake among the healthcare workers can be improved by measures such as conducting periodic annual health check ups and establishing written hospital vaccination policies.
Keywords: Healthcare Worker, Immunisation, Vaccination, Vaccine Preventable Diseases -
Pages 65-87Introduction
To prevent pneumococcal infections, especially meningitis and bacteremia, and to overcome the serotype-dependent limitation of polysaccharide-based vaccines, the development of conserved protein-based vaccines is essential. This study aimed at investigate the in-silico analysis and epitope mapping of pneumococcal DnaJ for the first time, and to design the multi-epitope based vaccines with different categories by focusing on induction of both humoral and cellular immunities.
MethodsWe predicted B- and T-cell epitopes, IL-4, IL-17, IL-10, and IFN-γ inducer epitopes of DnaJ using Immunoinformatics tools. The immunogenicity and conservation score of the predicted epitopes among pneumococcal prevalent clinical serotypes, the immune simulation of DnaJ administration in mammals and potential regions involved in DnaJ-TLRs interactions were analyzed. Finally, we proposed three classes of multi-epitope DnaJ-based vaccine candidates.
ResultsThis protein had 24 and 15 predicted linear B-cell and helper T-cell epitopes, respectively, with a conservation score of 86-100% among prevalent clinical pneumococcal serotypes. DnaJ also had many IL-4 and IFN-γ inducing epitopes and was considered an IL-10 and IL-17 inducer protein. The immune simulation showed induction of both humoral and cellular immunity against DnaJ. The residues at positions 274, 280, 292, 297, 300, 316-319, 333, 336-340, 358, 363-366, and 372 were predicted to be involved in DnaJ-TLR2 and DnaJ-TLR4 interactions. Three classes of proposed DnaJ-based constructs were based on only B-cell epitopes, only helper T-cell epitopes, and multi-epitopes of B- and T-cell and IL-17 epitopes.
ConclusionThe results showed that although DnaJ has been reported to play an important role in cellular immunity, our results indicated the high potential of DnaJ to stimulate mucosal, humoral, and cellular immunity.
Keywords: Streptococcus pneumoniae, DnaJ, Vaccine Candidate, In-silico, Iran -
Pages 88-92Introduction
This study aimed to evaluate the baseline characteristics of patients infected with SARS-CoV-2, after receiving first or second doses of COVID-19 vaccine.
MethodsIn this cross-sectional study, we examined 100 patients with SARS-CoV-2 infection after vaccination and collected demographic characteristics and history of underlying diseases, lung involvement, and severity of the disease, as well as the type of vaccine received and the duration of onset of the diseases symptoms after vaccination. The relationship between the disease severity and variables was evaluated by the bivariate analysis. Multiple logistic regression model was performed to predict the severity of the disease by calculating the odds ratios and 95% confidence intervals (CIs).
ResultsThe mean±SD age of COVID-19 patients was 62.54±14.93 years. 59% of patients were male. The mean interval between vaccination and onset of symptom disease was 4.95 days. In bivariable analysis, there was a difference between the mean of the lung involvement in CT scan, O2 saturation, hypertension (HTN), and Severity of the disease (p < 0.001). In multiple logistic regression analysis, HTN (OR: 5.6, 95CI:1.07-25.5, p = 0.04), O2 saturation < 90% (OR:1.53, 95% CI: 1.39-2.92, p =0.003) and lung involvement ≥ 30% in CT scan were predictors of disease severity.
ConclusionDue to the short time interval between COVID-19 vaccination and the disease symptoms in this study, it is recommended all people with any symptom of disease to avoid the vaccination
Keywords: SARS‐CoV‐2, COVID-19 vaccine, Cross-sectional study -
Pages 93-101Introduction
Vaccine hesitancy is a global phenomenon and vaccination efforts against the Coronavirus Disease 2019 (COVID-19) pandemic may be hampered by it. This study assessed the acceptance rate of COVID-19 vaccination at different hypothetical efficacy and safety levels in Nigeria.
MethodsThis web-based study was conducted among a selected Nigerian population between the month of February and May 2021 using an online self-administered structured questionnaire hosted by Survey Monkey. WhatsApp, Twitter and Facebook were used to disseminate the invitation to take the poll.
ResultsThe finding of this study revealed that a larger proportion of the participants were males (53.9%), within the age group of 31-40 years (25.6%) and earn an average income of less than $500 per month. Individuals between the ages of 21 and 30 years and 31 to 40 years showed the highest levels of acceptability for the COVID-19 vaccine at 95% efficacy and 5% adverse effects. The older age group (>51 years and above) had the least vaccine acceptance rate (3.3%) at 75% vaccine efficacy and 20% side effect. Respondents who held the belief that vaccinations are essential for their health had a higher chance to accept the COVID-19 vaccine with OR: 0.76; 50%CI (0.00-0.00), OR: 95%CI (0.000-0.000), OR: 1.23; 95%CI (0.193-7.860) and OR: 0.696; 95%CI (0.048-10.047) based on religion, the occurrence of diabetes, pulmonary disease, and Hypertension, respectively.
ConclusionThe results of this research indicate that vaccine acceptance rates are negatively correlated with participants' ages.
Keywords: Acceptance, COVID-19, Efficacy, Nigeria, safety, Vaccine -
Attitude, Perception and Concern towards Children’s Vaccination amidst COVID-19 Pandemic among Selected Workers in a Nigerian PopulationPages 102-111Introduction
The coronavirus disease 2019 (COVID-19) is a vaccine-preventable disease amongst all ages; however, parental attitudes, perceptions and concerns towards children’s vaccination can hamper immunization efforts and leave this vulnerable group of the society unprotected. The aim of this study is to assess the attitude, perception and concern towards children’s vaccination amidst the COVID-19 Pandemic among selected workers in a Nigerian population.
MethodsThis web-based study was conducted among a selected Nigerian population between the month of February and May 2021 using an online self-administered structured questionnaire hosted by Survey Monkey. The invitation to take part in the poll was sent out to a total of 180 persons through social networking platforms including Facebook, Twitter, and WhatsApp. Version 25 of the Statistical Package for the Social Sciences (SPSS) was used to analyze the data collected and results presented using tables, bar charts and pie charts. The cutoff point was established at a level of significance equal to P < 0.05.
ResultsVaccine hesitant score on childhood acceptance rates shows that 28 (15.6%) had low acceptance rates, 125 (69.4%) had moderate acceptance rates, and 27 (15.0%) had high acceptance rates. There was significant association between age and overall vaccine hesitance on children’s vaccination acceptance rates at χ2 = 16.804, P = 0.032.
ConclusionMore than two-thirds of study participants supported children's vaccination. Those with low compliance may lack a realistic perception of infection risk, poor-quality information about immunizations and the disease, and general understanding.
Keywords: Attitude, Children, Concern, COVID-19, Perception, Vaccination -
Prevalence and Genetic Polymorphism of HLA-B*15 in the North Indian Population: Insights into SJS/TEN Prevention, Vaccines and Clinical TrialsPages 112-116Introduction
Since HLA-B*15:02 is a biomarker for carbamazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in certain Asian populations, the United States food and drug administration (USFDA) recommends HLA-B*15:02 screening before carbamazepine administration in Asian and other communities. Several published reports across the globe suggested a strong association of HLA-B*15 with carbamazepine-induced hypersensitivity reactions.
MethodsThis study was conducted to estimate the prevalence and the genetic polymorphism of HLA-B*15 in the North Indian population (N=5469) by PCR sequence-specific oligonucleotide probe (SSOP) genotyping of the HLA-B locus.
ResultsThe total allelic variants of HLA-B*15 identified amongst the studied samples were 17. The most frequent among these was HLA-B*15:17 (2.030%). Subsequently, HLA -B* 15:01 (1.463%) and B*15:02 (1.225%) were more frequent. Further, 185 HLA-B*15 genotypes were seen among the studied population with which the most frequent were HLA-B*15:17-40:06(0.402%), HLA-B*15:17-35:03 (0.366%) and HLA-B*15:02-40:06 (0.347%).
ConclusionThis information highlights the prevalence and diversity of HLA-B*15 genotyping and its importance in the screening of carbamazepine-induced SJS/TEN in the North Indian population where the prevalence of HLA-B*15 allelic variants was on the higher side. Further, this baseline information could be further explored in the understanding of the pathogenesis of the disease and may contribute valuable information for designing effective vaccines and clinical trials.
Keywords: HLA-B, HLA-B*15 allele, HLA-B*15 gene polymorphism, Carbamazepine-induced hypersensitivity reactions -
Phylogenetic Analysis, Cloning and Expression of Delta Amastin Encoding Gene from Leishmania major as a Vaccine CandidatePages 117-126Introduction
Amastin is a surface glycoprotein in Leishmania species and one of the most important vaccine candidates due to its involvement in pathogenesis and being an essential virulence factor for parasite replication within the mammalian host cells. There are more than 60 copies of Amastin gene per genome of the parasite.
MethodsFollowing phylogenetic analysis, a selected Amastin sequence was optimized and cloned with signal peptide in Escherichia coli. The recombinant protein was evaluated by SDG-PAGE and a specific antibody by Western blotting.
ResultsAmong the Amastin sequences within different chromosomes of Leishmania major, the main type known as delta Amastin (primary distributed on chromosome 34) could be expressed in E. coli host and was confirmed by SDG-PAGE and Western blotting.
ConclusionDue to its copy number and evolutionary conservation and its role in pathogenesis, δ-Amastin is considered as an important vaccine candidate against leishmaniasis which could be expressed as a recombinant protein in E. coli.
Keywords: Leishmania, Amastin, Recombinant, Vaccine