Abstract Infectious diseases that result from pathogen infection are among the leading causes of human death, with pathogens such as human immunodeficiency virus, malaria, influenza, and ongoing SARS‐COV‐2 viruses constantly threatening the global population. While the mechanisms behind various infectious diseases are not entirely clear and thus retard the development of effective therapeutics, vaccines have served as a universal approach to containing infectious diseases. However, conventional vaccines that solely consist of antigens or simply mix antigens and adjuvants have failed to control various highly infective or deadly pathogens. Biomaterials‐based vaccines have provided a promising solution due to their ability to synergize the function of antigens and adjuvants, troubleshoot delivery issues, home and manipulate immune cells in situ. In this review, we will summarize different types of materials‐based vaccines for generating cellular and humoral responses against pathogens and discuss the design criteria for amplifying the efficacy of materials‐based vaccines against infectious diseases. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
more »
« less
Glycovaccinology: The design and engineering of carbohydrate-based vaccine components
Vaccines remain one of the most important pillars in preventative medicine, providing protection against a wide array of diseases by inducing humoral and/or cellular immunity. Of the many possible candidate antigens for subunit vaccine development, carbohydrates are particularly appealing because of their ubiquitous presence on the surface of all living cells, viruses, and parasites as well as their known interactions with both innate and adaptive immune cells. Indeed, several licensed vaccines leverage bacterial cell-surface carbohydrates as antigens for inducing antigen-specific plasma cells secreting protective antibodies and the development of memory T and B cells. Carbohydrates have also garnered attention in other aspects of vaccine development, for example, as adjuvants that enhance the immune response by either activating innate immune responses or targeting specific immune cells. Additionally, carbohydrates can function as immunomodulators that dampen undesired humoral immune responses to entire protein antigens or specific, conserved regions on antigenic proteins. In this review, we highlight how the interplay between carbohydrates and the adaptive and innate arms of the immune response is guiding the development of glycans as vaccine components that act as antigens, adjuvants, and immunomodulators. We also discuss how advances in the field of synthetic glycobiology are enabling the design, engineering, and production of this new generation of carbohydrate-containing vaccine formulations with the potential to prevent infectious diseases, malignancies, and complex immune disorders.
more »
« less
- Award ID(s):
- 1936823
- PAR ID:
- 10585631
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Biotechnology advances
- ISSN:
- 0734-9750
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Cancer immunotherapies have reshaped the paradigm for cancer treatment over the past decade. Among them, therapeutic cancer vaccines that aim to modulate antigen‐presenting cells and subsequent T cell priming processes are among the first FDA‐approved cancer immunotherapies. However, despite showing benign safety profiles and the capability to generate antigen‐specific humoral and cellular responses, cancer vaccines have been limited by the modest therapeutic efficacy, especially for immunologically cold solid tumors. One key challenge lies in the identification of tumor‐specific antigens, which involves a costly and lengthy process of tumor cell isolation, DNA/RNA extraction, sequencing, mutation analysis, epitope prediction, peptide synthesis, and antigen screening. To address these issues, in situ cancer vaccines have been actively pursued to generate endogenous antigens directly from tumors and utilize the generated tumor antigens to elicit potent cytotoxic T lymphocyte (CTL) response. Biomaterials‐based in situ cancer vaccines, in particular, have achieved significant progress by taking advantage of biomaterials that can synergize antigens and adjuvants, troubleshoot delivery issues, home, and manipulate immune cells in situ. This review will provide an overview of biomaterials‐based in situ cancer vaccines, either living or artificial materials, under development or in the clinic, and discuss the design criteria for in situ cancer vaccines.more » « less
-
Vaccines are a pivotal achievement in public health, offering inexpensive, distributable and highly effective protection against infectious diseases. Despite significant advancements in vaccine development, there are still many diseases for which vaccines are unavailable or offer limited protection. The global impact of the deficiency in vaccine‐induced immunity against these diseases is profound, leading to increased rates of illness, more frequent hospitalizations, and higher mortality rates. Recent studies have demonstrated conjugation mechanisms and delivery methods to co‐present adjuvants and protein epitopes to antigen‐presenting cells, significantly enhancing adaptive immunity. We introduce a novel approach to incorporate an adjuvant into the vaccine by covalently attaching it to whole enveloped virions. Using clickable azide‐enabled viral particles, generated through metabolic incorporation of N‐azidoacetyl glucosamine (GlcNAz), we conjugated the virions with a cyclo‐octyne‐modified CpG‐ODN. Conjugation yielded a potent adjuvant‐virus complex, eliciting higher TLR9‐mediated cell activation of cultured bone marrow‐derived macrophages relative to co‐administered adjuvants and virions. Administration of covalent adjuvant‐virion conjugates increase immune cell stimulation and may provide a generalizable and effective strategy for eliciting a heightened immune response for vaccine development.more » « less
-
Abstract Nucleic acid vaccines are a method of immunization aiming to elicit immune responses akin to live attenuated vaccines. In this method, DNA or messenger RNA (mRNA) sequences are delivered to the body to generate proteins, which mimic disease antigens to stimulate the immune response. Advantages of nucleic acid vaccines include stimulation of both cell‐mediated and humoral immunity, ease of design, rapid adaptability to changing pathogen strains, and customizable multiantigen vaccines. To combat the SARS‐CoV‐2 pandemic, and many other diseases, nucleic acid vaccines appear to be a promising method. However, aid is needed in delivering the fragile DNA/mRNA payload. Many delivery strategies have been developed to elicit effective immune stimulation, yet no nucleic acid vaccine has been FDA‐approved for human use. Nanoparticles (NPs) are one of the top candidates to mediate successful DNA/mRNA vaccine delivery due to their unique properties, including unlimited possibilities for formulations, protective capacity, simultaneous loading, and delivery potential of multiple DNA/mRNA vaccines. This review will summarize the many varieties of novel NP formulations for DNA and mRNA vaccine delivery as well as give the reader a brief synopsis of NP vaccine clinical trials. Finally, the future perspectives and challenges for NP‐mediated nucleic acid vaccines will be explored.more » « less
-
Abstract Adjuvants play a central role in enhancing the immunogenicity of otherwise poorly immunogenic vaccine antigens. Combining adjuvants has the potential to enhance vaccine immunogenicity compared with single adjuvants, although the cellular and molecular mechanisms of combination adjuvants are not well understood. Using the influenza virus hemagglutinin H5 antigen, we define the immunological landscape of combining CpG and MPLA (TLR-9 and TLR-4 agonists, respectively) with a squalene nanoemulsion (AddaVax) using immunologic and transcriptomic profiling. Mice immunized and boosted with recombinant H5 in AddaVax, CpG+MPLA, or AddaVax plus CpG+MPLA (IVAX-1) produced comparable levels of neutralizing antibodies and were equally well protected against the H5N1 challenge. However, after challenge with H5N1 virus, H5/IVAX-1–immunized mice had 100- to 300-fold lower virus lung titers than mice receiving H5 in AddaVax or CpG+MPLA separately. Consistent with enhanced viral clearance, unsupervised expression analysis of draining lymph node cells revealed the combination adjuvant IVAX-1 significantly downregulated immune homeostasis genes, and induced higher numbers of antibody-producing plasmablasts than either AddaVax or CpG+MPLA. IVAX-1 was also more effective after single-dose administration than either AddaVax or CpG+MPLA. These data reveal a novel molecular framework for understanding the mechanisms of combination adjuvants, such as IVAX-1, and highlight their potential for the development of more effective vaccines against respiratory viruses.more » « less
An official website of the United States government

