Phage based vaccines: Methods, formats, and efficacy an overview
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Mohammadreza Rahimian Govar,1,*
1. University of Maragheh
- Introduction: Bacteriophages (simply called phages) are known as viruses that seize bacteria, these virus particles were first identified by Frederick Twort and Felix d'Herelle in 1915 and 1917 respectively. Phages are the most manifold organism on earth. These virus particles can cause infection in their specific bacterium host and do not damage another organism but they can trigger the innate and adaptive immune systems in non–bacteria organisms. Many studies indicate that phages have high potential in genetic engineering especially filamentous ones by the way this high potential convinced scientists to use these viral particles in many biotechnology applications such as vaccine design, cancer therapy, and drug delivery. In this study, we try to examine the methods of phage base vaccine creation and introduce novel studies which use these types of vaccines against infectious diseases and some types of cancer.
- Methods: 1- Article searching was performed by using Phage display, phage-based vaccine, and phage genome engineering as keywords at PubMed and Science direct.
2- Publication date was set on last 5 years at each website
3- The literature involving vaccine designing, phage display, and related studies were selected for further studies
4- Both review and original articles and also editorial book used to gain data for this study
- Results: 1477 and 9843 results were found in PubMed and Science direct respectively after searching related keywords.
The results were reduced to 370 and 2061 after applying the last 5 years' filter.
At last after the criteria check of results 59 items were selected for further studies.
2- phage-based vaccines format
These types of vaccines are set up in two specific systems: phage DNA vaccines and phage display vaccines. Briefly in phage DNA vaccines phage work as a delivery system to hand over a DNA vaccine to the desired cell, in the other hand phage display vaccines known as transgenic viral particles which expressed immunogenic peptides or proteins on their surface. However, the capability of bacteriophage T7 in the combined use of these two formats in a single particle was shown recently. The most abundant type of phages that are used in vaccine design includes T4 phage with Hoc and Soc proteins used for display and also λ bacteriophage with gpD proteins, T7 bacteriophage with gp10B proteins, MS2 bacteriophage with CP proteins, Qβ with A1 proteins M13 with PVIII and PIII proteins.
3- phage-based vaccines that show good function against disease or cancer
λ bacteriophage against BALB/c TUBO mice model.
M2e-Displaying T7 Bacteriophage against Influenza A Virus
T4 Vaccine Platform against influenza
Bacteriophage Qβ against HIV-1
Bacteriophage based vaccine against SARS-Cov 2
Bacteriophage T4 against Anthrax and Plague
Bacteriophage T4 against murine transplantable colon carcinoma
4-methods uses for genetic engineering of phages
Methods for this purpose are divided into two types, genetic methods and chemical methods.
4-1- Genetic methods:
the traditional method cause Homologous Recombination that based on using two different phages to infect a single bacteria cell or homologous recombination between the plasmid and wild-type phage genome
Bacteriophage Recombineering of Electroporated DNA (BRED) this method was firstly described by Marinelli et al and based on using electroporation to enhance the possibility of intaking wild type phage and donor plasmid by bacteria
CRISPR – Cas technology
Reconstruction of phages into the host cell by transforming the assembled DNA in host bacteria
New combined methods e.g CRISPY-BRED and CRISPY-BRIP were applied in recent studies.
4-2- The chemical methods include Amine group modification by NHS, Sulfo-NHS, incorporated NHS with PEG, and Tetrafluorophenyl (TFP) esters. Carboxylate Group modification by the water-soluble 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide hydrochloride (EDC) or water-insoluble dicyclohexylcarbodiimide (DCC) and addition of NHS esters.
Thiol group modification by Maleimides.
Phenol group modification by diazonium compounds.
Using Aldehyde Cross-Linkers e.g Glutaraldehyde.
- Conclusion: Vaccines are the most important weapons of the human race against infection diseases, thus designing the vaccines with high efficacy, safe enough for mass use, and also with fewer side effects can ensure the survival of humanity. Most of the studies indicate that the phage-based vaccine is a reliable tool to fight against cancer and infection disease, in addition, phages are safe because they are unharmed to non-bacterial cells, and they have fewer side effects in comparison with other virus-based vaccines.
- Keywords: Phage display, phage-based vaccine, phage genome engineering
