Development of mucosal vaccine delivery: an overview on the mucosal vaccines and their adjuvants

Rahmi Anggraeni,Ika Dewi Ana,Hevi Wihadmadyatami 대한백신학회 2022 Clinical and Experimental Vaccine Research Vol.11 No.3

Currently, mucosal infectious diseases are still a very high global health burden, but there are few effective vaccines to prevent mucosal-borne diseases. The development of mucosal vaccines requires the selection of appropriate antigens, delivery system strategies, and adjuvants to increase vaccine efficacy but limited studies have been conducted. The aim of this review is to describe the mucosal immune system, as well as the potential for the development of vaccines and mucosal adjuvants, and their challenges. The study was conducted by applying inclusion criteria for the articles, and a review was conducted by two readers with the agreement. It was known that mucosal vaccination is a potential route to be applied in future preventive efforts through vaccination. However, limited studies have been conducted so far and limited mucosal vaccination has been approved. New technological approaches such as material development involving nano- and micro-patterning are important to intensively open and investigate the potential area of development to provide better vaccination methods.

Mucosal-associated Invariant T cells: A New Player in Innate Immunity

( Yong Wook Park ),( Seung Jung Kee ) 대한류마티스학회 2015 대한류마티스학회지 Vol.22 No.6

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that are restricted by the non-classical major histocompatibility complex class-1b molecule MR1. MAIT cells recognize riboflavin (vitamin B2) derivatives in a MR1-dependent manner. Following antigen recongnition, MAIT cells rapidly produce Th1/Th17 cytokines, such as interferon-γ and interleukin- 17, in an innate-like manner. MAIT cells maintain an activated phenotype throughout the course of an infection, secrete inflammatory cytokines, and have the potential to directly kill infected cells, thus, playing an important role in controlling the host response. In this review, we discuss current knowledge regarding the role of MAIT cells in infectious diseases, cancers, and autoimmune diseases. (J Rheum Dis 2015;22:337-345)

내시경적으로 절제된 신경내분비종양 형태의 직장 신경다발막종

이동건 ( Dong Geon Lee ),이진 ( Jin Lee Bo Mi Kim ),김보미 ( Su Jin Jeong ),정수진 ( Eun Hye Oh ),오은혜 ( Yong Eun Park ),박용은 ( Jongha Park ),박종하 ( Tae Oh Kim ),김태오 대한소화기학회 2021 대한소화기학회지 Vol.77 No.2

Colorectal perineuriomas are benign mucosal-based mesenchymal tumors composed of perineurial cells and show serrated or hyperplastic crypts in epithelium on histopathological evaluation. Most perineuriomas are usually presented as sessile polyps and often as subepithelial tumors. In this case, colonoscopy revealed a rectal subepithelial tumor (measuring approximately 7 mm) with yellowish- colored normal mucosa. A rectal neuroendocrine tumor was suspected, and cap-assisted endoscopic mucosal resection was performed. Histopathological examination of the resected specimen revealed bland spindle cells showing immunopositivity for CD34. The patient was finally diagnosed with rectal perineurioma. (Korean J Gastroenterol 2021;77:84-87)

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Multiple Trauma

Jo, Young-Goun,Choi, Hyun-Jung,Kim, Jung-Chul,Cho, Young-Nan,Kang, Jeong-Hwa,Jin, Hye-Mi,Kee, Seung-Jung,Park, Yong-Wook KOREAN ACADEMY OF MEDICAL SCIENCE 2017 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.32 No.5

<P>Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma.</P>

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Acute Cholecystitis

김정철,진혜미,조영난,권용수,기승정,박용욱 대한의학회 2015 Journal of Korean medical science Vol.30 No.5

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play crucial roles in a variety of diseases, including autoimmunity, infectious diseases, and cancers. However, little is known about the roles of these invariant T cells in acute cholecystitis. The purposes of this study were to examine the levels of MAIT cells and NKT cells in patients with acute cholecystitis and to investigate potential relationships between clinical parameters and these cell levels. Thirty patients with pathologically proven acute cholecystitis and 47 age- and sex-matched healthy controls were enrolled. Disease grades were classified according to the revised Tokyo guidelines (TG13) for the severity assessment for acute cholecystitis. Levels of MAIT and NKT cells in peripheral blood were measured by flow cytometry. Circulating MAIT and NKT cell numbers were significantly lower in acute cholecystitis patients than in healthy controls, and these deficiencies in MAIT cells and NKT cell numbers were associated with aging in acute cholecystitis patients. Notably, a reduction in NKT cell numbers was found to be associated with severe TG13 grade, death, and high blood urea nitrogen levels. The study shows numerical deficiencies of circulating MAIT and NKT cells and age-related decline of these invariant T cells. In addition, NKT cell deficiency was associated with acute cholecystitis severity and outcome. These findings provide an information regarding the monitoring of these changes in circulating MAIT and NKT cell numbers during the course of acute cholecystitis and predicting prognosis.

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Multiple Trauma

조영권,최현정,김정철,조영난,강정화,진혜미,기승정,박용욱 대한의학회 2017 Journal of Korean medical science Vol.32 No.5

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma.

Altered Frequency, Activation, and Clinical Relevance of Circulating Innate and Innate-Like Lymphocytes in Patients With Alcoholic Liver Cirrhosis

Park Ki-Jeong,Jin Hye-Mi,Cho Young-Nan,Yoon Jae Hyun,Kee Seung-Jung,Kim Hyo-Sin,Park Yong-Wook 대한면역학회 2023 Immune Network Vol.23 No.3

Alcoholic liver cirrhosis (ALC) is caused by chronic alcohol overconsumption and might be linked to dysregulated immune responses in the gut-liver axis. However, there is a lack of comprehensive research on levels and functions of innate lymphocytes including mucosal-associated invariant T (MAIT) cells, NKT cells, and NK (NK) cells in ALC patients. Thus, the aim of this study was to examine the levels and function of these cells, evaluate their clinical relevance, and explore their immunologic roles in the pathogenesis of ALC. Peripheral blood samples from ALC patients (n = 31) and healthy controls (HCs, n = 31) were collected. MAIT cells, NKT cells, NK cells, cytokines, CD69, PD-1, and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. Percentages and numbers of circulating MAIT cells, NKT cells, and NK cells were significantly reduced in ALC patients than in HCs. MAIT cell exhibited increased production of IL-17 and expression levels of CD69, PD-1, and LAG-3. NKT cells displayed decreased production of IFN-γ and IL-4. NK cells showed elevated CD69 expression. Absolute MAIT cell levels were positively correlated with lymphocyte count but negatively correlated with C-reactive protein. In addition, NKT cell levels were negatively correlated with hemoglobin levels. Furthermore, log-transformed absolute MAIT cell levels were negatively correlated with the Age, Bilirubin, INR, and Creatinine score. This study demonstrates that circulating MAIT cells, NKT cells, and NK cells are numerically deficient in ALC patients, and the degree of cytokine production and activation status also changed. Besides, some of their deficiencies are related to several clinical parameters. These findings provide important information about immune responses of ALC patients.

TNFα and IL-1β in the synovial fluid facilitate mucosal-associated invariant T (MAIT) cell migration

Kim, Miok,Yoo, Su-Jin,Kang, Seong Wook,Kwon, Jaeyul,Choi, Inpyo,Lee, Chang Hoon Elsevier 2017 Cytokine Vol.99 No.-

<P><B>Abstract</B></P> <P>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affect the joints and inflammatory cell migration into inflamed articular sites contribute to this disease. Among the inflammatory cells, human mucosal-associated invariant T (MAIT) cells were recently recognized as critical cellular component with a pathological role in RA. However, their migratory characteristics are poorly understood. The aim of this study was to determine whether human MAIT cells preferentially traffick to inflamed synovial sites in rheumatoid arthritis patients and to elucidate the underlying mechanism. First, we found that TNFα and IL-1β were elevated in synovial fluid (SF) of RA patients, which resulted in increased expression of E-selectin, ICAM-1 and V-CAM-1 on blood vessel endothelial cells. To understand whether TNFα and IL-1β in the SF facilitated MAIT cell migration, we analyzed CD161<SUP>+</SUP> TCRα7.2<SUP>+</SUP> MAIT and other CD3<SUP>+</SUP> T cells for differences in migratory capacity. Collectively, our results demonstrate that TNFα and IL-1β in the SF facilitated MAIT cell migration dependent on expression of selectin ligand, sialyl Lewis<SUP>X</SUP> (sLe<SUP>X</SUP>) and CCR6 on MAIT cells. We also showed that MAIT cells in the SF from RA patients equipped upregulated sLe<SUP>X</SUP> compared to the peripheral blood of RA patients and healthy persons, which suggest that TNFα and IL-1β mediated expression of E-selectin preferentially attract sLe<SUP>X</SUP> mediated MAIT cell migration into the SF of RA patients.</P>

Mucosal Immune System and M Cell-targeting Strategies for Oral Mucosal Vaccination

Kim, Sae-Hae,Lee, Kyung-Yeol,Jang, Yong-Suk The Korean Association of Immunobiologists 2012 Immune Network Vol.12 No.5

Vaccination is one of the most effective methods available to prevent infectious diseases. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganisms, are one of the first areas where infections are established, and therefore have frontline status in immunity, making mucosa ideal sites for vaccine application. Moreover, vaccination through the mucosal immune system could induce effective systemic immune responses together with mucosal immunity in contrast to parenteral vaccination, which is a poor inducer of effective immunity at mucosal surfaces. Among mucosal vaccines, oral mucosal vaccines have the advantages of ease and low cost of vaccine administration. The oral mucosal immune system, however, is generally recognized as poorly immunogenic due to the frequent induction of tolerance against orally-introduced antigens. Consequently, a prerequisite for successful mucosal vaccination is that the orally introduced antigen should be transported across the mucosal surface into the mucosa-associated lymphoid tissue (MALT). In particular, M cells are responsible for antigen up-take into MALT, and the rapid and effective transcytotic activity of M cells makes them an attractive target for mucosal vaccine delivery, although simple transport of the antigen into M cells does not guarantee the induction of specific immune responses. Consequently, development of mucosal vaccine adjuvants based on an understanding of the biology of M cells has attracted much research interest. Here, we review the characteristics of the oral mucosal immune system and delineate strategies to design effective oral mucosal vaccines with an emphasis on mucosal vaccine adjuvants.

Mucosal Immune System and M Cell-targeting Strategies for Oral Mucosal Vaccination

김새해,장용석,이경열 대한면역학회 2012 Immune Network Vol.12 No.5

Vaccination is one of the most effective methods available to prevent infectious diseases. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganisms,are one of the first areas where infections are established,and therefore have frontline status in immunity, making mucosa ideal sites for vaccine application. Moreover, vaccination through the mucosal immune system could induce effective systemic immune responses together with mucosal immunity in contrast to parenteral vaccination, which is a poor inducer of effective immunity at mucosal surfaces. Among mucosal vaccines, oral mucosal vaccines have the advantages of ease and low cost of vaccine administration. The oral mucosal immune system, however, is generally recognized as poorly immunogenic due to the frequent induction of tolerance against orally-introduced antigens. Consequently,a prerequisite for successful mucosal vaccination is that the orally introduced antigen should be transported across the mucosal surface into the mucosa-associated lymphoid tissue (MALT). In particular, M cells are responsible for antigen uptake into MALT, and the rapid and effective transcytotic activity of M cells makes them an attractive target for mucosal vaccine delivery, although simple transport of the antigen into M cells does not guarantee the induction of specific immune responses. Consequently, development of mucosal vaccine adjuvants based on an understanding of the biology of M cells has attracted much research interest. Here, we review the characteristics of the oral mucosal immune system and delineate strategies to design effective oral mucosal vaccines with an emphasis on mucosal vaccine adjuvants.