VACCINE RESEARCH
Year:2020 | Volume:7 | Issue:2|Papers Count:16

The prevalence of allergic diseases has been on the rise during past decades. Epidemiological studies have shown that extensive exposure to bio-aerosols causes adverse health effects such as respiratory disorders, allergic reactions and infections. Aeroallergens are allergic airborne particles that disperse from environmental sources over great distances by air currents and ultimately are inhaled by, ingested by, or come into contact with individuals who have had no previous contact with the allergenic agent. The most important bioaerosols in Iran are pollen grains, molds, house dust mites, and animal dander causing many allergic reactions in the country every year. Geographical variation is an important role in the prevalence of allergic diseases, most likely due to different environmental factors. Therefore, identifying geographical and seasonal distribution of allergens not only enables us to warn patients to avoid them but also contributes significantly in the diagnosis, prevention and management of the progress of allergic disorders and provides the possibility of performing immunotherapy. The results of this survey about the most common aeroallergens in different geographic areas of Iran may provide proper prevention activities, vaccine production insights and therefore may reduce the treatment costs for allergic patients.

We report a case series of nine patients with confirmed coronavirus disease 2019 (COVID-19) in Tehran, Iran. This paper also reports narrative information on the signs and symptoms of the patients and discusses the potential immunologic perspective of the disease, especially with respect to the cytokine storm.

The skin is considered as the largest organ in the body, functioning as a barrier providing protection from the outside environment, but also performing essential immune functions through a complex network of epidermal and dermal cells that interact with each other. The basic principle of the vaccines is to induce protection against pathogens by simulating its interaction with the immune system, allowing to generate a memory immune response. To achieve this protection, the interaction and binding of both innate and adaptive immune responses is required. Intradermal (ID) delivery of vaccines achieves direct injection of the antigen into the dermis, where the largest numbers of immune cells are found (macrophages, dendritic cells, Langerhans cells, B and T lymphocytes, and mast cells, among others). It is a novel route that elicits antibody responses equivalent to other routes of administration but at lower doses, a phenomenon known as "dose saving". This route also allows for better thermo-stability of the antigen, fewer booster immunizations and, as a consequence, increased adherence to the vaccination regimens with less burden on the medical personnel. There are currently several vaccines for the ID administration on the market, and several more under development; with good safety profiles and efficacy rates. In this article, we review the most important aspects of the immune system within the skin, the pathways by which vaccines are applied to the skin intradermally to produce an adequate immune response, and also their advantages and disadvantages. The skin has important immune machinery, thanks to which both innate and adaptive immune responses merge. This interaction allows for the basis of vaccination: development of memory responses to various antigens, providing protection for the future re-exposures.

Introduction: Dendritic cells (DCs) play crucial roles in cellular immunity as the most powerful antigen presenting cells. They have been widely used for antigen delivery in vivo and in vitro. There are different ways to generate DCs and also gene transduction. In this study we introduce some optimization in order to produce high amount of well differentiated murine DCs for potential immunotherapy and vaccine development applications. Methods: Murine bone marrow cells were isolated from male BALB/c mice and the cells were cultured with complete RPMI in presence of the same ratio of IL-4 and GM-CSF. Some changes were made in the medium and the lysis buffer applications to increase the differentiation rate of the cells. Lentiviral virions were applied to transfer the genes of interest to DCs with no pre-maturation steps. CD11c, MHC-II, CD80 and CD86 were assessed by flow cytometry. Results: The optimized steps led to significant increase in number of the isolated cells. IL-4 usage in a similar dose to GM-CSF led to macrophage formation inhibition. Lentiviral virions resulted in successful gene delivery along with well-maturated DCs. Conclusion: The introduced optimized steps could be followed in different DC applications by using lentiviral virions to transduce DCs, independent of the pre-maturation steps.

Introduction: In India, only 56. 3% of children between one to two years of age have received full immunization. In some area, despite of good health care delivery system, immunization coverage is not reaching up to the mark due to some unaddressed issues. Therefore, identification of these determinants will help to improve the immunization status of each child. Methods: Community-based cross-sectional study was conducted in the field practice area of the Rural Health Training Centre (RHTC) affiliated to the medical college in Maharashtra, India. The sample of 350 participants was taken from 19 villages in the rural area and 17 administrative wards in the urban area by ‘ Probability Proportional to population Size’ method. All married women in 15-49 years of age, having child in the age group 13-24 months were included in the study. Results: 83. 71% children were fully immunized while remaining 16. 29% were either partially or unimmunized. The dropout rate for measles compared to BCG was 16. 3%. Main reasons for partial and un-immunization were lack of information and forgotten about the date. Occupation of mother, family type, parity, place of delivery and knowledge of immunization were significantly associated with immunization status of child. Conclusions: The determinants of immunization coverage if studied locally will help the programme managers to implement programme effectively to increase the overall coverage.

Introduction: Avian influenza virus causes severe economic losses to the poultry industry and has a great potential for becoming a pandemic threat for humans. The application of natural adjuvants has opened up new avenues toward reaching a highly efficient and safe vaccine in recent years. In this study, we investigated the adjuvant activity of interferon-induced myxovirus resistance (Mx) protein on chitosan-based H9N2 nanoparticles in a BALB/c mouse model. Methods: The inactivated H9N2 virus antigen was encapsulated in chitosan nanoparticles (NPs) using gelation method. Female BALB/c mice were randomly divided into four groups (n=10). Group A received the H9N2-loaded chitosan NPs mixing with Mx intranasally and was boosted twice with a 1-week interval. Group B received the H9N2-loaded chitosan NPs in the same manner. Mice in groups C and D received the chitosan NPs and PBS, respectively as negative controls. Body weights of the mice were measured at defined times. Blood samples were collected from the animals and their influenza-specific antibody titer was determined using ELISA. Results: The results demonstrated a higher antibody level in treated groups A and B as compared to the control samples. We also showed that the combination of Mx and chitosan could significantly induce an influenza-specific antibody titer, indicating synergistic effects of the applied adjuvant and NPs together. Conclusion: The formulation of H9N2 with Mx as an adjuvant and chitosan as a nanocarrier is a promising procedure for developing an efficient vaccine against avian influenza virus.

Introduction: The World Health Organization (WHO) recommends measles vaccination campaigns as an effective strategy that is required to halt and revert the burden of measles worldwide, especially in the African region. This is a review of the 2017/2018 measles campaign in South-south Zone, Nigeria. Methods: The WHO EPI cluster survey methodology was used to survey a total of 1260 households covering 1355 children aged 9-59 months, yielding a sufficient sample size to provide estimated zonal and state measles vaccine coverage. Data collection was done using census and survey program software and supplementary immunization activity module of vaccination coverage quality indicators while the analysis was run on Stata. Results: The measles vaccination and routine immunization coverage in the South-south zone of Nigeria were 87. 6% and 67. 6% respectively. While town criers/mobilizers (49. 6%) were the commonest source of information for the campaign, the lack of awareness (28. 4%) was the most important reason given by the mothers and care-givers for non-vaccination. Fever (6. 6%) was the most commonly reported adverse event following the immunization. Conclusion: The zonal vaccination coverage was less than the WHO recommended coverage that would be needed to stop the measles epidemic in Nigeria. Town criers were very useful for information dissemination. The lack of awareness was a major reason for non-vaccination.

Introduction: Poultry vaccines are used to immunize chickens against different diseases. Inactivated vaccines have been widely used to protect poultry against diseases such as infectious bursal disease (IBD). IBD is one of the most important viral immunosuppressive diseases in the poultry industry. This viral disease targets the immune organs. This study was aimed to evaluate the effect of an inactivated IBDV antigen on inducing the humoral immune response in Specific-Pathogen-Free (SPF) chickens. Methods: An infectious strain of bursal disease virus (IBDV) was isolated from an affected chicken bursa of Fabricius. Serological diagnostic tests and molecular experiments were carried out to identify the isolate. Different concentrations of formalin, beta propiolacton (BPL) and binary ethylenimine (BEI) were used for inactivation of IBDV. The samples of IBDV antigen were adjuvanted separately with ISA-70. Threeweek-old SPF chickens were divided into four groups. Groups 1, 2, and 3 received 0. 5 ml of the adjuvanted antigens subcutaneously and group 4 received PBS as negative control. Blood samples from each group were collected 4 weeks post-inoculation and the targets were measured by ELISA and serum neutralization test (SNT). Results: The lowest concentrations that could fully inactivate the infectivity of IBD virus were 2. 5 mM for BEI, 0. 15% for BPL and 0. 1% for formalin. Examination of the inactivated samples with 0. 1% formalin showed a decrease in antigenicity after 12 months. Treatment with 2. 5 mM BEI and 0. 15% BPL showed no apparent adverse effect on IBDV infectivity and showed a reliable inactivation. In the SPF chickens of all experimental groups, the antibody titers raised against IBDV were detected by ELISA. Conclusion: In the group which the virus was inactivated using BEI, the antigenicity stability was much better than others. Hence, BEI-inactivated IBDV is suggested for preparing more immunogenic, efficient and stable vaccines against IBD.

Introduction: There is a continued quest towards developing protective vaccines to halt and end the global pandemic of COVID-19 with the research predominantly driven by the developed world. Induction of herd immunity requires mass vaccination, and any avoidable delays would cause enormous health and economic losses. However, developing countries will experience extensive vaccine allocation challenges due to limited indigenous manufacturing and cold chain facilities. Methods: Literature searches were conducted on MEDLINE (accessed by PubMed). The reference list of the selected articles was also screened to find other relevant articles with an emphasis on ethical consideration in COVID-19 vaccine deployment and distribution. Results: Most developing countries are likely to face shortage and consequent uncertainty over timely COVID-19 vaccine availability. Developing countries are also at risk of significant preexisting vaccine hesitancy and also compromising justice because of the socioeconomic divide, enabling the rich to access retail vaccines before the poor. Finally, the recommended measures for implementing a mandatory vaccination policy are mostly devoid of feasibility in the global south. We identified ethical challenges and their feasibility of resolution by establishing ethically valid mechanisms for allocation and distribution of COVID-19 vaccine as a scarce resource in these resource-constrained settings. Ethical frameworks for assessing government measures towards vaccinating their respective populations are limited in their scope due to scientific uncertainty with regards to the timeliness of vaccine availability and the unpredictable frequency and severity of vaccine-related adverse effects. Conclusion: governments may escape moral culpability despite failing to ensure adequacy and timeliness of vaccination coverage in the absence of specific and measurable ethical benchmarks developed as part of a robust ethical framework.

Introduction: The rampant widespread of COVID-19 crossing continents in the year 2020 is primarily because of its unique spike protein architecture. Hence, the spike protein sequence similarities among the representatives of coronaviruses were evaluated so as to arrive at possible conservancy in its epitopes. Methods: Multiple sequence alignment and molecular phylogenetic analysis were done using MEGA software version X. Clustal omega open software was adapted to develop Percent Identity Matrix of spike proteins. Online IEDB tools were used to explore linear epitopes within the RBD region of spike protein of SARS CoV2 isolate of Wuhan-Hu-1 and their conservancy across the species of the chosen CoVs. Results: The constructed phylogenetic tree showed a primary cluster between SARS CoV2s of Wuhan and Bangladesh strains. The branch length of this primary cluster reflected their recency in emergence. Further, this primary cluster developed as an offshoot of yet another primary cluster between SARS CoV and bat SARS CoV. All betacoronaviruses grouped as one tertiary cluster, wherein MERS CoV formed as an independent offshoot and its branch length reflected that it is phylogenetically older. Both SARS CoV2s are the closest relatives to SARS CoV and Bat SARS CoV of China, and hence the similar pattern was confirmed through MEGA analysis. Ten linear epitopes were identified within the RBD region of the spike protein for the population of the State of Andhra Pradesh among Indian Asians based on their HLA haplotype diversity. Further, Conservancy Analysis of spike protein suggested that SARS CoV2 and SARS CoV shared 53% predicted epitopes. The physicochemical features of the envisaged polytope indicated the presence of 12. 96% charged residues with instability index showing stable nature and more hydrophilicity as revealed through GRAVY values indicating that residues of polytope possibly interact well in aqueous environment. The secondary structure of the envisaged polytope showed predominantly coils, moderate number beta pleated sheets and α-helices with 41. 2% residues in favoured region and 44. 7% in allowed regions of Ramachandran Plot. Conclusion: The derived predicted scores of T-cell and B-cell immunogenicity, MHC class I binding, non-toxic and non-allergic due to the identified multi-epitope confirmed to be antigenic and elicit both T-cell and B-cell immune responses. Population coverage tool (IEDB) showed an adequate fraction of individuals predicted to respond to a given set of identified epitopes with known MHC restrictions in Indian Asian population.

Introduction: The development of a vaccine against Staphylococcus aureus has proven to be much more difficult than expected. In this study, we considered and analyzed a mutant Toxic Shock Syndrome Toxin-1 (TSST-1) as a potential vaccine candidate. Methods: An NCBI sequence of TSST-1 was analyzed bioinformatically by online tools such as Ensemble and Pubmlst. The protein sequence of TSST-1 was similarly analysed by Expasy ProtParam, Phyre2 and Vaxign databases. The protein functional class was predicted by VICMpred database while the B-and T-cell epitopes were predicted by IEDB and BepiPred tools. The 3D structure was predicted by LOMETS, QMEAN, ProSA-web and ElliPro. The conservation of the epitopes was evaluated by ConSurf tool. Results: In silico analyses showed that this protein is present in high-prevalence sequence types of circulating clinical strains. It appears that TSST-1 has conserved liner and conformational B-cell epitopes. In addition, there are four potent of T-cell epitopes in this protein. Conclusion: This in silico data indicated that TSST-1 (and especially amino acid residues 81-221) is a promising vaccine target against S. aureus.

Introduction: Despite conization, high-grade squamous intraepithelial lesion can recur. Persistent human papilloma virus infection is an important factor of recurrence. We analyse different situations that could favor the persistence of this infection. Methods: A retrospective case-control study of 256 patients who underwent conization between 2015 and 2020 was conducted. Depending on positive or negative result of HPV test after the first 6 months post conization, two groups were defined and compared: 1) control group HPV-negative patients, 2) case group HPV-positive patients. Age, parity, smoking habit, menopause, body mass index (BMI), vaccination, HPV genotypes and exo and endocervical margin status were analysed. Results: 63 of the 256 patients studied, (24. 6%) persisted positive for HPV after conization, while 193 (75. 4%) became negative for HPV. Patients over 35 years old had a significantly higher risk of persistence of HPV after conization (OR 1. 9). Being menopausal was also significantly associated with the persistence of HPV (OR 2. 5). The presence of affected resection margins in cone specimen proved to be a risk factor for the persistence of HPV (OR 2. 3). The coexistence of multiple HPV genotypes before conization seemed to be a protective factor for HPV persistence (OR 0. 3). The rest of clinical characteristics studied failed to demonstrate statistical significance; therefore, it was not possible to classify them as risk and/or protective factors. Conclusions: Age over 35, menopause and affected resection margins of conization were significantly associated (p< 0. 05) with the persistence of HPV infection; however, HPV vaccination was not among the risk factors.

Introduction: Flagellin (FliC) is an essential and universal subunit of flagella in motile bacteria. Analysis of the sequence diversity of the FliC protein in the Enterobacteriaceae family may provide insight into the pathogenic strategy of these bacteria in the context of interaction with pathogen-associated molecular patterns (PAMPs). In addition, the efficacy of FliC as an adjuvant or a component of the multi-epitope vaccine has been demonstrated. Methods: We analyzed 392 full-length and non-redundant FliC proteins from the Enterobacteriaceae family. In the first step, isoelectric pH, molecular weight (kDa), and amino acid composition of FliC protein sequences were calculated using the ProtParam program. Next, the tertiary structure of the FliC proteins and its interaction with zebrafish TLR-5 was performed. Sequence alignments were performed using ClustalW software and the curricular phylogenetic tree was depicted using MEGA-7 software and iTOL web server. Finally, we evaluated the interaction of FliC proteins of Enterobacteriaceae family with TLR-5 to find the strongest docking. Results: Physicochemical properties and multiple sequence alignments revealed that FliC has a unique characterization in each genus. However, D1 as the binding domain site associated with TLR-5 exhibited high sequence conservation and the FliC protein of S. enterica subsp. enterica had the strongest interaction with TLR-5. Conclusions: FliC protein of S. enterica subsp. enterica can be consider as a promising epitope-delivery platform. In addition, phylogenetic analysis revealed that FliC may be acceptable marker for distinguishing genera in the family Enterobacteriaceae.

Introduction: Isolation of antibodies from the egg yolk of chickens is of particular interest as a source of specific antibodies for oral administration to prevent infections and use them as immunodiagnostic reagents. This study assessed the hypothesis that immunization with human immunodeficiency virus 1(HIV-1) viral peptides could induce a potent immune response that could be evaluated in chicken eggs. Methods: Nine healthy brown Leghorn layer hens (3 per HIV immunogen), aged 7 months, were immunized intramuscularly at multiple sites on the breast with specific KLH-conjugated HIV peptide candidate vaccines. The anti-HIV antibody response was measured using ELISA. Chicks were fed HIV hyper-immune eggs and their blood was collected for testing for anti-anti-idiotypic antibodies that neutralize the original HIV antigen using an inhibition ELISA. Results: The immunogenicity results showed that HIV peptide vaccines effectively produced strong anti-HIV immune responses in immunized brown Leghorn layer hens. The binding inhibition assay showed that 13. 9%– 20. 3% inhibition of the binding of avian anti-HIV gp 41 (fragment 579-601) or anti-HIV-gp120 antibodies (Ab-1) to immobilized HIVgp41, HIVgp120 peptide by anti-HIV gp 41 (fragment 579-601) or anti-HIV gp120 (fragments 308-331 or 421-438) antibodies present in serum sample replicates of chicks tested, suggesting that the chicks anti-HIV gp 41 (fragment 579-601) or anti-HIV-gp120 antibodies (fragments 308-331 or 421-438) were anti-antiidiotypic antibodies. This inhibition was not observed in the sera of chicks that were not fed with the hyperimmune eggs. Conclusion: Feeding chicks with hyperimmune eggs could potentially stimulate the production of anti-anti-idiotypic antibodies that can neutralize the original HIV antigen (gp120 or gp41). This could be an avenue for immunotherapy to improve the fight against HIV infections. However, more studies and clinical trials are required to demonstrate similar human immune responses.

Vaccines are a major weapon to control the present COVID-19 pandemic. To achieve this goal, vaccines should confer a robust and long-lasting immunity against SARS-Cov-2. Breakthrough infections and waning immunity are currently observed in patients that recovered from COVID-19 as well as in the vaccinated people. Therefore, a highly effective vaccine is needed to control the present and future outbreaks. Exogenous Nacetyl-5-methoxy-tryptamine or melatonin (MLT) is well known to potentiate an effective and equilibrated immune response in a variety of situation including viral and bacterial infections and vaccines against different microbial and cancer antigens. In regard to anti-SARS-Cov-2 vaccines, beside stimulating specific IgG production as well as specific CD4+ and CD8+ T cells, exogenous MLT might also enhance specific IgA and secretory IgA in the mucosae; hence, preventing the re-infection and/or asymptomatic transmission of the virus. Thus, a study is urgently proposed to evaluate the effects of MLT administration either before or after vaccination against SARS-Cov-2 to evaluate its effect on strength, quality and duration of the immunity. Las but not least, due to its powerful antioxidant and anti-inflammatory properties, MLT administration might minimize the occurrence of adverse events after the vaccination.

Introduction: Vaccination is the most effective measure to prevent Rotavirus infection in children under five years of age. The most important targets of neutralizing and protective antibodies against this virus are VP4 and VP7 proteins of Rotavirus. Today, the recombinant protein produced in yeast plays an important role in producing highly effective and cost-effective vaccines. Methods: The effect of different linkers, including flexible and rigid, were evaluated on the stability and immunogenicity of the protein via in silico assays. A suitable linker was selected and expressed in Pichia pastoris yeast. Prediction and validation were carried out using bioinformatics tools, including Expasy's ProtPara, Phyre2 online server, I-TASSER server, ElliPro. Moreover, an appropriate linker was selected for cloning into pPICZα and expression in P. pastoris. Results: The results showed that as a flexible linker, (GGGGS)3 was the best structure to provide stability for VP4-VP7 target fusion protein. The produced recombinant protein was stable after the expression. Conclusion: These in silico results and expression data on P. pastoris suggested that VP4– (GGGGS)3-VP7 construct can potentially serve as a potent immunogenic candidate for recombinant Rotavirus vaccines.