scholarly journals Modular vaccine platform based on the norovirus-like particle

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Vili Lampinen ◽  
Suvi Heinimäki ◽  
Olli H. Laitinen ◽  
Marko Pesu ◽  
Minna M. Hankaniemi ◽  
...  
Keyword(s):  
Antibody Production ◽  
High Efficiency ◽  
Vaccine Development ◽  
Protein Antigens ◽  
Vaccine Platform ◽  
Adjuvant Effect ◽  
E Coli ◽  
Virus Like Particle ◽  
Scalable Methods ◽  
Conventional Vaccine

Abstract Background Virus-like particle (VLP) vaccines have recently emerged as a safe and effective alternative to conventional vaccine technologies. The strong immunogenic effects of VLPs can be harnessed for making vaccines against any pathogen by decorating VLPs with antigens from the pathogen. Producing the antigenic pathogen fragments and the VLP platform separately makes vaccine development rapid and convenient. Here we decorated the norovirus-like particle with two conserved influenza antigens and tested for the immunogenicity of the vaccine candidates in BALB/c mice. Results SpyTagged noro-VLP was expressed with high efficiency in insect cells and purified using industrially scalable methods. Like the native noro-VLP, SpyTagged noro-VLP is stable for months when refrigerated in a physiological buffer. The conserved influenza antigens were produced separately as SpyCatcher fusions in E. coli before covalent conjugation on the surface of noro-VLP. The noro-VLP had a high adjuvant effect, inducing high titers of antibody production against the antigens presented on its surface. Conclusions The modular noro-VLP vaccine platform presented here offers a rapid, convenient and safe method to present various soluble protein antigens to the immune system for vaccination and antibody production purposes.

scholarly journals Identification of lipid A deacylase as a novel, highly conserved and protective antigen against enterohemorrhagic Escherichia coli

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maricarmen Rojas-Lopez ◽  
Manuele Martinelli ◽  
Valentina Brandi ◽  
Grégory Jubelin ◽  
Fabio Polticelli ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Vaccine Candidate ◽  
Bacterial Load ◽  
Enterohemorrhagic Escherichia Coli ◽  
Protein Antigens ◽  
E Coli ◽  
Epidemiology Data ◽  
Potential Vaccine

AbstractEnterohemorrhagic E. coli (EHEC) is a major cause of large outbreaks worldwide associated with hemorrhagic colitis and hemolytic uremic syndrome. While vaccine development is warranted, a licensed vaccine, specific for human use, against EHEC is not yet available. In this study, the reverse vaccinology approach combined with genomic, transcriptional and molecular epidemiology data was applied on the EHEC O157:H7 genome to select new potential vaccine candidates. Twenty-four potential protein antigens were identified and one of them (MC001) was successfully expressed onto Generalized Modules for Membrane Antigens (GMMA) delivery system. GMMA expressing this vaccine candidate was immunogenic, raising a specific antibody response. Immunization with the MC001 candidate was able to reduce the bacterial load of EHEC O157:H7 strain in feces, colon and caecum tissues after murine infection. MC001 is homologue to lipid A deacylase enzyme (LpxR), and to our knowledge, this is the first study describing it as a potential vaccine candidate. Gene distribution and sequence variability analysis showed that MC001 is present and conserved in EHEC and in enteropathogenic E. coli (EPEC) strains. Given the high genetic variability among and within E. coli pathotypes, the identification of such conserved antigen suggests that its inclusion in a vaccine might represent a solution against major intestinal pathogenic strains.

scholarly journals A Mycobacteriophage-Based Vaccine Platform: SARS-CoV-2 Antigen Expression and Display

2021 ◽  
Vol 9 (12) ◽  
pp. 2414
Author(s):  
Krista G. Freeman ◽  
Katherine S. Wetzel ◽  
Yu Zhang ◽  
Kira M. Zack ◽  
Deborah Jacobs-Sera ◽  
...  
Keyword(s):  
Single Particle ◽  
High Purity ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Antigen Expression ◽  
Spike Protein ◽  
Infectious Agents ◽  
Protein Antigens ◽  
Vaccine Platform ◽  
Excellent Safety Profile

The explosion of SARS-CoV-2 infections in 2020 prompted a flurry of activity in vaccine development and exploration of various vaccine platforms, some well-established and some new. Phage-based vaccines were described previously, and we explored the possibility of using mycobacteriophages as a platform for displaying antigens of SARS-CoV-2 or other infectious agents. The potential advantages of using mycobacteriophages are that a large and diverse variety of them have been described and genomically characterized, engineering tools are available, and there is the capacity to display up to 700 antigen copies on a single particle approximately 100 nm in size. The phage body may itself be a good adjuvant, and the phages can be propagated easily, cheaply, and to high purity. Furthermore, the recent use of these phages therapeutically, including by intravenous administration, suggests an excellent safety profile, although efficacy can be restricted by neutralizing antibodies. We describe here the potent immunogenicity of mycobacteriophage Bxb1, and Bxb1 recombinants displaying SARS-CoV-2 Spike protein antigens.

scholarly journals A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose

Vaccine ◽  
2012 ◽  
Vol 30 (24) ◽  
pp. 3653-3665 ◽  
Author(s):  
Laura E. Richert ◽  
Amy E. Servid ◽  
Ann L. Harmsen ◽  
Agnieszka Rynda-Apple ◽  
Soo Han ◽  
...  
Keyword(s):  
Single Dose ◽  
Antibody Production ◽  
Vaccine Platform ◽  
Mucosal Antibody ◽  
Virus Like Particle

scholarly journals Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

2021 ◽  
Author(s):  
Mengling Li ◽  
Pengju Guo ◽  
Cen Chen ◽  
Helong Feng ◽  
Wanpo Zhang ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Matrix Protein ◽  
Vaccine Development ◽  
Influenza Pandemic ◽  
Bacteriophage T4 ◽  
Influenza Vaccines ◽  
Next Generation ◽  
Vaccine Platform ◽  
Virus Challenge ◽  
Virus Like Particle

Developing influenza vaccines that protect against a broad range of viruses is a public health priority, and several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is immunogenic, and vaccine platforms that can incorporate multiple antigens with enhanced immunogenicity are desperately needed. In this study, we provided proof-of-concept for the development of next-generation influenza vaccine using T4 phage virus-like particle (VLP) platform. With extracellular domain of influenza matrix protein 2 (M2e) as a readout, we showed that more than 1,280 M2e molecules can be assembled on a 120×90 nanometer phage capsid to form T4-M2e VLPs, which are highly immunogenic and induced complete protection against influenza virus challenge without any addition adjuvant. Potentially, additional conserved antigens or molecular adjuvants could be incorporated into the T4-M2e VLPs to customize influenza vaccines to address different issues. All the components of T4 VLP vaccines can be mass-produced in E. coli in a short time, therefore, providing a rapid approach to deal with the potential influenza pandemic.

scholarly journals CUTANEOUS BASOPHIL HYPERSENSITIVITY

1970 ◽  
Vol 132 (3) ◽  
pp. 546-557 ◽  
Author(s):  
Hal B. Richerson ◽  
Harold F. Dvorak ◽  
Sidney Leskowitz
Keyword(s):  
Skin Reaction ◽  
Skin Test ◽  
Antibody Production ◽  
Delayed Hypersensitivity ◽  
Protein Antigens ◽  
Adjuvant Effect ◽  
Important Contributor ◽  
Test Antigen ◽  
Hypersensitivity Skin

Jones-Mote reactivity, defined as a delayed-type skin reaction, occurs transiently early in the course of immunization with protein antigens or hapten conjugates with or without the adjuvant effect of tubercle bacilli. The skin reaction is typically a flat, well-circumscribed erythema with little induration beginning at about 6 hr, reaching a peak at 18–24 hr, and fading or gone at 48 hr. Immunogenic carrier requirements for hapten-specific Jones-Mote hypersitivity resemble those of antibody production rather than of classic delayed hypersensitivity. Skin test antigen requirements indicate that the Jones-Mote reaction involves an active stimulatory response rather than combination with preformed antibody, since ABA conjugates of nonimmunogenic D-polymers do not work. Studies with ALS and carrageenan suggest that the lymphocyte is an important contributor to the reaction, but the macrophage is not. Because the reactions studied here are operationally different from those described by Jones and Mote and because they have a characteristic histology, the term "cutaneous basophil hypersensitivity" is proposed.

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 An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lucie Jelínková ◽  
Hugo Jhun ◽  
Allison Eaton ◽  
Nikolai Petrovsky ◽  
Fidel Zavala ◽  
...  
Keyword(s):  
Mouse Model ◽  
Malaria Vaccine ◽  
High Titer ◽  
Circumsporozoite Protein ◽  
Infection Model ◽  
Vaccine Platform ◽  
Junctional Region ◽  
Mouse Infection Model ◽  
Virus Like Particle ◽  
Major Surface

AbstractA malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate.

scholarly journals CRIMoClo plasmids for modular assembly and orthogonal chromosomal integration of synthetic circuits in Escherichia coli

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Stefano Vecchione ◽  
Georg Fritz
Keyword(s):  
Escherichia Coli ◽  
Synthetic Biology ◽  
Integrated Circuits ◽  
High Efficiency ◽  
Genetic Circuit ◽  
Dna Assembly ◽  
Chromosomal Integration ◽  
Golden Gate ◽  
Genetic Circuits ◽  
E Coli

Abstract Background Synthetic biology heavily depends on rapid and simple techniques for DNA engineering, such as Ligase Cycling Reaction (LCR), Gibson assembly and Golden Gate assembly, all of which allow for fast, multi-fragment DNA assembly. A major enhancement of Golden Gate assembly is represented by the Modular Cloning (MoClo) system that allows for simple library propagation and combinatorial construction of genetic circuits from reusable parts. Yet, one limitation of the MoClo system is that all circuits are assembled in low- and medium copy plasmids, while a rapid route to chromosomal integration is lacking. To overcome this bottleneck, here we took advantage of the conditional-replication, integration, and modular (CRIM) plasmids, which can be integrated in single copies into the chromosome of Escherichia coli and related bacteria by site-specific recombination at different phage attachment (att) sites. Results By combining the modularity of the MoClo system with the CRIM plasmids features we created a set of 32 novel CRIMoClo plasmids and benchmarked their suitability for synthetic biology applications. Using CRIMoClo plasmids we assembled and integrated a given genetic circuit into four selected phage attachment sites. Analyzing the behavior of these circuits we found essentially identical expression levels, indicating orthogonality of the loci. Using CRIMoClo plasmids and four different reporter systems, we illustrated a framework that allows for a fast and reliable sequential integration at the four selected att sites. Taking advantage of four resistance cassettes the procedure did not require recombination events between each round of integration. Finally, we assembled and genomically integrated synthetic ECF σ factor/anti-σ switches with high efficiency, showing that the growth defects observed for circuits encoded on medium-copy plasmids were alleviated. Conclusions The CRIMoClo system enables the generation of genetic circuits from reusable, MoClo-compatible parts and their integration into 4 orthogonal att sites into the genome of E. coli. Utilizing four different resistance modules the CRIMoClo system allows for easy, fast, and reliable multiple integrations. Moreover, utilizing CRIMoClo plasmids and MoClo reusable parts, we efficiently integrated and alleviated the toxicity of plasmid-borne circuits. Finally, since CRIMoClo framework allows for high flexibility, it is possible to utilize plasmid-borne and chromosomally integrated circuits simultaneously. This increases our ability to permute multiple genetic modules and allows for an easier design of complex synthetic metabolic pathways in E. coli.

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