scholarly journals Core-Proteomics-Based Annotation of Antigenic Targets and Reverse-Vaccinology-Assisted Design of Ensemble Immunogen against the Emerging Nosocomial Infection-Causing Bacterium Elizabethkingia meningoseptica

2021 ◽  
Vol 19 (1) ◽  
pp. 194
Author(s):  
Muhammad Idrees ◽  
Muhammad Yasir Noorani ◽  
Kalim Ullah Altaf ◽  
Eid A. Alatawi ◽  
Faris F. Aba Alkhayl ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Dynamic Properties ◽  
Dynamics Simulation ◽  
Strong Immune Response ◽  
Physiochemical Properties ◽  
Hospital Acquired Infection ◽  
Elizabethkingia Meningoseptica ◽  
Structural Vaccinology ◽  
Hospital Acquired

Elizabethkingia meningoseptica is a ubiquitous Gram-negative emerging pathogen that causes hospital-acquired infection in both immunocompromised and immunocompetent patients. It is a multi-drug-resistant bacterium; therefore, an effective subunit immunogenic candidate is of great interest to encounter the pathogenesis of this pathogen. A protein-wide annotation of immunogenic targets was performed to fast-track the vaccine development against this pathogen, and structural-vaccinology-assisted epitopes were predicted. Among the total proteins, only three, A0A1T3FLU2, A0A1T3INK9, and A0A1V3U124, were shortlisted, which are the essential vaccine targets and were subjected to immune epitope mapping. The linkers EAAK, AAY, and GPGPG were used to link CTL, HTL, and B-cell epitopes and an adjuvant was also added at the N-terminal to design a multi-epitope immunogenic construct (MEIC). The computationally predicted physiochemical properties of the ensemble immunogen reported a highly antigenic nature and produced multiple interactions with immune receptors. In addition, the molecular dynamics simulation confirmed stable binding and good dynamic properties. Furthermore, the computationally modeled immune response proposed that the immunogen triggered a strong immune response after several doses at different intervals. Neutralization of the antigen was observed on the 3rd day of injection. Conclusively, the immunogenic construct produces protection against Elizabethkingia meningoseptica; however, further immunological testing is needed to unveil its real efficacy.

scholarly journals Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1327
Author(s):  
Azaz Ul Haq ◽  
Abbas Khan ◽  
Jafar Khan ◽  
Shamaila Irum ◽  
Yasir Waheed ◽  
...  
Keyword(s):  
Immune Response ◽  
Yersinia Pestis ◽  
Vaccine Development ◽  
Dynamic Properties ◽  
Dynamics Simulation ◽  
Strong Immune Response ◽  
Agent Based ◽  
Aliphatic Index ◽  
Structural Vaccinology ◽  
Potential Vaccine

Yersinia pestis is responsible for plague and major pandemics in Asia and Europe. This bacterium has shown resistance to an array of drugs commonly used for the treatment of plague. Therefore, effective therapeutics measurements, such as designing a vaccine that can effectively and safely prevent Y. pestis infection, are of high interest. To fast-track vaccine development against Yersinia pestis, herein, proteome-wide vaccine target annotation was performed, and structural vaccinology-assisted epitopes were predicted. Among the total 3909 proteins, only 5 (rstB, YPO2385, hmuR, flaA1a, and psaB) were shortlisted as essential vaccine targets. These targets were then subjected to multi-epitope vaccine design using different linkers. EAAK, AAY, and GPGPG as linkers were used to link CTL, HTL, and B-cell epitopes, and an adjuvant (beta defensin) was also added at the N-terminal of the MEVC. Physiochemical characterization, such as determination of the instability index, theoretical pI, half-life, aliphatic index, stability profiling, antigenicity, allergenicity, and hydropathy of the ensemble, showed that the vaccine is highly stable, antigenic, and non-allergenic and produces multiple interactions with immune receptors upon docking. In addition, molecular dynamics simulation confirmed the stable binding and good dynamic properties of the vaccine–TLR complex. Furthermore, in silico and immune simulation of the developed MEVC for Y. pestis showed that the vaccine triggered strong immune response after several doses at different intervals. Neutralization of the antigen was observed at the third day of injection. Conclusively, the vaccine designed here for Y. pestis produces an immune response; however, further immunological testing is needed to unveil its real efficacy.

scholarly journals Recombinant Antigens Based on Non-Glycosylated Regions from RBD SARS-CoV-2 as Potential Vaccine Candidates against COVID-19

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 928
Author(s):  
Leandro Núñez-Muñoz ◽  
Gabriel Marcelino-Pérez ◽  
Berenice Calderón-Pérez ◽  
Miriam Pérez-Saldívar ◽  
Karla Acosta-Virgen ◽  
...  
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Polyclonal Antibodies ◽  
Igg Antibodies ◽  
Mice Model ◽  
Strong Immune Response ◽  
Recombinant Antigens ◽  
Glycosylation Sites ◽  
Potential Vaccine

The Receptor-Binding Domain (RBD) of the Spike (S) protein from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has glycosylation sites which can limit the production of reliable antigens expressed in prokaryotic platforms, due to glycan-mediated evasion of the host immune response. However, protein regions without glycosylated residues capable of inducing neutralizing antibodies could be useful for antigen production in systems that do not carry the glycosylation machinery. To test this hypothesis, the potential antigens NG06 and NG19, located within the non-glycosylated S-RBD region, were selected and expressed in Escherichia coli, purified by FPLC and employed to determine their immunogenic potential through detection of antibodies in serum from immunized rabbits, mice, and COVID-19 patients. IgG antibodies from sera of COVID-19-recovered patients detected the recombinant antigens NG06 and NG19 (A450 nm = 0.80 ± 0.33; 1.13 ± 0.33; and 0.11 ± 0.08 for and negatives controls, respectively). Also, the purified antigens were able to raise polyclonal antibodies in animal models evoking a strong immune response with neutralizing activity in mice model. This research highlights the usefulness of antigens based on the non-N-glycosylated region of RBD from SARS-CoV-2 for candidate vaccine development.

scholarly journals Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 252 ◽  
Author(s):  
Rory Cristiane Fortes De Brito ◽  
Jeronimo Conceição Ruiz ◽  
Jamille Mirelle de Oliveira Cardoso ◽  
Thais Lopes Valentim Di Paschoale Ostolin ◽  
Levi Eduardo Soares Reis ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Visceral Leishmaniasis ◽  
Vaccine Development ◽  
Memory T Cells ◽  
Parasite Burden ◽  
Effector Memory ◽  
Potential Candidate ◽  
Protective Mechanisms ◽  
Strong Immune Response

Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed of Major histocompatibility complex (MHC) class I and II epitopes. For this, we used immunoinformatics features. Following this, we validated these chimeras in a murine model in a thorough memory study and multifunctionality of T cells that contribute to a better elucidation of the immunological protective mechanisms of polyepitope vaccines (chimera A and B) using multicolor flow cytometry. Our results showed that in silico-designed chimeras can elicit polyfunctional T cells producing T helper (Th)1 cytokines, a strong immune response against Leishmania antigen, and the generation of central and effector memory T cells in the spleen cells of vaccinated animals that was able to reduce the parasite burden in this organ. These findings contribute two potential candidate vaccines against VL that can be used in further studies, and help in this complex field of vaccine development against this challenging parasite.

scholarly journals Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1038
Author(s):  
Rahul Chatterjee ◽  
Panchanan Sahoo ◽  
Soumya Ranjan Mahapatra ◽  
Jyotirmayee Dey ◽  
Mrinmoy Ghosh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Population Coverage ◽  
Strong Immune Response ◽  
Chimeric Vaccine

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.

Isolation of post operative hospital acquired infections in a private hospital of Bangladesh and identification of clonal relatedness of E. coli by using Pulse filed gel electrophoresis

2012 ◽  
Vol 6 (2) ◽  
pp. 7-10
Author(s):  
Mohammad Murshed ◽  
Sabeena Shahnaz ◽  
Md. Abdul Malek
Keyword(s):  
Private Hospital ◽  
Isolation And Identification ◽  
College Hospital ◽  
Hospital Acquired Infection ◽  
E Coli ◽  
Hospital Acquired Infections ◽  
Medical College ◽  
Clonal Relatedness ◽  
Hospital Acquired ◽  
Dressing Materials

Isolation and identification of post operative hospital acquired infection was carried out from July 2008 to December 2008 in Holy Family Red Crescent Medical College Hospital (private hospital). The major pathogen of wound infection was E. coli. A total; of 120 samples were collected from the surrounding environment of post operative room like floor, bed sheets, instruments, dressing materials, catheter, nasogastric and endotracheal tube. E. coli (40%) was the predominant organism followed by S. aureus (24%). DNA fingerprinting analysis using pulsed field gel electreopheresis of XbaI restriction digested genomic DNA showed that clonal relatedness between the two clinical nd environmental isolates were 100%.DOI: http://dx.doi.org/10.3329/bjmm.v6i2.19369 Bangladesh J Med Microbiol 2012; 06(02): 7-10

HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

2020 ◽  
Vol 28 ◽  
Author(s):  
Alireza Milani ◽  
Kazem Baesi ◽  
Elnaz Agi ◽  
Ghazal Marouf ◽  
Maryam Ahmadi ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Development ◽  
Treated Group ◽  
Vaccine Antigen ◽  
Accessory Proteins ◽  
Serological Method ◽  
Th2 Immune Response ◽  
Untreated Individuals ◽  
Immunogenic Properties ◽  
Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

scholarly journals Protection and Response of a Tertiary Hospital in Shenzhen, China to the COVID-19 Outbreak—the Practice of the Comprehensive Response Mode

2021 ◽  
pp. 1-17
Author(s):  
Benling Hu ◽  
Le Yang ◽  
Chan Wei ◽  
Min Luo
Keyword(s):  
Prevention And Control ◽  
Tertiary Hospital ◽  
Control Model ◽  
Normal Operation ◽  
Process Reengineering ◽  
Equipment Management ◽  
Hospital Acquired Infection ◽  
Public Health Emergencies ◽  
Hospital Acquired ◽  
And Control

ABSTRACT Objective: To evaluate the management mode for the prevention and control of coronavirus 2019 (COVID-19) transmission utilized at a general hospital in Shenzhen, China, with the aim to maintain the normal operation of the hospital. Methods: From January 2, 2020 to April 23, 2020, Hong Kong–Shenzhen Hospital, a tertiary hospital in Shenzhen, has operated a special response protocol named comprehensive pandemic prevention and control model, which mainly includes six aspects: 1) human resource management; 2) equipment management; 3) logistics management; 4) cleaning, disinfection and process reengineering; 5) environment layout; 6) and training and assessment. The detail of every aspect was described and its efficiency was evaluated. Results: A total of 198,802 patients were received. Of those, 10,821 were hospitalized; 26,767 were received by the emergency department and fever clinics; 288 patients were admitted for observation with fever; and 324 were admitted as suspected cases for isolation. Under the protocol of comprehensive pandemic prevention and control model, no case of hospital-acquired infection with COVID-19 occurred among the inpatients or staff. Conclusion: The present comprehensive response model may be useful in large public health emergencies to ensure appropriate management and protect the health and life of individuals.

The funding and organization of infection control in NHS hospital trusts: a study of infection control professionals' views

2003 ◽  
Vol 16 (2) ◽  
pp. 71-84 ◽  
Author(s):  
B. Croxson ◽  
P. Allen ◽  
J. A. Roberts ◽  
K. Archibald ◽  
S. Crawshaw ◽  
...  
Keyword(s):  
Infection Control ◽  
Nationwide Survey ◽  
Organizational Structures ◽  
Hospital Infection ◽  
Hospital Acquired Infection ◽  
Hospital Infection Control ◽  
Complex Picture ◽  
Ward Level ◽  
Almost All ◽  
Hospital Acquired

The problems associated with hospital-acquired infection have been causing increasing concern in England in recent years. This paper reports the results of a nationwide survey of hospital infection control professionals' views concerning the organizational structures used to manage and obtain funding for control of infection. A complex picture with significant variation between hospitals emerges. Although government policy dictates that specific funding for hospital infection control is formally made available, it is not always the case that infection control professionals have adequate resources to undertake their roles. In some cases this reflects the failure of hospitals' infection control budgetary mechanisms; in others it reflects the effects of decentralizing budgets to directorate or ward level. Some use was made of informal mechanisms either to supplement or to substitute for the formal ones. But almost all infection control professionals still believed they were constrained in their ability to protect the hospital population from the risk of infectious disease. It is clear that recent government announcements that increased effort will be made to support local structures and thereby improve the control of hospital acquired infection are to be welcomed.

scholarly journals The Koala Immune Response to Chlamydial Infection and Vaccine Development—Advancing Our Immunological Understanding

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 380
Author(s):  
Bonnie L Quigley ◽  
Peter Timms
Keyword(s):  
Immune Response ◽  
Chlamydial Infection ◽  
Vaccine Development ◽  
Interleukin 17 ◽  
Phascolarctos Cinereus ◽  
Post Vaccination ◽  
Research Systems ◽  
Cytokine Levels ◽  
Nucleic Acid Assay ◽  
Immunological Research

Chlamydia is a significant pathogen for many species, including the much-loved Australian marsupial, the koala (Phascolarctos cinereus). To combat this situation, focused research has gone into the development and refinement of a chlamydial vaccine for koalas. The foundation of this process has involved characterising the immune response of koalas to both natural chlamydial infection as well as vaccination. From parallels in human and mouse research, it is well-established that an effective anti-chlamydial response will involve a balance of cell-mediated Th1 responses involving interferon-gamma (IFN-γ), humoral Th2 responses involving systemic IgG and mucosal IgA, and inflammatory Th17 responses involving interleukin 17 (IL-17) and neutrophils. Characterisation of koalas with chlamydial disease has shown increased expression within all three of these major immunological pathways and monitoring of koalas’ post-vaccination has detected further enhancements to these key pathways. These findings offer optimism that a chlamydial vaccine for wider distribution to koalas is not far off. Recent advances in marsupial genetic knowledge and general nucleic acid assay technology have moved koala immunological research a step closer to other mammalian research systems. However, koala-specific reagents to directly assay cytokine levels and cell-surface markers are still needed to progress our understanding of koala immunology.

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