scholarly journals Arming Filamentous Bacteriophage, a Nature-Made Nanoparticle, for New Vaccine and Immunotherapeutic Strategies

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 437 ◽  
Author(s):  
Rossella Sartorius ◽  
Luciana D’Apice ◽  
Antonella Prisco ◽  
Piergiuseppe De Berardinis
Keyword(s):  
Antigen Expression ◽  
Antigenic Determinants ◽  
Antigen Delivery ◽  
Adaptive Responses ◽  
Bacterial Strains ◽  
Phage Display Technology ◽  
Filamentous Bacteriophage ◽  
Filamentous Bacteriophages ◽  
Delivery Strategies ◽  
Therapeutic Tools

The pharmaceutical use of bacteriophages as safe and inexpensive therapeutic tools is collecting renewed interest. The use of lytic phages to fight antibiotic-resistant bacterial strains is pursued in academic and industrial projects and is the object of several clinical trials. On the other hand, filamentous bacteriophages used for the phage display technology can also have diagnostic and therapeutic applications. Filamentous bacteriophages are nature-made nanoparticles useful for their size, the capability to enter blood vessels, and the capacity of high-density antigen expression. In the last decades, our laboratory focused its efforts in the study of antigen delivery strategies based on the filamentous bacteriophage ‘fd’, able to trigger all arms of the immune response, with particular emphasis on the ability of the MHC class I restricted antigenic determinants displayed on phages to induce strong and protective cytotoxic responses. We showed that fd bacteriophages, engineered to target mouse dendritic cells (DCs), activate innate and adaptive responses without the need of exogenous adjuvants, and more recently, we described the display of immunologically active lipids. In this review, we will provide an overview of the reported applications of the bacteriophage carriers and describe the advantages of exploiting this technology for delivery strategies.

scholarly journals Stimulation of Innate and Adaptive Immunity by Using Filamentous Bacteriophage fd Targeted to DEC-205

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Luciana D’Apice ◽  
Valerio Costa ◽  
Rossella Sartorius ◽  
Maria Trovato ◽  
Marianna Aprile ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Adaptive Immune Response ◽  
Antibody Fragment ◽  
Antigenic Determinants ◽  
Rna Seq ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Filamentous Bacteriophage ◽  
Adaptive Immune

The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC-205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants. By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd. RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response.

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 Chimeric Bovine Respiratory Syncytial Virus with Glycoprotein Gene Substitutions from Human Respiratory Syncytial Virus (HRSV): Effects on Host Range and Evaluation as a Live-Attenuated HRSV Vaccine

2000 ◽  
Vol 74 (3) ◽  
pp. 1187-1199 ◽  
Author(s):  
Ursula J. Buchholz ◽  
Harald Granzow ◽  
Kathrin Schuldt ◽  
Stephen S. Whitehead ◽  
Brian R. Murphy ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Host Range ◽  
Antigen Expression ◽  
Bovine Respiratory Syncytial Virus ◽  
Human Respiratory Syncytial Virus ◽  
Chimeric Virus ◽  
Antigenic Determinants ◽  
Range Restriction ◽  
Successful Recovery ◽  
Syncytial Virus

ABSTRACT We recently developed a system for the generation of infectious bovine respiratory syncytial virus (BRSV) from cDNA. Here, we report the recovery of fully viable chimeric recombinant BRSVs (rBRSVs) that carry human respiratory syncytial virus (HRSV) glycoproteins in place of their BRSV counterparts, thus combining the replication machinery of BRSV with the major antigenic determinants of HRSV. A cDNA encoding the BRSV antigenome was modified so that the complete G and F genes, including the gene start and gene end signals, were replaced by their HRSV A2 counterparts. Alternatively, the BRSV F gene alone was replaced by that of HRSV Long. Each antigenomic cDNA directed the successful recovery of recombinant virus, yielding rBRSV/A2 and rBRSV/LongF, respectively. The HRSV G and F proteins or the HRSV F in combination with BRSV G were expressed efficiently in cells infected with the appropriate chimeric virus and were efficiently incorporated into recombinant virions. Whereas BRSV and HRSV grew more efficiently in bovine and human cells, respectively, the chimeric rBRSV/A2 exhibited intermediate growth characteristics in a human cell line and grew better than either parent in a bovine line. The cytopathology induced by the chimera more closely resembled that of BRSV. BRSV was confirmed to be highly restricted for replication in the respiratory tract of chimpanzees, a host that is highly permissive for HRSV. Interestingly, the rBRSV/A2 chimeric virus was somewhat more competent than BRSV for replication in chimpanzees but remained highly restricted compared to HRSV. This showed that the substitution of the G and F glycoproteins alone was not sufficient to induce efficient replication in chimpanzees. Thus, the F and G proteins contribute to the host range restriction of BRSV but are not the major determinants of this phenotype. Although rBRSV/A2 expresses the major neutralization and protective antigens of HRSV, chimpanzees infected with this chimeric virus were not significantly protected against subsequent challenge with wild-type HRSV. This suggests that the growth restriction of rBRSV/A2 was too great to provide adequate antigen expression and that the capacity of this chimeric vaccine candidate for replication in primates will need to be increased by the importation of additional HRSV genes.

Antigen delivery strategies for mucosal vaccines

1996 ◽  
Vol 26 (8-9) ◽  
pp. 825-834 ◽  
Author(s):  
A.J. Husband ◽  
S. Bao ◽  
S.J. Mcclure ◽  
D.L. Emery ◽  
A.J. Ramsay
Keyword(s):  
Antigen Delivery ◽  
Mucosal Vaccines ◽  
Delivery Strategies

scholarly journals Mechanistic insights into bacterial metabolic reprogramming from omics-integrated genome-scale models

2019 ◽  
Author(s):  
Noushin Hadadi ◽  
Vikash Pandey ◽  
Anush Chiappino-Pepe ◽  
Marian Morales ◽  
Hector Gallart-Ayala ◽  
...  
Keyword(s):  
Metabolic Reprogramming ◽  
Scale Model ◽  
Soil Bioremediation ◽  
Adaptive Responses ◽  
Bacterial Strains ◽  
A Genome ◽  
Successful Establishment ◽  
Xenobiotic Compound ◽  
Genome Scale ◽  
Dynamic Population

ABSTRACTUnderstanding the adaptive responses of individual bacterial strains is crucial for microbiome engineering approaches that introduce new functionalities into complex microbiomes, such as xenobiotic compound metabolism for soil bioremediation. Adaptation requires metabolic reprogramming of the cell, which can be captured by multi-omics, but this data remains formidably challenging to interpret and predict. Here we present a new approach that combines genome-scale metabolic modeling with transcriptomics and exometabolomics, both of which are common tools for studying dynamic population behavior. As a realistic demonstration, we developed a genome-scale model of Pseudomonas veronii 1YdBTEX2, a candidate bioaugmentation agent for accelerated metabolism of mono-aromatic compounds in soil microbiomes, while simultaneously collecting experimental data of P. veronii metabolism during growth phase transitions. Predictions of the P. veronii growth rates and specific metabolic processes from the integrated model closely matched experimental observations. We conclude that integrative and network-based analysis can help build predictive models that accurately capture bacterial adaptation responses. Further development and testing of such models may considerably improve the successful establishment of bacterial inoculants in more complex systems.

Role of Infectious Virus Expression and Immune Response in Retrovirus-Induced Oncogenesis

1984 ◽  
Vol 70 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Paola Zanovello ◽  
Emma D'Andrea ◽  
Franca Ronchese ◽  
Anita De Rossi ◽  
Dino Collavo ◽  
...  
Keyword(s):  
Immune Response ◽  
Cytotoxic T Lymphocyte ◽  
Leukemia Virus ◽  
Plaque Assay ◽  
Low Frequency ◽  
Antigen Expression ◽  
Antigenic Determinants ◽  
Newborn Mice ◽  
Surface Antigen Expression ◽  
Virus Expression

Some of the parameters involved in retrovirus-induced oncogenesis were analyzed in newborn mice injected with Moloney-murine leukemia virus (M-MuLV) as well as in adults who received the virus by the intraperitoneal (i.p.) or intrathymic (i.t.) route. The neonatally injected mice were permissive for both viral replication and virus-induced cell-surface antigen expression on thymus cells, peripheral T and B lymphocytes, and macrophages, whereas the M-MuLV was not present in the adult i.p. injected mice. Instead, in i.t. injected mice, the virus was expressed in thymus and peripheral T cells only, but was not detected in tail extracts as assessed by means of the UV-XC plaque assay. Lack of virus spread in adult-treated animals correlated with a prompt humoral and cellular immune response, whereas the highly viremic newborn inoculated mice showed negligible virus-specific antibody production and an extremely low frequency of splenic cytotoxic T lymphocyte precursors. Moreover, immune response in both groups of adult-treated mice efficiently prevented tumor induction by Moloney-murine sarcoma virus (M-MuSV), which has the same antigenic determinants as M-MuLV, its natural helper. In contrast, M-MuSV sarcomas grew progressively in newborn inoculated mice and killed the host. Finally, 80 % of neonatally injected mice developed lymphomas, whereas all treated adults remained free of disease for more than 15 months. These findings imply that the immune response may, in fact, prevent retrovirus-induced oncogenesis through restriction of virus replication and/or destruction of virus-infected cells.

scholarly journals Autodisplay: Development of an Efficacious System for Surface Display of Antigenic Determinants in Salmonella Vaccine Strains

2003 ◽  
Vol 71 (4) ◽  
pp. 1944-1952 ◽  
Author(s):  
Uwe Kramer ◽  
Konstantin Rizos ◽  
Heiko Apfel ◽  
Ingo B. Autenrieth ◽  
Claus T. Lattemann
Keyword(s):  
Fusion Protein ◽  
Vaccine Strain ◽  
Surface Display ◽  
T Cell Response ◽  
Modular System ◽  
Antigenic Determinants ◽  
Antigen Delivery ◽  
Bacterial Surface ◽  
Serovar Typhimurium

ABSTRACT To optimize antigen delivery by Salmonella vaccine strains, a system for surface display of antigenic determinants was established by using the autotransporter secretion pathway of gram-negative bacteria. A modular system for surface display allowed effective targeting of heterologous antigens or fragments thereof to the bacterial surface by the autotransporter domain of AIDA-I, the Escherichia coli adhesin involved in diffuse adherence. A major histocompatibility complex class II-restricted epitope, comprising amino acids 74 to 86 of the Yersinia enterocolitica heat shock protein Hsp60 (Hsp6074-86), was fused to the AIDA-I autotransporter domain, and the resulting fusion protein was expressed at high levels on the cell surface of E. coli and Salmonella enterica serovar Typhimurium. Colonization studies in mice vaccinated with Salmonella strains expressing AIDA-I fusion proteins demonstrated high genetic stability of the generated vaccine strain in vivo. Furthermore, a pronounced T-cell response against Yersinia Hsp6074-86 was induced in mice vaccinated with a Salmonella vaccine strain expressing the Hsp6074-86-AIDA-I fusion protein. This was shown by monitoring Yersinia Hsp60-stimulated IFN-γ secretion and proliferation of splenic T cells isolated from vaccinated mice. These results demonstrate that the surface display of antigenic determinants by the autotransporter pathway deserves special attention regarding the application in live attenuated Salmonella vaccine strains.

scholarly journals The PhoQ-Activating Potential of Antimicrobial Peptides Contributes to Antimicrobial Efficacy and Is Predictive of the Induction of Bacterial Resistance

2007 ◽  
Vol 51 (12) ◽  
pp. 4374-4381 ◽  
Author(s):  
Jason Kindrachuk ◽  
Nicole Paur ◽  
Carla Reiman ◽  
Erin Scruten ◽  
Scott Napper
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Immune Defense ◽  
Minimal Bactericidal Concentration ◽  
Adaptive Responses ◽  
Bacterial Strains ◽  
Concentration Data ◽  
Antimicrobial Efficiency ◽  
Novel Strategy ◽  
Therapeutic Administration

ABSTRACT Antimicrobial peptides (AMPs) are among the leading candidates to replace antibiotics which have been rendered ineffective by the evolution of resistant bacterial strains. Concerns do exist, however, that the therapeutic administration of AMPs may also select for resistant strains but with much more dire consequences, as these peptides represent an endogenous and essential component of host immune defense. The recent demonstration that AMPs function as ligands for the bacterial sensory kinase PhoQ for the initiation of virulence and adaptive responses lends credence to these concerns. While the ability to serve as PhoQ ligands suggests that the therapeutic administration of AMPs could (i) exacerbate infections by promoting bacterial virulence and (ii) select resistant mutants by encouraging adaptive behaviors, it also provides a rational basis for AMP selection and optimization. Here, we demonstrate that derivatives of a representative AMP have differential abilities to serve as PhoQ ligands and that this correlates with the ability to induce bacterial adaptive responses. We propose that PhoQ-activating potential is a logical parameter for AMP optimization and introduce a novel strategy for the treatment of minimal bactericidal concentration data that permits the discrimination and quantification of the contributions of PhoQ-activating potential and direct antimicrobial activity to net antimicrobial efficiency.

scholarly journals CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rebecca Conners ◽  
Mathew McLaren ◽  
Urszula Łapińska ◽  
Kelly Sanders ◽  
M. Rhia L. Stone ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Gram Negative Bacteria ◽  
Filamentous Bacteriophage ◽  
Cryo Electron Microscopy ◽  
Channel Opening ◽  
Filamentous Bacteriophages ◽  
Gated Channel ◽  
Model Channel ◽  
Bacterial Outer Membrane ◽  
Similarities And Differences

AbstractThe Ff family of filamentous bacteriophages infect gram-negative bacteria, but do not cause lysis of their host cell. Instead, new virions are extruded via the phage-encoded pIV protein, which has homology with bacterial secretins. Here, we determine the structure of pIV from the f1 filamentous bacteriophage at 2.7 Å resolution by cryo-electron microscopy, the first near-atomic structure of a phage secretin. Fifteen f1 pIV subunits assemble to form a gated channel in the bacterial outer membrane, with associated soluble domains projecting into the periplasm. We model channel opening and propose a mechanism for phage egress. By single-cell microfluidics experiments, we demonstrate the potential for secretins such as pIV to be used as adjuvants to increase the uptake and efficacy of antibiotics in bacteria. Finally, we compare the f1 pIV structure to its homologues to reveal similarities and differences between phage and bacterial secretins.

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