Vaccine Research
Volume:8 Issue: 1, Winter and Spring 2021

To understand the effects of COVID-19 vaccines it would be essential to have knowledge about the effects of the disease during the time that vaccines were unavailable. Hence, we tracked the clinical outcomes of Iranian COVID-19 patients during Feb 19th till May 1st 2020 by a longitudinal follow-up study of patients discharged from a university hospital in Iran.

Demographic, clinical, and paraclinical data (chest CT scan imaging, and RT-PCR tests) of 139 patients were collected at the admission time. Preliminary clinical, radiological, laboratory, treatment information, and follow up results were extracted and collected from patients' records.

The mean age of the patients was 60.56±16.32 years. The most common symptoms on admission were dyspnea (79.1%), coughing (77.3%) and fever (73.1%). The common radiological pattern was multifocal patchy ground-glass infiltration. The patients were followed-up for 8 weeks by phone call. During discharge, 24.8% of the patients had no symptoms, the common residue symptoms were weakness and malaise (48.2%), dyspnea (38.7%), coughing (20.4%), hyposmia (18.5%). On week 8, 74.6% of the patients had no symptom. Moreover, 47.14% of CT scan results improved after 4 weeks and 43.39% after 8 weeks.

Further follow-up studies are required to determine other detrimental illnesses related to the disease and how vaccination against COVID-19 can affect them.

The tick-borne encephalitis (TBE) virus causes a dangerous neuroinfection in humans can serve as a model for studying the mechanisms of interaction of pathogens with specific antibodies during active and passive immunization. Several commercial vaccines are currently used against TBE. This review analyzes long-term studies aimed at explaining the active and passive efficacy of specific immunoprophylaxis against TBE.

The effectiveness of "Encepur® adult" TBE vaccine has been studied in terms of seroconversion and strength of the immune response by serological reactions, namely IFA, ELISA and neutralizing were reviewed.

Rapid elimination of the virus (after 1-2 days) can occur in vaccinated individuals with antibodies in titers of more than 1: 400. Persons with antibodies in titers of 1: 100 and 1: 200, most likely, should be offered mandatory revaccination. It should also take into account the duration of the retention of post-vaccination antibodies.

In the year of TBE vaccination, the immune response was at a high level and practically did not differ. A particularly high level of immune protection was observed in persons who were vaccinated by a combination of TBE vaccines of various producers.

Shigellosis is a form of acute intestinal infection and one of the global health problems that occur in human by pathogenic species of Shigella. Producing a cost-effective and protective vaccine against the pathogenic strains of these bacteria will have a significant effect on the improvement of public health. The purpose of this research was to design, express and purify a multiepitope protein as a candidate vaccine against Shigella pathogenic species.

The multi-epitope protein-encoding Ipas, Omps and IcsA genes was designed based on previous bioinformatics assessments and synthesized in pET28a (+) expression vector. Since no detectable expression was observed, the gene was subcloned into pET32a (+). The pET32a (+) recombinant vector containing the desired gene was transferred into Escherichia coli BL21 (DE3) and the expression of the recombinant protein was induced using IPTG. The protein was purified using a nickel column. Finally, the Western blotting method was used to confirm the expression of the recombinant protein.

The sub-cloning of the gene was confirmed using PCR reaction. Gene expression analysis showed that the desired protein had a suitable expression. Western blotting analysis confirmed the expression of the recombinant protein.

The expressed and purified multi-epitope recombinant protein, containing the main epitopes of the common antigens of pathogenic Shigella species could be achieved as the first step to design a multiepitope vaccine candidate against shigellosis.

A modified Susceptible - Exposed - Infected - Quarantined - Recovered (SEIQR) epidemic model with vaccination is considered to understand the transmission dynamics of Ebola disease.

The impact of vaccination as a control strategy is investigated in two cases: vaccination is a constant function of time and time - dependent vaccination. For the first case, the reproduction number R0 is derived and mathematical analysis reveals that the existence of equilibrium points and the qualitative properties of solutions of the resulting autonomous model are completely determined by R0. For the second case, we conduct an analysis that is based on optimal control theory to determine optimal application of vaccination control.

It is shown that the disease - free equilibrium is locally asymptotically stable if R0 < 1 and unstable if R0 > 1 . When  R0 > 1, the disease - free equilibrium loses its stability and an endemic equilibrium point that is locally asymptotically stable emerges as also verified by demonstrating the existence of forward bifurcation at R0 = 1 using the method by Castillo - Chavez and Song. Optimal control analysis shows that that vaccination effort is affected by the cost associated with it. Vaccination control of Ebola can be carried out at maximum rate from the onset of the outbreak if it is not costly.

Vaccination is an important intervention strategy in controlling Ebola outbreaks.

Many countries are presently concerned about providing a safe vaccine with minimal side-effects against COVID 19. Here, we aimed to develop a multiepitope vaccine by utilization of spike, envelope, nucleocapsid and membrane proteins of SARS-CoV-2 virus.

Online servers were employed for forecasting the most robust B-cell, T-cell and IFN-γ epitopes to stimulate the immune system. Then the top selected epitopes alongside the sequence of Heparin-Binding Hemagglutinin Adhesin (HBHA) protein were applied to design a novel multiepitope vaccine, bioinformatically. The physicochemical characteristics and the protein structures of the proposed vaccine were defined using online tools. The docking process between Toll-like Receptor 4/Myeloid Differentiation Factor 2 (TLR4/MD2 receptor) and the designed recombinant structure was also investigated.

The designed construct had -0.210 GRAVY and 36.39 instability indices which make it theoretically stable. The designed construct was predicted to be soluble and non-allergenic. The approximate half-life of the proposed structure was computed 30 hours in mammalian reticulocytes and more than 10 hours in Escherichia coli. In its tertiary structure, 93% of the residues were in the core region and had a score of 52.73 for 3D verification and -5.55 for Z-score. Protein-protein docking of HBHA and TLR4/MD2 receptor was successful with the lowest energy of -1310.6 kcal/mol.

The bioinformatics evaluations indicate that the designed structure is stable and immunogenic for development of a protein-based subunit vaccine against COVID-19.

Peste des petits ruminants (PPR) or goat plague is a highly contagious viral disease of small ruminants such as sheep and goats with 90% and 100% morbidity and mortality, respectively. This study was aimed at assessing Peste des petits Ruminants Virus (PPRV) specific antibodies in vaccinated pregnant ewes and subsequently the passive immunity in their lambs.

Seventeen apparently healthy sheep (8 pregnant and 9 non pregnant), 2-3 years old and kept under semi-intensive system of management were used. Ewes were vaccinated with the National Veterinary Research Institute PPR vaccine Nigeria strain 75/1 with a virus titre of 103 Tissue Culture Infectious Dose (TCID). Serum Samples were collected from all the sheep before and after vaccination at interval of two weeks for a period of seven months. The resultant (8) lambs were given birth to, blood sample were collected for four month and sera samples were examined using Competitive ELISA (c-ELISA) for the presence of specific PPR-N antibodies. 

The analysed result showed that there was significant difference      (P < 0.05) in the mean PPRV-N specific antibody c-ELISA values (0-13) before vaccination and the percentage competition protective values (> 50%). However, no significant difference (p > 0.05) post-vaccination in both pregnant and non-pregnant ewes was observed throughout the period of the study with mean PPRV-N specific c-ELISA antibodies of 72-86 and 52-86, respectively. The mean PPRV-N specific antibodies values were maintained within the protective value (> 50 %). The result of this study also showed that there was significant difference (P < 0.05) with mean PPRV-N specific c-ELISA antibodies (17.3-29.4; 87.5%) of lambs born to vaccinated pregnant Yankassa ewes from 8 weeks.

This study showed that vaccination does not affect pregnancy with Nigeria 75/1 strain of PPR vaccine in ewes as there was no record of abortion. There was a rapid PPR maternal antibody decay in lambs from the 8th week of age as it was observed that at age 10 weeks, only 37.5 % of the lambs had protective titre. It is therefore recommended that lambs can be vaccinated at 9th week to avoid the window of susceptibility to PPR virus infection.

Hepatitis B Vaccine (HBV) is a safe and effective vaccine that is nowadays recommended for all infants at birth as well as adults who could be exposed to hepatitis B virus. HBV can provide lifetime protection against hepatitis B virus infection. Despite its highly effective disease prevention, HBV can also cause adverse effects for the vaccinated population. A vast majority of Iran's population are vaccinated with recombinant hepatitis B vaccine (rHBV) which is manufactured by the Production and Research Complex of Pasteur Institute of Iran.

  The reported adverse events of rHBV, obtained from Diseases Management Center of Iran’s Ministry of Health were compared with those in The Vaccine Adverse Event Reporting System (VAERS, a United States program for vaccine safety, co-managed by the U.S. Centers for Disease Control and Prevention) during 2015 to 2017.

The most common adverse events after administration of rHBV, manufactured by Pasteur Institute of Iran was injection site reactions and no life threatening adverse event was observed.

Despite reports by VAERS indicating that HBV can cause adverse events and even death in the United States, no such adverse effects were observed in rHBV manufactured in Iran.

Cervical cancer is the fourth leading cause of cancer death in women worldwide. Nearly all cervical cancers are resulted from high-risk Human Papillomavirus (HPV) infection. Currently, there is no available HPV-specific therapy. Cancer therapeutic vaccines have shown anti-tumor efficacy in preclinical animal models as well as clinical patients.

Here, we used a previously-reported therapeutic vaccine candidate (VR111) based on HPV16E7-HBcAg-Hsp65 fusion protein (with aluminum hydroxide adjuvant) and injected mice with 2 doses of VR111 at a two-week interval 2 days after TC-1 tumor cell implantation. Tumor growth and animal survival rates were monitored and the vaccine-associated immune responses were evaluated by cytotoxic T lymphocytes assay, T-cell proliferation assay and CD4+/CD8+ T-cell depletion.

In TC-1 tumor murine model, VR111 vaccine showed potent dose dependent therapeutic efficacy against tumor growth and improved survival rates in the medium (10 μg) and high doses (30 μg). The three fusion components of VR111 were all necessary to induce the best anti-tumor activity, CTL response and T cell proliferation. The tumor growth inhibition and a higher mouse survival rate were among the beneficial effects of cisplatin-based combination treatment. Moreover, the anti-tumor potency of VR111 vaccine was proved to be significantly associated with E7 specific CD8+ T cell immune response and the adoptive lymphocyte transfer therapy also showed tumor growth inhibition.

The results confirmed VR111 as a potent therapeutic HPV vaccine candidate with superior anti-tumor efficacy in a murine model of HPV-induced cancer which its potentials could be considered for combination therapies against cervical cancer.

Although, conventional methods for the expression of polyomaviruses and herpesviruses recombinant proteins for serological  assays  and  vaccine  developments  in baculoviruses are well established, the manipulations are laborious and time consuming.

A new expression system based on plasmid was used to express two polyomaviruses major capsid protein VP1 (JCV VP1 and BKV VP1), and two herpesviruses glycoproteins (HSV-1 gD and VZV gE) in insect cells. A ligation independent cloning (LIC) was applied to generate the recombinant plasmids. Transfection of Sf9 insect cells were performed using the recombinants. The produced proteins were analysed using SDS-PAGE, immunofluorescence, and immunoblotting.

JCV-VP1, BKV-VP1, VZV-gE and HSV-1gD were successfully expressed in the insect cells, 48 h post-infection and detected in cytoplasm and cell membranes with immunoreactivity. This plasmid based expression system took 5 days to express the protein.

The plasmid based expression system in insect cells was highly efficient and would be ideal for rapid expression of polyomaviruses and herpesviruses proteins in insect cells to be potentially used in applications such as vaccine components and serological assays.

Vaccine safety surveillance is important to identify and manage adverse events following immunisation (AEFI) and avoid vaccine hesitancy. Currently, COVID-19 vaccines are administered to large numbers of people to try and curb the pandemic. In this paper, quantitative methods for causality assessment of AEFI are described. Qualitative methods for causality assessment involve an expert panel reviewing each AEFI report to determine whether the AEFI can be attributed to the vaccine. Each AEFI is determined to be classified as consistent, inconsistent, indeterminate or unclassifiable in terms of causality. Quantitative approaches can strengthen causality assessment outcomes. However, the potential for bias and errors should be considered for each safety signal identified. Vaccine and population specific factors may affect AEFI incidence, with a need to obtain background rates to frame safety signals identified into the local context. Several case scenarios from the vaccine safety surveillance in Brunei are used to illustrate the practical application of quantitative approaches for AEFI causality assessment (including comparison of AESI incidence to background rates and disproportionality analysis), which complement the traditional qualitative methods.

Fowl adenoviruses (FAdV) cause inclusion body hepatitis (IBH) in chickens and new vaccination strategies against IBH are needed as an effective control measure in the poultry industry.

The attenuated FAdV isolates from from chicken embryonated (UPM1137E20) and cell culture (UPM1137CEL35) were evaluated and compared based on sequence analysis of hexon and fiber genes. Their pathogenicities and immunogenicities were then determined in the commercial broiler chickens. Groups of chicken were inoculated with 0.5ml chicken-embryonated-derived attenuated FAdV isolates via oral and IP routes and sera, trachea, liver and gizzard samples were collected at days 3, 7, 14 and 21post-inoculation.

Molecular analysis revealed both isolates had 99.1% and 97.3% homologies in the L1 loop region of hexon gene and knob region of fiber gene, respectively. Molecular changes in UPM1137E20 were prominent in the knob of fiber gens with 3 amino acid changes, while for UPM1137CEL35, notable in the L1 loop region with 3 amino acid changes. It was demonstrated that both attenuated isolates are non-pathogenic and safe in commercial broiler chickens. Neither gross nor histopathological lesions were recorded in all tested groups. Both isolates induced high antibody response significantly via intraperitoneal route when compared to the control.

  UPM1137E20 isolate had a high potential to be further evaluated as a live attenuated vaccine against viral poultry diseases such as IBH.

Recently the term vaccine-induced immune thrombotic thrombocytopenia (VITT) used for individual which have thrombotic phenomena followed by ChAdOx1 nCoV-19 vaccine (AstraZeneca) administration against SARS coronavirus. Here we report the 27 years old healthy male and known case of G6PD deficiency which come to emergency department with progressive right calf swallow from 12 days ago and hemoptysis from a day ago. he mentioned he had administrated First dose of AstraZeneca vaccine for 3 weeks ago. He admitted with suspected pulmonary thromboembolism (PTE) followed by Deep vein thrombosis (DVT). In color Doppler study there are dilation in right calf vain with elevated lab measurement d-dimer indicated DVT also in computed tomography angiography (CTA) there are some evidence of filling defect in left pulmonary branch and right inferior lobar artery which represent to PTE.

Decades after the production of recombinant vaccines, the production of large scale and commercial use of such vaccines has become an important issue in the academic community. Newcastle disease is an infectious and highly contagious viral disease that causes diseases with different virulence and high infectivity in birds, especially chickens. Newcastle disease imposes severe economic losses on the poultry industry, and as a result, tackling it is always a priority for all countries of the world. In this regard, many vaccines have been produced, some of which are commercialized and some of which are in the testing phase. Given the economic importance of controlling Newcastle disease, the production of recombinant vaccines against the disease has been one of the hottest areas in the history of recombinant vaccines. Over the past three decades, many laboratory studies have been conducted to produce recombinant Newcastle disease vaccines on various platforms, which in many cases have yielded promising results. This article reviews the literature on the production of recombinant Newcastle disease vaccines. In this regard, while introducing Newcastle disease and its causative agent, the basics of producing recombinant vaccines and production platforms are explained. The following are some studies that have shown promising results for the production of the recombinant Newcastle disease vaccine. At the end of this article, while summarizing, areas for future research are introduced.

Cutaneous reactions reported post COVID-19 trials range from acute and immediate to delayed reactions. The suspected trigger for hypersensitivity reactions is the inactive ingredients, such as polyethylene glycol in mRNA vaccines and polysorbate 80 in AstraZeneca. Localised or injection- site reactions are generally self-limiting and occur within seven days. Younger and female patients were more likely to report injection-site reactions, and most cutaneous reactions after the second dose occurred sooner than after the first dose. Delayed large local reactions or ‘COVID arm’ have been reported after seven days post vaccination and generally resolve within two weeks. However, there were cases reported four days post-AstraZeneca vaccination. Other dermatological reactions, such as pityriasis rosea- like eruptions and flares of existing cutaneous conditions were seen in mRNA and AstraZeneca recipients but not in Sinopharm. Risk stratifying vaccine recipients into low, medium or high risk of developing severe allergic reactions may be done using screening questions. Skin testing may be considered for the high risk category but negative skin testing does not rule out a subsequent allergic response. Delayed cutaneous reactions may be misdiagnosed as cellulitis and administered unnecessary antibiotics.

Rabies is almost always fatal but entirely preventable through proper vaccination. Inadequacy of costly high-quality cell culture vaccines is sometimes a bottleneck for expanded rabies control plans. Reverse genetics along with other molecular biology means are trying to improve the immunogenicity and yield of rabies vaccine products.

An additional glycoprotein gene of the rabies virus PV strain was inserted between the glycoprotein and polymerase genes of the virus. The viral proteins were expressed at the T7BHK cell line to rescue the recombinant virus.

The recombinant virus containing two consecutive glycoprotein genes was rescued from T7BHK cells. The virus particles were functional and successfully infected the permissive BSR cell line.

The new virus strain with an additive copy of the glycoprotein gene has a good potential to be utilized in different studies, including cell biology and immunological properties of the rabies virus. In this study, the recombinant rabies virus was successfully rescued from cell culture which would pave the way for further investigations on this virus.