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1.
Background
Influenza virus infections are responsible for significant morbidity worldwide and therefore it remains a high priority to develop more broadly protective vaccines. Adjuvation of current seasonal influenza vaccines has the potential to achieve this goal.Methods
To assess the immune potentiating properties of Matrix-M?, mice were immunized with virosomal trivalent seasonal vaccine adjuvated with Matrix-M?. Serum samples were isolated to determine the hemagglutination inhibiting (HAI) antibody titers against vaccine homologous and heterologous strains. Furthermore, we assess whether adjuvation with Matrix-M? broadens the protective efficacy of the virosomal trivalent seasonal vaccine against vaccine homologous and heterologous influenza viruses.Results
Matrix-M? adjuvation enhanced HAI antibody titers and protection against vaccine homologous strains. Interestingly, Matrix-M? adjuvation also resulted in HAI antibody titers against heterologous influenza B strains, but not against the tested influenza A strains. Even though the protection against heterologous influenza A was induced by the adjuvated vaccine, in the absence of HAI titers the protection was accompanied by severe clinical scores and body weight loss. In contrast, in the presence of heterologous HAI titers full protection against the heterologous influenza B strain without any disease symptoms was obtained.Conclusion
The results of this study emphasize the promising potential of a Matrix-M?-adjuvated seasonal trivalent virosomal influenza vaccine. Adjuvation of trivalent virosomal vaccine does not only enhance homologous protection, but in addition induces protection against heterologous strains and thus provides overall more potent and broad protective immunity.2.
Background
An influenza H3N2 epidemic occurred throughout Southern China in 2012.Methods
We analyzed the hemagglutinin (HA) and neuraminidase (NA) genes of influenza H3N2 strains isolated between 2011–2012 from Guangdong. Mutation sites, evolutionary selection, antigenic sites, and N-glycosylation within these strains were analyzed.Results
The 2011–2012 Guangdong strains contained the HA-A214S, HA-V239I, HA-N328S, NA-L81P, and NA-D93G mutations, similar to those seen in the A/ Perth/16/2009 influenza strain. The HA-NSS061–063 and NNS160–162 glycosylation sites were prevalent among the 2011–2012 Guangdong strains but the NA-NRS402–404 site was deleted. Antigenically, there was a four-fold difference between A/Perth/16/2009 -like strains and the 2011–2012 Guangdong strains.Conclusion
Antigenic drift of the H3N2 subtype contributed to the occurrence of the Southern China influenza epidemic of 2012.3.
Yahya Mohammadzadeh Narges Rasouli Mohammad Hasan Samiee Aref Nasim Sadat Seyed Tabib Asghar Abdoli Peyvand Biglari Maryam Saleh Mansoureh Tabatabaeian Masoumeh Tavassoti Kheiri Abbas Jamali 《Biotechnology letters》2016,38(8):1321-1329
Objectives
To enhance the efficiency of influenza virosome-mediated gene delivery by engineering this virosome.Results
A novel chimeric influenza virosome was constructed containing the glycoprotein of Vesicular stomatitis virus (VSV-G), along with its own hemagglutinin protein. To optimize the transfection efficiency of both chimeric and influenza cationic virosomes, HEK cells were transfected with plasmid DNA and virosomes and the transfection efficiency was assessed by FACS analysis. The chimeric virosome was significantly more efficient in mediating transfection for all amounts of DNA and virosomes compared to the influenza virosome.Conclusions
Chimeric influenza virosome, including VSV-G, is superior to the conventional influenza virosome for gene delivery.4.
Asghar Abdoli Hoorieh Soleimanjahi Abbas Jamali Parvaneh Mehrbod Shima Gholami Zahra Kianmehr Neda Feizi Maryam Saleh Fariborz Bahrami Talat Mokhtari-Azad Mohsen Abdoli Masoumeh Tavassoti Kheiri 《Biotechnology letters》2016,38(6):941-948
Objectives
To evaluate MDCK and MDCK-SIAT1 cell lines for their ability to produce the yield of influenza virus in different Multiplicities of Infection.Results
Yields obtained for influenza virus H1N1 grown in MDCK-SIAT1 cell was almost the same as MDCK; however, H3N2 virus grown in MDCK-SIAT1 had lower viral titers in comparison with MDCK cells. The optimized MOIs to infect the cells on plates and microcarrier were selected 0.01 and 0.1 for H1N1 and 0.001 and 0.01 for H3N2, respectively.Conclusions
MDCK-SIAT1 cells may be considered as an alternative mean to manufacture cell-based flu vaccine, especially for the human strains (H1N1), due to its antigenic stability and high titer of influenza virus production.5.
Zeinab Panahi Asghar Abdoli Ghasem Mosayebi Mehdi Mahdavi Fariborz Bahrami 《Biotechnology letters》2018,40(3):527-533
Objective
To evaluate the combined effects of CpG oligodeoxynucleotides (CpG-ODNs) adjuvant and subcutaneous injection route on efficacy of a HIV-1-tat DNA vaccine candidate using BALB/c mice as an animal model.Results
Evaluation of cellular and humoral immunity of mice injected subcutaneously with HIV-1-tat gene cloned into a pcDNA3.1 vector indicated that significant levels of IFN-γ cytokine secretion (900 pg/ml), lymphocyte proliferation (2.5 stimulation index) and IgG2a (1.45 absorbance 450 nm) production could be achieved. These indicators of stimulated cellular immunity were elicited 2 weeks after the last injection (P < 0.05).Conclusions
Formulation of HIV-1-tat DNA vaccine candidate with CpG-ODNs as an adjuvant while administrated subcutaneously are a promising approach to induce effective cellular immunity responses against HIV-1 infection.6.
Rongcheng Li Hanhua Fang Yanping Li Youping Liu Michele Pellegrini Audino Podda 《Immunity & ageing : I & A》2008,5(1):2
Background
The safety and immunogenicity of an MF59?-adjuvanted subunit influenza vaccine (Sub/MF59?; FLUAD®, Novartis Vaccines) was evaluated among elderly Chinese subjects (≥ 60 years of age). After a preliminary Phase I, open-label study (n = 25) to assess safety 1–14 days post-vaccination, a comparative observer-blind, randomised, controlled clinical trial (n = 600) was performed to assess safety and immunogenicity versus a non-adjuvanted subunit influenza vaccine (Subunit; Agrippal®, Novartis Vaccines). Subjects were randomised (2:1) to receive Sub/MF59? or Subunit.Results
Both vaccines were well tolerated, with no vaccine-related serious adverse events reported during the Phase I trial. During the observer-blind study, local and systemic reactions were generally similar for both vaccines 1–22 days post-vaccination; however, injection-site induration was more frequent among the Subunit group (P < 0.05), and mild pain at the injection site and fever were more frequent among Sub/MF59? recipients (P ≤ 0.005). Both vaccines induced a significant (P < 0.001) increase in geometric mean titres (GMTs) for the three strains tested, versus baseline; GMTs against A/H1N1, A/H3N2 and B were significantly higher in the Sub/MF59? group (P = 0.034, P < 0.001 and P = 0.005, respectively). GMT ratios against A/H1N1, A/H3N2 and B were also significantly higher in the Sub/MF59? group (P = 0.038, P < 0.001 and P = 0.006, respectively). Similarly, the percentage of subjects achieving seroprotection or seroconversion on Day 22 was greater for Sub/MF59? recipients, reaching significance for A/H3N2 (P < 0.001).Conclusion
MF59?-adjuvanted subunit influenza vaccine is well tolerated by elderly Chinese subjects and induces a higher level of immunogenicity than a non-adjuvanted subunit influenza vaccine in this population that is at high risk of influenza-related complications.Clinical trial registry
http://www.clinicaltrials.gov, NCT003106487.
Arshid Yousefi-Avarvand Mohsen Tafaghodi Saman Soleimanpour Farzad Khademi 《生物学前沿》2018,13(4):293-296
Background
Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis (Mtb). This disease with two million deaths per year has the highest mortality rate among bacterial infections. The only available vaccine against TB is BCG vaccine. BCG is an effective vaccine against TB in childhood, however, due to some limitations, has not proper efficiency in adults. Also, BCG cannot produce an adequately protective response against reactivation of latent infections.Objective
In the present study we will review the most recent findings about contribution of HspX protein in the vaccines against tuberculosis.Methods
Therefore, many attempts have been made to improve BCG or to find its replacement. Most of the subunit vaccines for TB in various phases of clinical trials were constructed as prophylactic vaccines using Mtb proteins expressed in the replicating stage. These vaccines might prevent active TB but not reactivation of latent tuberculosis infection (LTBI). A literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of HspX protein in tuberculosis vaccines.Results
Ideal subunit post-exposure vaccines should target all forms of TB infection, including active symptomatic and dormant (latent) asymptomatic forms. Among these subunit vaccines, HspX is the most important latent phase antigen of M. tuberculosis with a strong immunological response. There are many studies that have evaluated the immunogenicity of this protein to improve TB vaccine.Conclusion
According to the studies, HspX protein is a good candidate for development of subunit vaccines against TB infection.8.
I. Djuric-Filipovic Marco Caminati D. Filipovic C. Salvottini Z. Zivkovic 《Clinical and molecular allergy : CMA》2017,15(1):7
Background
Allergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy).Methods
7–18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up.Results
There was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation.Conclusions
Our data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.9.
Background
Nitrous oxide (N2O), a long-standing anesthetic, is also neurotoxic by interfering with the bioavailability of vitamin B12 if abused. A few case studies have reported the neurological and psychiatric complications of N2O.Case presentation
Here, we reported a patient of N2O induced subacute combined degeneration (SCD) with longitudinally extensive myelopathy with inverted V-sign exhibiting progressive limb paresthesia and unsteady gait.Conclusions
This case raises the awareness of an important mechanism of neural toxicity of N2O, and clinical physicians should be well recognized this in the field of substance-related disorders.10.
Louis Fries Vivek Shinde Jeffrey J. Stoddard D. Nigel Thomas Eloi Kpamegan Hanxin Lu Gale Smith Somia P. Hickman Pedro Piedra Gregory M. Glenn 《Immunity & ageing : I & A》2017,14(1):8
Background
A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study.Results
A total of 220 healthy males and females?≥?60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine.Conclusions
RSV F protein nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.11.
12.
Janardhanraj Subburaj Akshay Datey Jagadeesh Gopalan Dipshikha Chakravortty 《Journal of biological engineering》2017,11(1):48
Background
Needle-free, painless and localized drug delivery has been a coveted technology in the area of biomedical research. We present an innovative way of trans-dermal vaccine delivery using a miniature detonation-driven shock tube device. This device utilizes~2.5 bar of in situ generated oxyhydrogen mixture to produce a strong shockwave that accelerates liquid jets to velocities of about 94 m/s.Method
Oxyhydrogen driven shock tube was optimized for efficiently delivering vaccines in the intradermal region in vivo. Efficiency of vaccination was evaluated by pathogen challenge and host immune response. Expression levels of molecular markers were checked by qRT-PCR.Results
High efficiency vaccination was achieved using the device. Post pathogen challenge with Mycobacterium tuberculosis, 100% survival was observed in vaccinated animals. Immune response to vaccination was significantly higher in the animals vaccinated using the device as compared to conventional route of vaccination.Conclusion
A novel device was developed and optimized for intra dermal vaccine delivery in murine model. Conventional as well in-house developed vaccine strains were used to test the system. It was found that the vaccine delivery and immune response was at par with the conventional routes of vaccination. Thus, the device reported can be used for delivering live attenuated vaccines in the future.13.
Background
Influenza vaccination coverage remains low among health care workers (HCWs) in many health facilities. This study describes the social network defined by HCWs’ conversations around an influenza vaccination campaign in order to describe the role played by vaccination behavior and other HCW characteristics in the configuration of the links among subjects.Methods
This study used cross-sectional data from 235 HCWs interviewed after the 2010/2011 influenza vaccination campaign at the Hospital Clinic of Barcelona (HCB), Spain. The study asked: “Who did you talk to or share some activity with respect to the seasonal vaccination campaign?” Variables studied included sociodemographic characteristics and reported conversations among HCWs during the influenza campaign. Exponential random graph models (ERGM) were used to assess the role of shared characteristics (homophily) and individual characteristics in the social network around the influenza vaccination campaign.Results
Links were more likely between HCWs who shared the same professional category (OR 3.13, 95% CI?=?2.61–3.75), sex (OR 1.34, 95% CI?=?1.09–1.62), age (OR 0.7, 95% CI?=?0.63–0.78 per decade of difference), and department (OR 11.35, 95% CI?=?8.17–15.64), but not between HCWs who shared the same vaccination behavior (OR 1.02, 95% CI?=?0.86–1.22). Older (OR 1.26, 95% CI?=?1.14–1.39 per extra decade of HCW) and vaccinated (OR 1.32, 95% CI?=?1.09–1.62) HCWs were more likely to be named.Conclusions
This study finds that there is no homophily by vaccination status in whom HCWs speak to or interact with about a workplace vaccination promotion campaign. This result highlights the relevance of social network analysis in the planning of health promotion interventions.14.
Background
Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.Methods
Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice.Results
A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response.Conclusions
Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.15.
Objective
To investigate the relationship between the response to influenza vaccination and the ability to produce proinflamatory cytokines in elderly subjects.Methods
Whole blood samples from 25 elderly subjects collected before influenza vaccination were stimulated with the influenza vaccine in order to evaluate the secretion of five specific cytokines: TNFα, IFNα, IFNγ, IL2 and IL10. The results were correlated with the increased HAI antibody titres two weeks after vaccination.Results
Only 30% of elderly individuals seroconverted after vaccination. Although 50 to 70% of the cohort did not produce TNFα, IFNα, IFNγ, IL2 or IL10, all of the individuals who seroconverted were able to produceTNFα. Furthermore production of IFNγ, with or without production of IFNα/β, was not associated with a better response to the vaccine.Conclusion
Production of TNFα appears to be primordial for an efficient vaccine response, and may provide a predictive marker for the humoral response to vaccination. It may also provide the basis for evaluating agents designed to rescue TNFα-producing cells. This study emphasises a need to rescue TNF-producing cell function.16.
Background
The influenza matrix protein (M1) layer under the viral membrane plays multiple roles in virus assembly and infection. N-domain and C-domain are connected by a loop region, which consists of conserved RQMV motif.Methods
The function of the highly conserve RQMV motif in the influenza virus life cycle was investigated by site-directed mutagenesis and by rescuing mutant viruses by reverse genetics. Co-localization of M1 with nucleoprotein (NP), clustered mitochondria homolog protein (CLUH), chromosome region maintenance 1 protein (CRM1), or plasma membrane were studied by confocal microscopy.Results
Mutant viruses containing an alanine substitution of R163, Q164 and V166 result in the production of the virus indistinguishable from the wild type phenotype. Single M165A substitution was lethal for rescuing infection virus and had a striking effect on the distribution of M1 and NP proteins. We have observed statistically significant reduction in distribution of both M165A (p?0,05) and NP (p?0,001) proteins to the nucleus in the cells transfected with the reverse –genetic system with mutated M1. M165A protein was co-localized with CLUH protein in the cytoplasm and around the nucleus but transport of M165-CLUH complex through the nuclear membrane was restricted.Conclusions
Our finding suggest that methionine 165 is essential for virus replication and RQMV motif is involved in the nuclear import of viral proteins.17.
Li Sun Quan Yuan Tianhua Xu Li Yao Jiangmin Feng Jianfei Ma Lining Wang Changlong Lv Danan Wang 《Biotechnology letters》2017,39(8):1159-1166
Objectives
To investigate the potential of interleukin (IL)-15 as a novel adjuvant for Mycobacterium tuberculosis (Mtb) antigen 85A (Ag85A) vaccine.Results
C57BL/6 mice were intramuscularly immunized three times with a plasmid expressing the Ag85A-IL-15 fusion protein (pcDNA3.1-Ag85A-IL-15), with the empty pcDNA3.1 vector and the pcDNA3.1-Ag85A as control. Mice vaccinated with pcDNA3.1-Ag85A-IL-15 generated more secretory IgA (sIgA) into their lung (209 ± 21 μg/ml) and acquired an enhanced serum IgG response to Ag85A. IgG2a/IgG1 ratios were upregulated, natural killer cell activity was augmented and Ag85A-specific splenic T cell proliferation was enhanced in these mice as well. Vaccination with pcDNA3.1-Ag85A-IL-15 promoted the polarization of CD4+ T cells towards a Th1 type in the spleen, and significantly upregulated the serum level of interferon (IFN)-γ (458 ± 98 pg/ml), a typical Th1 cytokine. IFN-γ-expressing CD8+ cells were also increased in the spleen after pcDNA3.1-Ag85A-IL-15 immunization.Conclusions
A superior immune type I response in mice vaccinated with plasmid Ag85A-IL-15 has been achieved.18.
Background
The age-related weakening of the immune system makes elderly subjects less responsive to influenza vaccination. In the last years, two “enhanced vaccines” were licensed for individuals aged ≥65 years, one being a subunit vaccine (Fluad®) containing the MF59 adjuvant administered intramuscularly (IM-MF59) and the other one a split non-adjuvanted vaccine administered intradermally (Intanza® 15mcg) (ID). In the present study, we evaluated and compared the antibody responses against the three vaccine antigens and heterovariant A(H3N2) circulating viruses induced by IM-MF59 and ID influenza vaccines in 80 elderly institutionalized volunteers (40 per group) during the Winter season 2011–2012.Results
Hemagglutination inhibiting (HI) antibody titers were assessed in blood samples collected before, 1 and 6 months after vaccination. One month after vaccination both the IM-MF59 and ID vaccines induced increases in HI titers against all the three vaccine strains. The results in the two groups were similar against the A(H3N2) and A(H1N1) strains. Responses against the B strain typically tended to be higher after ID than IM-MF59, yet both vaccines stimulated lower responses against the B strain than against the two A strains. The two vaccines induced favorable results also against four epidemic drifted A(H3N2) viruses circulating in Winter 2011–2012. Six months after vaccination, the HI titers decreased in both groups.Conclusion
The responses induced by IM-MF59 and ID vaccines in institutionalized elderly people were similar against the A(H3N2) and A(H1N1) strains but frequently higher, for the ID, against the B strain. The two vaccines induced positive responses against drifted A(H3N2) circulating viruses.19.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.20.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16