Recent advances on HIV DNA vaccines development: Stepwise improvements to clinical trials

Rezaei, Tayebeh; Khalili, Saeed; Baradaran, Behzad; Mosafer, Jafar; Rezaei, Sarah; Mokhtarzadeh, Ahad; Guárdia, Miguel de la

doi:10.1016/j.jconrel.2019.10.045

Cited by 24 publications

(30 citation statements)

References 148 publications

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“…In comparison, there was less cellular uptake of 4N+{FAM} ON and it was only present in the cytoplasm. These results indicate that ONs with phosphate modifications such as N+ or Ts might be suitable tools for the application of DNA and RNA vaccines [ 60 ], for the treatment of cancer [ 61 ], infectious diseases [ 62 ], and neurological disorders [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

Bayarjargal

Hale

et al. 2021

Beilstein J. Org. Chem.

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Two phosphate modifications were introduced into the DNA backbone using the Staudinger reaction between the 3’,5’-dinucleoside β-cyanoethyl phosphite triester formed during DNA synthesis and sulfonyl azides, 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide (N+ azide) or p-toluenesulfonyl (tosyl or Ts) azide, to provide either a zwitterionic phosphoramidate with N+ modification or a negatively charged phosphoramidate for Ts modification in the DNA sequence. The incorporation of these N+ and Ts modifications led to the formation of thermally stable parallel DNA triplexes, regardless of the number of modifications incorporated into the oligodeoxynucleotides (ONs). For both N+ and Ts-modified ONs, the antiparallel duplexes formed with complementary RNA were more stable than those formed with complementary DNA (except for ONs with modification in the middle of the sequence). Additionally, the incorporation of N+ modifications led to the formation of duplexes with a thermal stability that was less dependent on the ionic strength than native DNA duplexes. The thermodynamic analysis of the melting curves revealed that it is the reduction in unfavourable entropy, despite the decrease in favourable enthalpy, which is responsible for the stabilisation of duplexes with N+ modification. N+ONs also demonstrated greater resistance to nuclease digestion by snake venom phosphodiesterase I than the corresponding Ts-ONs. Cell uptake studies showed that Ts-ONs can enter the nucleus of mouse fibroblast NIH3T3 cells without any transfection reagent, whereas, N+ONs remain concentrated in vesicles within the cytoplasm. These results indicate that both N+ and Ts-modified ONs are promising for various in vivo applications.

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Section: Discussionmentioning

confidence: 99%

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

Bayarjargal

Hale

et al. 2021

Beilstein J. Org. Chem.

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“…DNA vaccine technology has been intensively used to develop vaccines against various pathogens ( 54 , 55 ), cancer ( 56 ), and autoimmune disorders ( 57 ). For example, the human immunodeficiency virus-1 (both as a prophylactic and an immunotherapeutic vaccine) ( 58 , 59 ), Zika virus ( 60 ), and Ebola virus vaccines ( 61 ) are currently in clinical trials. Comparatively, little progress has been made toward developing DNA vaccines against parasitic diseases, although several pre-clinical studies have shown promising results against hookworm infections ( 62 , 63 ), malaria ( 64 , 65 ), leishmaniasis ( 66 , 67 ), and schistosomiasis ( 68 , 69 ).…”

Section: Prospects and Challenges For Anti-sths Vaccine Designmentioning

confidence: 99%

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

Zawawi

Else

2020

Front. Immunol.

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Parasitic helminths infect over one-fourth of the human population resulting in significant morbidity, and in some cases, death in endemic countries. Despite mass drug administration (MDA) to school-aged children and other control measures, helminth infections are spreading into new areas. Thus, there is a strong rationale for developing anthelminthic vaccines as cost-effective, long-term immunological control strategies, which, unlike MDA, are not haunted by the threat of emerging drug-resistant helminths nor limited by reinfection risk. Advances in vaccinology, immunology, and immunomics include the development of new tools that improve the safety, immunogenicity, and efficacy of vaccines; and some of these tools have been used in the development of helminth vaccines. The development of anthelminthic vaccines is fraught with difficulty. Multiple lifecycle stages exist each presenting stage-specific antigens. Further, helminth parasites are notorious for their ability to dampen down and regulate host immunity. One of the first significant challenges in developing any vaccine is identifying suitable candidate protective antigens. This review explores our current knowledge in lead antigen identification and reports on recent pre-clinical and clinical trials in the context of the soil-transmitted helminths Trichuris , the hookworms and Ascaris . Ultimately, a multivalent anthelminthic vaccine could become an essential tool for achieving the medium-to long-term goal of controlling, or even eliminating helminth infections.

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“…Nucleic acid-based vaccines combine the positive attributes of both subunit vaccines and live-attenuated vaccines, and there has been substantial research into this type of vaccine for diverse diseases, over the last three decades [ 118 ]. These vaccines involve direct immunization through the delivery of DNA or RNA sequences encoding the antigen, and have as their main advantages, their purity and the simplicity by which this type of vaccine can be produced [ 119 , 120 ]. In addition, nucleic acid-based vaccines can be manufactured rapidly on a large scale and are relatively low-cost [ 95 , 121 ].…”

Section: Sars-cov-2 Vaccine Platformsmentioning

confidence: 99%

Novel insights into the treatment of SARS-CoV-2 infection: An overview of current clinical trials

Oroojalian

Haghbin

Baradaran

et al. 2020

International Journal of Biological Macromolecules

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The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetration into cells, a set of drugs, such as chloroquine, hydroxychloroquine, camostat mesylate have been tested in clinical trials to suppress this event. In addition to angiotensin-converting enzyme 2, the role of CD147 in the viral entrance has also been proposed. Mepolizumab has shown to be effective in blocking the virus's cellular entrance. Antiviral drugs, such as remdesivir, ritonavir, oseltamivir, darunavir, lopinavir, zanamivir, peramivir, and oseltamivir, have also been tested as treatments for COVID-19. Regarding preventive vaccines, the whole virus, vectors, nucleic acids, and structural subunits have been suggested for vaccine development. Mesenchymal stem cells and natural killer cells could also be used against SARS-CoV-2. All the above-mentioned strategies, as well as the role of nanomedicine for the diagnosis and treatment of SARS-CoV-2 infection, have been discussed in this review.

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Recent advances on HIV DNA vaccines development: Stepwise improvements to clinical trials

Cited by 24 publications

References 148 publications

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

Novel insights into the treatment of SARS-CoV-2 infection: An overview of current clinical trials

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