Methods of Studying Human Dendritic Cells Applicable to Assessing Vaccine Efficacy

Author(s):  
VYu Talayev ◽  
MV Svetlova ◽  
IY Zaichenko ◽  
ON Babaykina ◽  
EV Voronina

Introduction: Vaccines are one of the most effective means of preventing infectious diseases. Their effectiveness and safety are guaranteed by studies of vaccine properties, during their development and during the mandatory preclinical and clinical trials of each new vaccine. Additional information on the mechanisms of vaccine action on human immune system cells can be obtained using in vitro immune response models. The objective of the study was to determine applicability of certain methods of studying human dendritic cells in vitro to assessing the effect of vaccines. Dendritic cells are the most active antigen presenting cells, which play a key role in triggering a primary immune response to an infection or vaccine. Materials and methods: We studied the effect of vaccines on the maturation of dendritic cells, their phagocytic activity and the ability to stimulate T-lymphocytes in vitro. Results: To test the methods, we used vaccines with a known pattern of action on the immune system. All the vaccines induced the expression of dendritic cell maturation markers. At the same time, different vaccines induced a different set of markers and the degree of expression of these molecules. Quantitative methods for assessing phagocytosis and stimulating activity of dendritic cells are described. Conclusion: Methods for evaluation of phagocytosis, phenotypic maturation and functional properties of dendritic cells have been shown to be useful for evaluation of vaccine action. In our opinion, these methods, as a complement to traditional methods for evaluating the immune response, can be used to investigate the action of prototype vaccines at the stage of their development and preclinical trials.

Author(s):  
V.Yu. Talaev ◽  
O.N. Babaikina ◽  
M.V. Talaeva ◽  
E.V. Voronina ◽  
I.E. Zaichenko

The most important means of measles control is live measles vaccine, the high epidemiological effectiveness of which is confirmed by half a century of its use. There is a question of the need to further improve the effectiveness of vaccine prophylaxis, in particular, by increasing the immunogenicity of the used vaccine given the increase in the morbidity of measles in recent years. Investigation of effect features of existing vaccine variants is necessary to identify possible ways to increase their immunogenicity. We investigated the effect of measles culture live vaccine on the maturation of human dendritic cells – the most specialized antigen-presenting cells involved in the induction of an immune response. In vitro incubation of monocytic derived immature dendritic cells with the vaccine initiates the process of their partial maturation, which is manifested in an increase in the number of cells carrying molecules CD86, CD83 and ICOSL (CD275).At the same time they have a reduced expression level of the HLA-DR molecule and chemokine receptors CCR7 and CXCR5 involved in the migration of dendritic cells to peripheral lymphoid organs. In our opinion, the relative weak side of measles vaccine effect on dendritic cell maturation is a factor limiting the immunogenicity of the vaccine, which must be taken into account when developing new measles vaccines.


2021 ◽  
Vol 22 (15) ◽  
pp. 8044
Author(s):  
Mohammed Yusuf Zanna ◽  
Abd Rahaman Yasmin ◽  
Abdul Rahman Omar ◽  
Siti Suri Arshad ◽  
Abdul Razak Mariatulqabtiah ◽  
...  

Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout the body. They are the most efficient, potent, and professional antigen-presenting cells (APCs) of the immune system, inducing and dispersing a primary immune response by the activation of naïve T-cells, and playing an important role in the induction and maintenance of immune tolerance under homeostatic conditions. Thus, this review has elucidated the general aspects of DCs as well as the current dynamic perspectives and distribution of DCs in humans and in various species of animals that includes mouse, rat, birds, dog, cat, horse, cattle, sheep, pig, and non-human primates. Besides the role that DCs play in immune response, they also play a pathogenic role in many diseases, thus becoming a target in disease prevention and treatment. In addition, its roles in clinical immunology have also been addressed, which include its involvement in transplantation, autoimmune disease, viral infections, cancer, and as a vaccine target. Therefore, based on the current knowledge and understanding of the important roles they play, DCs can be used in the future as a powerful tool for manipulating the immune system.


2019 ◽  
Vol 221 (2) ◽  
pp. 201-213 ◽  
Author(s):  
Jordana G A Coelho-Dos-Reis ◽  
Ryota Funakoshi ◽  
Jing Huang ◽  
Felipe Valença Pereira ◽  
Sho Iketani ◽  
...  

Abstract Background For the purpose of studying functional human dendritic cells (DCs) in a humanized mouse model that mimics the human immune system (HIS), a model referred to as HIS mice was established. Methods Human immune system mice were made by engrafting NOD/SCID/IL2Rgammanull (NSG) mice with human hematopoietic stem cells (HSCs) following the transduction of genes encoding human cytokines and human leukocyte antigen (HLA)-A2.1 by adeno-associated virus serotype 9 (AAV9) vectors. Results Our results indicate that human DC subsets, such as CD141+CD11c+ and CD1c+CD11c+ myeloid DCs, distribute throughout several organs in HIS mice including blood, bone marrow, spleen, and draining lymph nodes. The CD141+CD11c+ and CD1c+CD11c+ human DCs isolated from HIS mice immunized with adenoviruses expressing malaria/human immunodeficiency virus (HIV) epitopes were able to induce the proliferation of malaria/HIV epitopes-specific human CD8+ T cells in vitro. Upregulation of CD1c was also observed in human CD141+ DCs 1 day after immunization with the adenovirus-based vaccines. Conclusions Establishment of such a humanized mouse model that mounts functional human DCs enables preclinical assessment of the immunogenicity of human vaccines in vivo.


Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 617 ◽  
Author(s):  
Helen Freyberger ◽  
Yunxiu He ◽  
Amanda Roth ◽  
Mikeljon Nikolich ◽  
Andrey Filippov

A potential concern with bacteriophage (phage) therapeutics is a host-versus-phage response in which the immune system may neutralize or destroy phage particles and thus impair therapeutic efficacy, or a strong inflammatory response to repeated phage exposure might endanger the patient. Current literature is discrepant with regard to the nature and magnitude of innate and adaptive immune response to phages. The purpose of this work was to study the potential effects of Staphylococcus aureus phage K on the activation of human monocyte-derived dendritic cells. Since phage K acquired from ATCC was isolated around 90 years ago, we first tested its activity against a panel of 36 diverse S. aureus clinical isolates from military patients and found that it was lytic against 30/36 (83%) of strains. Human monocyte-derived dendritic cells were used to test for an in vitro phage-specific inflammatory response. Repeated experiments demonstrated that phage K had little impact on the expression of pro- and anti-inflammatory cytokines, or on MHC-I/II and CD80/CD86 protein expression. Given that dendritic cells are potent antigen-presenting cells and messengers between the innate and the adaptive immune systems, our results suggest that phage K does not independently affect cellular immunity or has a very limited impact on it.


Cytotherapy ◽  
2018 ◽  
Vol 20 (11) ◽  
pp. 1289-1308 ◽  
Author(s):  
CHARLOTTE DE Wolf ◽  
MARJA VAN DE BOVENKAMP ◽  
MARCEL HOEFNAGEL

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