Molecular Adjuvants for DNA Vaccines: Application, Design, Preparation, and Formulation

Sabbaghi, Ailar; Ghaemi, Amir

doi:10.1007/978-1-0716-0872-2_5

Cited by 15 publications

(12 citation statements)

References 37 publications

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“…However, the kinetics of nucleic acid delivery and expression of the antigen by APCs likely makes adjuvantation very challenging. Enhancement of the immune response to nucleic acid-based vaccines can be achieved by inclusion of plasmids that encode cytokines, costimulatory receptors, or Toll-like receptor (TLR) ligands ( 126 , 127 ).The ability to instruct appropriate (often Th1-mediated) CD4 + T cell responses in newborns and infants is impaired ( 128 , 129 ) and requires adjuvantation with select molecules or combinations that have shown the ability to overcome this impairment ( 27 , 29 , 130 ).…”

Section: Ontogeny Of Vaccine Induced Cd8 + T Cell mentioning

confidence: 99%

Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

Beijnen

Haren

2020

Front. Immunol.

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Infections are most common and most severe at the extremes of age, the young and the elderly. Vaccination can be a key approach to enhance immunogenicity and protection against pathogens in these vulnerable populations, who have a functionally distinct immune system compared to other age groups. More than 50% of the vaccine market is for pediatric use, yet to date vaccine development is often empiric and not tailored to molecular distinctions in innate and adaptive immune activation in early life. With modern vaccine development shifting from whole-cell based vaccines to subunit vaccines also comes the need for formulations that can elicit a CD8+ T cell response when needed, for example, by promoting antigen cross-presentation. While our group and others have identified many cellular and molecular determinants of successful activation of antigen-presenting cells, B cells and CD4+ T cells in early life, much less is known about the ontogeny of CD8+ T cell induction. In this review, we summarize the literature pertaining to the frequency and phenotype of newborn and infant CD8+ T cells, and any evidence of induction of CD8+ T cells by currently licensed pediatric vaccine formulations. In addition, we review the molecular determinants of antigen cross-presentation on MHC I and successful CD8+ T cell induction and discuss potential distinctions that can be made in children. Finally, we discuss recent advances in development of novel adjuvants and provide future directions for basic and translational research in this area.

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Section: Ontogeny Of Vaccine Induced Cd8 + T Cell mentioning

confidence: 99%

Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

Beijnen

Haren

2020

Front. Immunol.

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“…A promising solution to combat poor immunogenicity, for DNA vaccines specifically, are molecular adjuvants. These generally comprise plasmid-encoded signaling molecules such as cytokines, chemokines, and immune costimulatory molecules, but newer approaches include gene knockdown and systems biology (249)(250)(251). For example, Interleukin-2 (IL-2) promote differentiation of naïve T cells into effector cells and facilitates the generation of memory T cells (20).…”

Section: Discussionmentioning

confidence: 99%

Novel Vaccine Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines

et al. 2021

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The success of inactivated and live-attenuated vaccines has enhanced livestock productivity, promoted food security, and attenuated the morbidity and mortality of several human, animal, and zoonotic diseases. However, these traditional vaccine technologies are not without fault. The efficacy of inactivated vaccines can be suboptimal with particular pathogens and safety concerns arise with live-attenuated vaccines. Additionally, the rate of emerging infectious diseases continues to increase and with that the need to quickly deploy new vaccines. Unfortunately, first generation vaccines are not conducive to such urgencies. Within the last three decades, veterinary medicine has spearheaded the advancement in novel vaccine development to circumvent several of the flaws associated with classical vaccines. These third generation vaccines, including DNA, RNA and recombinant viral-vector vaccines, induce both humoral and cellular immune response, are economically manufactured, safe to use, and can be utilized to differentiate infected from vaccinated animals. The present article offers a review of commercially available novel vaccine technologies currently utilized in companion animal, food animal, and wildlife disease control.

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“…Thus, several cytokines (including granulocyte-macrophage colony stimulating factor [GM-CSF], INFs, IL-1, IL-2, IL-6, IL-12, IL-15, IL-18, and chemokines) have huge potential for acting as vaccine adjuvants for the stimulation of potent immune responses against infection, particularly in DNA vaccines. Plasmid DNA vaccines contain a gene encoding the desired antigen with respective epitopes that stimulate adaptive immunity (but with poor immunogenicity) [ 182 ]. However, commercial and traditional vaccine adjuvants cannot enhance the required immunogenicity of DNA vaccines [ 182 ].…”

Section: Immunostimulatory Complexesmentioning

confidence: 99%

“…Plasmid DNA vaccines contain a gene encoding the desired antigen with respective epitopes that stimulate adaptive immunity (but with poor immunogenicity) [ 182 ]. However, commercial and traditional vaccine adjuvants cannot enhance the required immunogenicity of DNA vaccines [ 182 ]. Hence, molecular adjuvants (e.g., cytokines, chemokines, and immune-targeting genes) which are plasmid-encoded proteins, have been assessed as vaccine adjuvants.…”

Section: Immunostimulatory Complexesmentioning

confidence: 99%

Advances in Infectious Disease Vaccine Adjuvants

et al. 2022

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Vaccines are one of the most significant medical interventions in the fight against infectious diseases. Since their discovery by Edward Jenner in 1796, vaccines have reduced the worldwide transmission to eradication levels of infectious diseases, including smallpox, diphtheria, hepatitis, malaria, and influenza. However, the complexity of developing safe and effective vaccines remains a barrier for combating many more infectious diseases. Immune stimulants (or adjuvants) are an indispensable factor in vaccine development, especially for inactivated and subunit-based vaccines due to their decreased immunogenicity compared to whole pathogen vaccines. Adjuvants are widely diverse in structure; however, their overall function in vaccine constructs is the same: to enhance and/or prolong an immunological response. The potential for adverse effects as a result of adjuvant use, though, must be acknowledged and carefully managed. Understanding the specific mechanisms of adjuvant efficacy and safety is a key prerequisite for adjuvant use in vaccination. Therefore, rigorous pre-clinical and clinical research into adjuvant development is essential. Overall, the incorporation of adjuvants allows for greater opportunities in advancing vaccine development and the importance of immune stimulants drives the emergence of novel and more effective adjuvants. This article highlights recent advances in vaccine adjuvant development and provides detailed data from pre-clinical and clinical studies specific to infectious diseases. Future perspectives into vaccine adjuvant development are also highlighted.

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Molecular Adjuvants for DNA Vaccines: Application, Design, Preparation, and Formulation

Cited by 15 publications

References 37 publications

Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation

Novel Vaccine Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines

Advances in Infectious Disease Vaccine Adjuvants

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