scholarly journals Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 504
Author(s):  
Alejandro González-Mora ◽  
Jesús Hernández-Pérez ◽  
Hafiz M. N. Iqbal ◽  
Marco Rito-Palomares ◽  
Jorge Benavides
Keyword(s):  
Phage Display ◽  
Vaccine Development ◽  
Vaccine Delivery ◽  
Effective Vaccine ◽  
Attractive Alternative ◽  
Antigen Delivery ◽  
Phage Display Technology ◽  
Promising Alternative ◽  
Phage Dna ◽  
The Future

Vaccines are considered one of the most important bioproducts in medicine. Since the development of the smallpox vaccine in 1796, several types of vaccines for many diseases have been created. However, some vaccines have shown limitations as high cost and low immune responses. In that regard, bacteriophages have been proposed as an attractive alternative for the development of more cost-effective vaccines. Phage-displayed vaccines consists in the expression of antigens on the phage surface. This approach takes advantage of inherent properties of these particles such as their adjuvant capacity, economic production and high stability, among others. To date, three types of phage-based vaccines have been developed: phage-displayed, phage DNA and hybrid phage-DNA vaccines. Typically, phage display technology has been used for the identification of new and protective epitopes, mimotopes and antigens. In this context, phage particles represent a versatile, effective and promising alternative for the development of more effective vaccine delivery systems which should be highly exploited in the future. This review describes current advances in the development of bacteriophage-based vaccines, with special attention to vaccine delivery strategies. Moreover, the immunological aspects of phage-based vaccines, as well as the applications of phage display for vaccine development, are explored. Finally, important challenges and the future of phage-bases vaccines are discussed.

scholarly journals AN OVERVIEW OF RECOMBINANT VACCINE TECHNOLOGY, ADJUVANTS AND VACCINE DELIVERY METHODS

2016 ◽  
Vol 8 (11) ◽  
pp. 19 ◽  
Author(s):  
Shuaibu Abdullahi Hudu ◽  
Saadatu Haruna Shinkafi ◽  
Shuaibu Umar
Keyword(s):  
Viral Infections ◽  
Vaccine Development ◽  
Journal Article ◽  
Vaccine Delivery ◽  
Recombinant Vaccine ◽  
Effective Vaccine ◽  
Routes Of Administration ◽  
Life Threatening ◽  
New Generation ◽  
And Control

Development of an effective vaccine is of paramount important in disease prevention and control. As such, recombinant technology can serve as a gateway for the development of safe and effective vaccines that can be delivered effectively with an appropriate adjuvant. Therefore, this paper aimed to review the role of recombinant vaccine technology, new adjuvants and the challenge of vaccine delivery. Related peer-reviewed journal article searches were conducted using a subscribed database at the Universiti Putra Malaysia library, involving areas of Health Sciences and Medicine via Medline, SCOPUS and Google Scholar. New generation vaccines include highly purified synthetic or recombinant antigens that stimulate effective cell-mediated immune and mucosal immunity. In order to enhance their efficacy, a number of adjuvants are used. Efforts have also been made to explore the usage of non-invasive routes of administration, devices and equipment for optimized antigen and immune-potentiator delivery of the immune system. Recombinant vaccine technology is rapid, compared to the traditional method of vaccine development and does not require the handling of live viruses. It is, therefore, a promising technology for developing a future vaccine to curb emerging and re-emerging viral infections that may be life-threatening or teratogenic.

scholarly journals Antibiotic-Free Plasmid Stabilization by Operator-Repressor Titration for Vaccine Delivery by Using Live Salmonella enterica Serovar Typhimurium

2005 ◽  
Vol 73 (4) ◽  
pp. 2005-2011 ◽  
Author(s):  
Helen S. Garmory ◽  
Matthew W. Leckenby ◽  
Kate F. Griffin ◽  
Stephen J. Elvin ◽  
Rosa R. Taylor ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Vaccine Development ◽  
Antibiotic Resistance Gene ◽  
Vaccine Delivery ◽  
Marker Genes ◽  
Antigen Delivery ◽  
Protein Vaccine ◽  
Heterologous Antigen ◽  
Serovar Typhimurium

ABSTRACT Live, attenuated bacteria are effective vectors for heterologous antigen delivery. However, loss of heterologous gene-bearing plasmids is problematic, and antibiotics and their resistance genes are not desirable for in vivo DNA vaccine delivery due to biosafety and regulatory concerns. To solve this problem, we engineered the first vaccine delivery strain that has no requirement for antibiotics or other selectable marker genes to maintain the recombinant plasmid. This model strain of Salmonella enterica serovar Typhimurium, SLDAPD, uses operator-repressor titration (ORT) technology, which requires only the short, nonexpressed lacO sequence for selection and maintenance. SLDAPD, recovered from the spleens and Peyer's patches of mice following oral inoculation, was shown to maintain a plasmid that, in contrast, was lost from parental strain SL3261. We also demonstrated successful application of this technology to vaccine development, since SLDAPD carrying a plasmid without an antibiotic resistance gene that expressed the Yersinia pestis F1 antigen was as efficacious in protecting vaccinated mice against plague as the parental SL3261 strain carrying an antibiotic-selected version of this plasmid. Protection of mice against plague by immunization with Salmonella expressing F1 has previously required two or more doses; here we demonstrated for the first time protective immunity after a single oral immunization. This technology can easily be used to convert any suitable attenuated strain to an antibiotic-free ORT strain for recombinant protein vaccine delivery in humans.

scholarly journals Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1034
Author(s):  
Ahmed O. Shalash ◽  
Luke Becker ◽  
Jieru Yang ◽  
Paul Giacomin ◽  
Mark Pearson ◽  
...  
Keyword(s):  
Immune Response ◽  
Worm Burden ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Digestive Enzyme ◽  
Peptide Vaccine ◽  
Effective Vaccine ◽  
Antigen Delivery ◽  
Hookworm Infection ◽  
Linear Arrangement

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL10 or LL10, respectively) groups as self-adjuvanting moieties. BL10 and LL10 induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL10. APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection.

Development and Application of Computational Methods in Phage Display Technology

2020 ◽  
Vol 26 (42) ◽  
pp. 7672-7693 ◽  
Author(s):  
Bifang He ◽  
Anthony Mackitz Dzisoo ◽  
Ratmir Derda ◽  
Jian Huang
Keyword(s):  
Phage Display ◽  
Computational Methods ◽  
Peptide Ligands ◽  
Next Generation ◽  
Phage Display Technology ◽  
Next Generation Sequencing Technology ◽  
Screening Experiments ◽  
Display Technology ◽  
Comprehensive Search ◽  
Generation Sequencing

Background: Phage display is a powerful and versatile technology for the identification of peptide ligands binding to multiple targets, which has been successfully employed in various fields, such as diagnostics and therapeutics, drug-delivery and material science. The integration of next generation sequencing technology with phage display makes this methodology more productive. With the widespread use of this technique and the fast accumulation of phage display data, databases for these data and computational methods have become an indispensable part in this community. This review aims to summarize and discuss recent progress in the development and application of computational methods in the field of phage display. Methods: We undertook a comprehensive search of bioinformatics resources and computational methods for phage display data via Google Scholar and PubMed. The methods and tools were further divided into different categories according to their uses. Results: We described seven special or relevant databases for phage display data, which provided an evidence-based source for phage display researchers to clean their biopanning results. These databases can identify and report possible target-unrelated peptides (TUPs), thereby excluding false-positive data from peptides obtained from phage display screening experiments. More than 20 computational methods for analyzing biopanning data were also reviewed. These methods were classified into computational methods for reporting TUPs, for predicting epitopes and for analyzing next generation phage display data. Conclusion: The current bioinformatics archives, methods and tools reviewed here have benefitted the biopanning community. To develop better or new computational tools, some promising directions are also discussed.

Identification of Small Molecule Binding Sites within Proteins Using Phage Display Technology

2001 ◽  
Vol 4 (7) ◽  
pp. 553-572 ◽  
Author(s):  
D. Rodi ◽  
G. Agoston ◽  
R. Manon ◽  
R. Lapcevich ◽  
S. Green ◽  
...  
Keyword(s):  
Phage Display ◽  
Small Molecule ◽  
Binding Sites ◽  
Phage Display Technology ◽  
Display Technology

scholarly journals The Immune Correlates of Orthohantavirus Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 518
Author(s):  
Joon-Yong Bae ◽  
Jin Il Kim ◽  
Mee Sook Park ◽  
Gee Eun Lee ◽  
Heedo Park ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Zoonotic Transmission ◽  
Effective Vaccine ◽  
Pandemic Preparedness ◽  
Relative Paucity ◽  
Immune Correlates ◽  
Current Vaccine ◽  
Pros And Cons ◽  
Human Infections ◽  
Sense Of Urgency

Zoonotic transmission of orthohantaviruses from rodent reservoirs to humans has been the cause of severe fatalities. Human infections are reported worldwide, but vaccines have been approved only in China and Korea. Orthohantavirus vaccine development has been pursued with no sense of urgency due to the relative paucity of cases in countries outside China and Korea. However, the orthohantaviruses continuously evolve in hosts and thus the current vaccine may not work as well against some variants. Therefore, a more effective vaccine should be prepared against the orthohantaviruses. In this review, we discuss the issues caused by the orthohantavirus vaccine. Given the pros and cons of the orthohantavirus vaccine, we suggest strategies for the development of better vaccines in terms of pandemic preparedness.

scholarly journals Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 140
Author(s):  
Abdellatif Bouazzaoui ◽  
Ahmed A. H. Abdellatif ◽  
Faisal A. Al-Allaf ◽  
Neda M. Bogari ◽  
Saied Al-Dehlawi ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Protein Production ◽  
Vaccine Development ◽  
Effective Vaccine ◽  
The Novel ◽  
Research Teams ◽  
Advantages And Disadvantages ◽  
Rapid Spread ◽  
New Generation ◽  
Conventional Vaccine

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

scholarly journals High-Throughput Sequencing of Phage Display Libraries Reveals Parasitic Enrichment of Indel Mutants Caused by Amplification Bias

2021 ◽  
Vol 22 (11) ◽  
pp. 5513
Author(s):  
Sander Plessers ◽  
Vincent Van Deuren ◽  
Rob Lavigne ◽  
Johan Robben
Keyword(s):  
Amino Acid ◽  
Phage Display ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Target Selection ◽  
Acid Modification ◽  
Phage Display Technology ◽  
Amplification Bias ◽  
Large Deletions ◽  
Depth Analysis

The combination of phage display technology with high-throughput sequencing enables in-depth analysis of library diversity and selection-driven dynamics. We applied short-read sequencing of the mutagenized region on focused display libraries of two homologous nucleic acid modification eraser proteins—AlkB and FTO—biopanned against methylated DNA. This revealed enriched genotypes with small indels and concomitant doubtful amino acid motifs within the FTO library. Nanopore sequencing of the entire display vector showed additional enrichment of large deletions overlooked by region-specific sequencing, and further impacted the interpretation of the obtained amino acid motifs. We could attribute enrichment of these corrupted clones to amplification bias due to arduous FTO display slowing down host cell growth as well as phage production. This amplification bias appeared to be stronger than affinity-based target selection. Recommendations are provided for proper sequence analysis of phage display data, which can improve motive discovery in libraries of proteins that are difficult to display.

scholarly journals The UPTAKE study: implications for the future of COVID-19 vaccination trial recruitment in UK and beyond

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sonika Sethi ◽  
Aditi Kumar ◽  
Anandadeep Mandal ◽  
Mohammed Shaikh ◽  
Claire A. Hall ◽  
...  
Keyword(s):  
Online Survey ◽  
Age Groups ◽  
Small Towns ◽  
Vaccine Uptake ◽  
Effective Vaccine ◽  
Trial Recruitment ◽  
Trial Management ◽  
Cross Sectional ◽  
Study Results ◽  
The Future

Abstract Background Developing a safe and effective vaccine will be the principal way of controlling the COVID-19 pandemic. However, current COVID-19 vaccination trials are not adequately representing a diverse participant population in terms of age, ethnicity and comorbidities. Achieving the representative recruitment targets that are adequately powered to the study remains one of the greatest challenges in clinical trial management. To ensure accuracy and generalisability of the safety and efficacy conclusions generated by clinical trials, it is crucial to recruit patient cohorts as representative as possible of the future target population. Missing these targets can lead to reduced validity of the study results and can often slow down drug development leading to costly delays. Objective This study explores the key factors related to perceptions and participation in vaccination trials. Methods This study involved an anonymous cross-sectional online survey circulated across the UK. Statistical analysis was done in six phases. Multi-nominal logistic models examined demographic and geographic factors that may impact vaccine uptake. Results The survey had 4884 participants of which 9.44% were Black Asian Minority Ethnic (BAME). Overall, 2020 (41.4%) respondents were interested in participating in vaccine trials; 27.6% of the respondents were not interested and 31.1% were unsure. The most interested groups were male (OR = 1.29), graduates (OR = 1.28), the 40–49 and 50–59 age groups (OR = 1.88 and OR = 1.46 respectively) and those with no health issues (OR = 1.06). The least interested groups were BAME (OR = 0.43), those from villages and small towns (OR = 0.66 and 0.54 respectively) and those aged 70 and above (OR = 1.11). Conclusions In order to have a vaccination that is generalisable to the entire population, greater work needs to be done in engaging a diverse cohort of participants. Public health campaigns need to be targeted in improving trial recruitment rates for the elderly, BAME community and the less educated rural population.

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