• Clinical and Experimental Vaccine Research
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• v.13 no.1
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• pp.10-20
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• 2024

Animal models are essential in medical research for testing drugs and vaccines. These models differ from humans in various respects, so their results are not directly translatable in humans. To address this issue, humanized mice engrafted with functional human cells or tissue can be helpful. We propose using humanized mice that support the engraftment of human hematopoietic stem cells (HSCs) without irradiation to evaluate vaccines that influence patient immunity. For infectious diseases, several types of antigens and adjuvants have been developed and evaluated for vaccination. Peptide vaccines are generally used for their capability to fight cancer and infectious diseases. Evaluation of adjuvants is necessary as they induce inflammation, which is effective for an enhanced immune response but causes adverse effects in some individuals. A trial can be done on humanized mice to check the immunogenicity of a particular adjuvant and peptide combination. Messenger RNA has also emerged as a potential vaccine against viruses. These vaccines need to be tested with human immune cells because they work by producing a particular peptide of the pathogen. Humanized mice with human HSCs that can produce both myeloid and lymphoid cells show a similar immune response that these vaccines will produce in a patient.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.10.1-10.16
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• 2023

Memory T (Tm) cells protect against Ags that they have previously contacted with a fast and robust response. Therefore, developing long-lived Tm cells is a prime goal for many vaccines and therapies to treat human diseases. The remarkable characteristics of Tm cells have led scientists and clinicians to devise methods to make Tm cells more useful. Recently, Tm cells have been highlighted for their role in coronavirus disease 2019 vaccines during the ongoing global pandemic. The importance of Tm cells in cancer has been emerging. However, the precise characteristics and functions of Tm cells in these diseases are not completely understood. In this review, we summarize the known characteristics of Tm cells and their implications in the development of vaccines and immunotherapies for human diseases. In addition, we propose to exploit the beneficial characteristics of Tm cells to develop strategies for effective vaccines and overcome the obstacles of immunotherapy.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.51-57
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• 2015

Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.

• Clinical and Experimental Vaccine Research
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• v.12 no.3
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• pp.193-208
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• 2023

One of the most significant medical advancements in human history is the development of vaccines. Progress in vaccine development has always been greatly influenced by scientific human innovation. The main objective of vaccine development would be to acquire sufficient evidence of vaccine effectiveness, immunogenicity, safety, and/or quality to support requests for marketing approval. Vaccines are biological products that enhance the body's defenses against infectious diseases. From the first smallpox vaccine to the latest notable coronavirus disease 2019 nasal vaccine, India has come a long way. The development of numerous vaccines, driven by scientific innovation and advancement, combined with researcher's knowledge, has helped to reduce the global burden of disease and mortality rates. The Drugs and Cosmetics Rules of 1945 and the New Drugs and Clinical Trials Rules of 2019 specify the requirements and guidelines for CMC (chemistry, manufacturing, and controls) for all manufactured and imported vaccines, including those against coronavirus infections. This article provides an overview of the regulation pertaining to the development process, registration, and approval procedures for vaccines, particularly in India, along with their brief history.

• IMMUNE NETWORK
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• v.4 no.3
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• pp.131-142
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• 2004

In recent years, adjuvants have received much attention because of the development of purified subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. Therefore, immunologic adjuvants have been developed and testing for most of this century. During the last years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS-21, MF-59 and immunostimulating complexes (ISCOMS). Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. The most common adjuvants for human use today are aluminum hydroxide and aluminum phosphate. Calcium phosphate and oil emulsions have been also used in human vaccination. The biggest issue with the use of adjuvants for human vaccines is the toxicity and adverse side effects of most of the adjuvant formulations. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.

• Journal of Microbiology and Biotechnology
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• v.28 no.12
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• pp.2113-2120
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• 2018

Cross-reactive material 197 ($CRM_{197}$) is a non-toxic mutant of diphtheria toxin containing a single amino acid substitution of glycine 52 with glutamic acid. $CRM_{197}$ has been used as a carrier protein for poorly immunogenic polysaccharide antigens to improve immune responses. In this study, to develop a sandwich ELISA that can detect $CRM_{197}$ and $CRM_{197}$ conjugate vaccines, we generated a human anti-$CRM_{197}$ monoclonal antibody (mAb) 3F9 using a phage-displayed human synthetic Fab library and produced mouse anti-$CRM_{197}$ polyclonal antibody. The affinity ($K_D$) of 3F9 for $CRM_{197}$ was 3.55 nM, based on Bio-Layer interferometry, and it bound specifically to the B fragment of $CRM_{197}$. The sandwich ELISA was carried out using 3F9 as a capture antibody and the mouse polyclonal antibody as a detection antibody. The detection limit of the sandwich ELISA was <1 ng/ml $CRM_{197}$. In addition, the 3F9 antibody bound to the $CRM_{197}$-polysaccharide conjugates tested in a dose-dependent manner. This ELISA system will be useful for the quantification and characterization of $CRM_{197}$ and $CRM_{197}$ conjugate vaccines. To our knowledge, this study is the first to generate a human monoclonal antibody against $CRM_{197}$ and to develop a sandwich ELISA for $CRM_{197}$ conjugate vaccines.

• IMMUNE NETWORK
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• v.21 no.1
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• pp.4.1-4.18
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• 2021

The global outbreak of coronavirus disease 2019 (COVID-19) is still threatening human health, economy, and social life worldwide. As a counteraction for this devastating disease, a number of vaccines are being developed with unprecedented speed combined with new technologies. As COVID-19 vaccines are being developed in the absence of a licensed human coronavirus vaccine, there remain further questions regarding the long-term efficacy and safety of the vaccines, as well as immunological mechanisms in depth. This review article discusses the current status of COVID-19 vaccine development, mainly focusing on antigen design, clinical trials in later stages, and immunological considerations for further study.

• Clinical and Experimental Vaccine Research
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• v.13 no.1
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• pp.21-27
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• 2024

Chronic infectious diseases refer to diseases that require a long period of time from onset to cure or death, the use of therapeutic vaccines has recently emerged to eradicate diseases. Currently, clinical research is underway to develop therapeutic vaccines for chronic infectious diseases based on various vaccine formulations, and the recent success of the messenger RNA vaccine platform and efforts to apply it to therapeutic vaccines are having a positive impact on conquering chronic infectious diseases. However, since research on the development of therapeutic vaccines is still relatively lacking compared to prophylactic vaccines, there is a need to focus more on the development of therapeutic vaccines to overcome threats to human health caused by chronic infectious diseases. In order to accelerate the development of therapeutic vaccines for chronic infectious diseases in the future, it is necessary to establish a clear concept of therapeutic vaccines suitable for the characteristics of each chronic infectious disease, as well as standardize vaccine effectiveness evaluation methods, secure standards/reference materials, and simplify the vaccine approval procedure.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.sup1
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• pp.72-76
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• 2009

Rotavirus infection is the leading cause of severe diarrhea disease in infants and young children worldwide. Rotavirus infects every child at least once by her/his $5^{th}$ birthday. It has been known that single episode of rotavirus infection can protect or alleviate subsequent illness caused by both homotypic and heterotypic rotaviruses. There are two currently licensed rotavirus vaccines. One is human-bovine rotavirus reassortant pentavalent vaccine ($RotaTeq^{TM}$), which contains five reassortant rotavirus (expressing protein G1, G2, G3, G4 and P[8]) and was licensed in Korea for use among infants in 2007. Another is live-attenuated human rotavirus vaccine ($Rotarix^{TM}$) derived from 89-12 strain which represents the most common of the human rotavirus VP7(G1) and VP4(P[8]) antigens. $Rotarix^{TM}$ was licensed in Korea in 2008. Both live oral rotavirus vaccines are efficacious in preventing severe rotavirus gastroenteritis.

• IMMUNE NETWORK
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• v.21 no.1
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• pp.5.1-5.22
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• 2021

Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette-Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.