TY  - CONF
AU  - Panić, Marko
AU  - Prijić, Ivana
AU  - Simić, Mihajlo
AU  - Ćuruvija, Ivana
AU  - Lukić, Ivana
AU  - Drgačević, Luka
AU  - Kojić, Milan
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/880
AB  - Diphtheria and tetanus, once formidable causes of morbidity and mortality worldwide, have seen their threats markedly diminished through the advent and widespread use of vaccines. This review article delves into the historical journey of diphtheria and tetanus vaccines, evaluates their current status in global immunization programs, and explores future perspectives in their evolution and implementation. The inception of diphtheria and tetanus vaccines marked a pivotal shift in infectious disease control. The development of diphtheria toxoid by Emil von Behring in the late 19th century and the subsequent creation of tetanus toxoid in the early 20th century set the stage for large-scale immunization efforts. These efforts were bolstered in the mid-20th century with the integration of these toxoids into combination vaccines, notably the DTP (diphtheria-tetanus-pertussis) vaccine, facilitating broader immunization coverage and enhanced public health outcomes. Currently, the inclusion of diphtheria and tetanus vaccines in national immunization schedules has led to a significant decline in the incidence of these diseases globally. However, challenges remain, including disparities in vaccine coverage and the emergence of non-toxigenic strains causing diphtheria. The review highlights the WHO’s strategies towards achieving higher immunization coverage and the importance of maintaining high vaccination rates to prevent resurgence. Looking forward, the review discusses the ongoing research and development aimed at improving vaccine formulations, reducing adverse reactions, and enhancing the efficacy and durability of protection. Innovations such as nanoparticle vaccines and DNA vaccines are explored as potential avenues for future advancements. Additionally, the review addresses the critical role of global health governance in addressing vaccine hesitancy, improving access in low-resource settings, and coordinating responses to outbreaks. In conclusion, while the battle against diphtheria and tetanus has seen significant victories, continuous efforts in vaccine innovation, policy implementation, and global cooperation are essential to sustain these gains and achieve the ultimate goal of global eradication.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
T1  - Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions
EP  - 169
SP  - 169
UR  - https://hdl.handle.net/21.15107/rcub_intor_880
ER  - 

@conference{
author = "Panić, Marko and Prijić, Ivana and Simić, Mihajlo and Ćuruvija, Ivana and Lukić, Ivana and Drgačević, Luka and Kojić, Milan",
year = "2024",
abstract = "Diphtheria and tetanus, once formidable causes of morbidity and mortality worldwide, have seen their threats markedly diminished through the advent and widespread use of vaccines. This review article delves into the historical journey of diphtheria and tetanus vaccines, evaluates their current status in global immunization programs, and explores future perspectives in their evolution and implementation. The inception of diphtheria and tetanus vaccines marked a pivotal shift in infectious disease control. The development of diphtheria toxoid by Emil von Behring in the late 19th century and the subsequent creation of tetanus toxoid in the early 20th century set the stage for large-scale immunization efforts. These efforts were bolstered in the mid-20th century with the integration of these toxoids into combination vaccines, notably the DTP (diphtheria-tetanus-pertussis) vaccine, facilitating broader immunization coverage and enhanced public health outcomes. Currently, the inclusion of diphtheria and tetanus vaccines in national immunization schedules has led to a significant decline in the incidence of these diseases globally. However, challenges remain, including disparities in vaccine coverage and the emergence of non-toxigenic strains causing diphtheria. The review highlights the WHO’s strategies towards achieving higher immunization coverage and the importance of maintaining high vaccination rates to prevent resurgence. Looking forward, the review discusses the ongoing research and development aimed at improving vaccine formulations, reducing adverse reactions, and enhancing the efficacy and durability of protection. Innovations such as nanoparticle vaccines and DNA vaccines are explored as potential avenues for future advancements. Additionally, the review addresses the critical role of global health governance in addressing vaccine hesitancy, improving access in low-resource settings, and coordinating responses to outbreaks. In conclusion, while the battle against diphtheria and tetanus has seen significant victories, continuous efforts in vaccine innovation, policy implementation, and global cooperation are essential to sustain these gains and achieve the ultimate goal of global eradication.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april",
title = "Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions",
pages = "169-169",
url = "https://hdl.handle.net/21.15107/rcub_intor_880"
}

Panić, M., Prijić, I., Simić, M., Ćuruvija, I., Lukić, I., Drgačević, L.,& Kojić, M.. (2024). Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
Serbian Society for Microbiology., 169-169.
https://hdl.handle.net/21.15107/rcub_intor_880

Panić M, Prijić I, Simić M, Ćuruvija I, Lukić I, Drgačević L, Kojić M. Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april. 2024;:169-169.
https://hdl.handle.net/21.15107/rcub_intor_880 .

Panić, Marko, Prijić, Ivana, Simić, Mihajlo, Ćuruvija, Ivana, Lukić, Ivana, Drgačević, Luka, Kojić, Milan, "Diphtheria and tetanus vaccines: a historical overview, present achievements, and future directions" in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april (2024):169-169,
https://hdl.handle.net/21.15107/rcub_intor_880 .

TY  - CONF
AU  - Prijić, Ivana
AU  - Panić, Marko
AU  - Simić, Mihajlo
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Lukić, Ivana
AU  - Dragačević, Luka
AU  - Kojić, Milan
PY  - 2024
UR  - http://intor.torlakinstitut.com/handle/123456789/877
AB  - Diphtheria toxin is a single polypeptide chain produced by toxigenic strains of Corynebacterium diphtheriae that causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis. Formaldehyde (chemical) detoxification converts diphtheria toxin into toxoid, which is used in diphtheria vaccine production. Recombinant, genetically detoxified diphtheria toxin is superior in terms of safety and purity, but it has still not found its application in recombinant diphtheria vaccine production. Both chemically and genetically inactivated forms of the diphtheria toxin have proven effective as protein carriers in conjugate vaccines. The goal of this study was to create a plasmid construct which can be used to express a genetically inactivated diphtheria toxin. Gene coding for diphtheria toxin was cloned into pMALHisEk expression vector and introduced into DH5α competent Escherichia coli cells. Three site-directed point mutations, which led to three amino acid substitutions (G52E-substitutes glycine with glutamic acid, G79D- substitutes glycine with aspartic acid, E148D- substitutes glutamic acid with aspartic acid) were conducted. A single G52E amino acid substitution is responsible for the loss of the enzymatic activity of the diphtheria toxin. G79D is recognized as a good candidate site for combining with other mutations in vaccine development and E148D may be a good candidate as carrier protein because it could reduce both the stability of NAD binding and catalytic activity of the enzyme. Each individual mutation is sufficient for toxin inactivation, but together they ensure non-toxicity, preventing reversion to the wild-type sequence. All mutations were confirmed by DNA sequencing. Recombinant diphtheria toxoid could serve as a potential vaccine epitope or protein carrier for conjugate vaccines. Further optimization of recombinant protein expression in Escherichia coli should provide sufficient quantities of soluble recombinant protein for further testing of its safety, immunogenicity and protection.
PB  - Serbian Society for Microbiology
C3  - XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
T1  - Inactivation of diphtheria toxin by site-directed mutagenesis
EP  - 115
SP  - 115
UR  - https://hdl.handle.net/21.15107/rcub_intor_877
ER  - 

@conference{
author = "Prijić, Ivana and Panić, Marko and Simić, Mihajlo and Blagojević, Veljko and Ćuruvija, Ivana and Lukić, Ivana and Dragačević, Luka and Kojić, Milan",
year = "2024",
abstract = "Diphtheria toxin is a single polypeptide chain produced by toxigenic strains of Corynebacterium diphtheriae that causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis. Formaldehyde (chemical) detoxification converts diphtheria toxin into toxoid, which is used in diphtheria vaccine production. Recombinant, genetically detoxified diphtheria toxin is superior in terms of safety and purity, but it has still not found its application in recombinant diphtheria vaccine production. Both chemically and genetically inactivated forms of the diphtheria toxin have proven effective as protein carriers in conjugate vaccines. The goal of this study was to create a plasmid construct which can be used to express a genetically inactivated diphtheria toxin. Gene coding for diphtheria toxin was cloned into pMALHisEk expression vector and introduced into DH5α competent Escherichia coli cells. Three site-directed point mutations, which led to three amino acid substitutions (G52E-substitutes glycine with glutamic acid, G79D- substitutes glycine with aspartic acid, E148D- substitutes glutamic acid with aspartic acid) were conducted. A single G52E amino acid substitution is responsible for the loss of the enzymatic activity of the diphtheria toxin. G79D is recognized as a good candidate site for combining with other mutations in vaccine development and E148D may be a good candidate as carrier protein because it could reduce both the stability of NAD binding and catalytic activity of the enzyme. Each individual mutation is sufficient for toxin inactivation, but together they ensure non-toxicity, preventing reversion to the wild-type sequence. All mutations were confirmed by DNA sequencing. Recombinant diphtheria toxoid could serve as a potential vaccine epitope or protein carrier for conjugate vaccines. Further optimization of recombinant protein expression in Escherichia coli should provide sufficient quantities of soluble recombinant protein for further testing of its safety, immunogenicity and protection.",
publisher = "Serbian Society for Microbiology",
journal = "XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april",
title = "Inactivation of diphtheria toxin by site-directed mutagenesis",
pages = "115-115",
url = "https://hdl.handle.net/21.15107/rcub_intor_877"
}

Prijić, I., Panić, M., Simić, M., Blagojević, V., Ćuruvija, I., Lukić, I., Dragačević, L.,& Kojić, M.. (2024). Inactivation of diphtheria toxin by site-directed mutagenesis. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april
Serbian Society for Microbiology., 115-115.
https://hdl.handle.net/21.15107/rcub_intor_877

Prijić I, Panić M, Simić M, Blagojević V, Ćuruvija I, Lukić I, Dragačević L, Kojić M. Inactivation of diphtheria toxin by site-directed mutagenesis. in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april. 2024;:115-115.
https://hdl.handle.net/21.15107/rcub_intor_877 .

Prijić, Ivana, Panić, Marko, Simić, Mihajlo, Blagojević, Veljko, Ćuruvija, Ivana, Lukić, Ivana, Dragačević, Luka, Kojić, Milan, "Inactivation of diphtheria toxin by site-directed mutagenesis" in XIII Congress of microbiologists of Serbia with international participation, Mikromed regio 5, From biotechnology to human and planetary health, 4-6 april (2024):115-115,
https://hdl.handle.net/21.15107/rcub_intor_877 .