Research

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14 pages, 1374 KiB

Open AccessArticle

Priming with Recombinant BCG Expressing HTI Enhances the Magnitude and Breadth of the T-Cell Immune Responses Elicited by MVA.HTI in BALB/c Mice

by Narcís Saubi, Athina Kilpeläinen, Yoshiki Eto, Chun-Wei Chen, Àlex Olvera, Tomáš Hanke, Christian Brander and Joan Joseph-Munné

Vaccines 2020, 8(4), 678; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8040678 - 13 Nov 2020

Cited by 4 | Viewed by 2529

Abstract

The use of Mycobacterium bovis bacillus Calmette–Guérin (BCG) as a live vaccine vehicle is a promising approach for HIV-1-specific T-cell induction. In this study, we used recombinant BCG expressing HIVACAT T-cell immunogen (HTI), BCG.HTI^2auxo.int. BALB/c mice immunization with BCG.HTI^2auxo.int prime [...] Read more.

The use of Mycobacterium bovis bacillus Calmette–Guérin (BCG) as a live vaccine vehicle is a promising approach for HIV-1-specific T-cell induction. In this study, we used recombinant BCG expressing HIVACAT T-cell immunogen (HTI), BCG.HTI^2auxo.int. BALB/c mice immunization with BCG.HTI^2auxo.int prime and MVA.HTI boost was safe and induced HIV-1-specific T-cell responses. Two weeks after boost, T-cell responses were assessed by IFN-γ ELISpot. The highest total magnitude of IFN-γ spot-forming cells (SFC)/10⁶ splenocytes was observed in BCG.HTI^2auxo.int primed mice compared to mice receiving MVA.HTI alone or mice primed with BCGwt, although the differences between the vaccination regimens only reached trends. In order to evaluate the differences in the breadth of the T-cell immune responses, we examined the number of reactive peptide pools per mouse. Interestingly, both BCG.HTI^2auxo.int and BCGwt primed mice recognized an average of four peptide pools per mouse. However, the variation was higher in BCG.HTI^2auxo.int primed mice with one mouse recognizing 11 peptide pools and three mice recognizing few or no peptide pools. The recognition profile appeared to be more spread out for BCG.HTI^2auxo.int primed mice and mice only receiving MVA.HTI. Here, we describe a useful vaccine platform for priming protective responses against HIV-1/TB and other prevalent infectious diseases. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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21 pages, 3572 KiB

Open AccessArticle

Revisiting CD8 T-cell ‘Memory Inflation’: New Insights with Implications for Cytomegaloviruses as Vaccine Vectors

by Rafaela Holtappels, Kirsten Freitag, Angelique Renzaho, Sara Becker, Niels A.W. Lemmermann and Matthias J. Reddehase

Vaccines 2020, 8(3), 402; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8030402 - 22 Jul 2020

Cited by 14 | Viewed by 3368

Abstract

Murine models of cytomegalovirus (CMV) infection have revealed an exceptional kinetics of the immune response. After resolution of productive infection, transient contraction of the viral epitope-specific CD8 T-cell pool was found to be followed by a pool expansion specific for certain viral epitopes [...] Read more.

Murine models of cytomegalovirus (CMV) infection have revealed an exceptional kinetics of the immune response. After resolution of productive infection, transient contraction of the viral epitope-specific CD8 T-cell pool was found to be followed by a pool expansion specific for certain viral epitopes during non-productive ‘latent’ infection. This phenomenon, known as ‘memory inflation’ (MI), was found to be based on inflationary KLRG1⁺CD62L⁻ effector-memory T cells (iTEM) that depend on repetitive restimulation. MI gained substantial interest for employing CMV as vaccine vector by replacing MI-driving CMV epitopes with foreign epitopes for generating high numbers of protective memory cells specific for unrelated pathogens. The concept of an MI-driving CMV vector is questioned by human studies disputing MI in humans. A bias towards MI in experimental models may have resulted from systemic infection. We have here studied local murine CMV infection as a route that is more closely matching routine human vaccine application. Notably, KLRG1⁻CD62L⁺ central memory T cells (TCM) and conventional KLRG1⁻CD62L⁻ effector memory T cells (cTEM) were found to expand, associated with ‘avidity maturation’, whereas the pool size of iTEM steadily declined over time. The establishment of high avidity CD8 T-cell central memory encourages one to pursue the concept of CMV vector-based vaccines. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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12 pages, 715 KiB

Open AccessArticle

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression

by Helal F. Hetta, Mohamed A. Mekky, Asmaa M. Zahran, Mohamed O. Abdel-Malek, Haidi K. Ramadan, Engy A. Shafik, Wael A. Abbas, Muhammad Abbas El-Masry, Nahed A. Mohamed, Amira A. Kamel, Najat Marraiki, Amany Magdy Beshbishy, Gaber El-Saber Batiha, Heba A. Osman, Gopala Koneru and Mohamed A. El-Mokhtar

Vaccines 2020, 8(3), 380; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8030380 - 11 Jul 2020

Cited by 18 | Viewed by 3352

Abstract

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of [...] Read more.

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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9 pages, 855 KiB

Open AccessArticle

CD19⁺ CD24^hi CD38^hi Regulatory B Cells and Memory B Cells in Periodontitis: Association with Pro-Inflammatory and Anti-Inflammatory Cytokines

by Helal F. Hetta, Ibrahim M. Mwafey, Gaber El-Saber Batiha, Suliman Y. Alomar, Nahed A. Mohamed, Maggie A. Ibrahim, Abeer Elkady, Ahmed Kh. Meshaal, Hani Alrefai, Dina M. Khodeer and Asmaa M. Zahran

Vaccines 2020, 8(2), 340; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8020340 - 26 Jun 2020

Cited by 21 | Viewed by 3509

Abstract

Regulatory B cells (Bregs) are unique subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Due to the current limitations of human Breg studies among periodontal diseases, in the present study, we tried to analyze the [...] Read more.

Regulatory B cells (Bregs) are unique subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Due to the current limitations of human Breg studies among periodontal diseases, in the present study, we tried to analyze the change in circulating Bregs, pro-inflammatory, and anti-inflammatory cytokines in patients with periodontitis. Peripheral blood from 55 patients with stage 2 periodontitis and 20 healthy controls was analyzed using flow cytometry to evaluate the frequency of CD19⁺CD24⁺CD38⁺ Breg cells. ELISA was used to assess the serum levels of the pro-inflammatory cytokines, including interleukins (IL)-1β, IL-6, TNF-α, and anti-inflammatory cytokines including IL-10, IL-35, and TGF-β. Increased proportions of Breg cells were observed in patients with stage 2 periodontitis compared to controls. Serum levels of cytokines were significantly higher in patients with periodontitis compared to controls. A significant positive correlation was observed between the frequencies of Breg cells and IL35 levels, IL10 levels, and TGF-β. In conclusion, our results suggest that the increase in peripheral Breg cells and serum cytokine levels among periodontitis patients seems to be closely associated with disease progression, a possible link between periodontitis, and systemic inflammatory process. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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Review

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24 pages, 1622 KiB

Open AccessReview

COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform

by Muhammad Umer Ashraf, Yeji Kim, Sunil Kumar, Dongyeob Seo, Maryam Ashraf and Yong-Soo Bae

Vaccines 2021, 9(2), 171; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9020171 - 18 Feb 2021

Cited by 46 | Viewed by 9059

Abstract

There are several emerging strategies for the vaccination of COVID-19 (SARS-CoV-2) however, only a few have yet shown promising effects. Thus, choosing the right pathway and the best prophylactic options in preventing COVID-19 is still challenging at best. Approximately, more than two-hundred vaccines [...] Read more.

There are several emerging strategies for the vaccination of COVID-19 (SARS-CoV-2) however, only a few have yet shown promising effects. Thus, choosing the right pathway and the best prophylactic options in preventing COVID-19 is still challenging at best. Approximately, more than two-hundred vaccines are being tested in different countries, and more than fifty clinical trials are currently undergoing. In this review, we have summarized the immune-based strategies for the development of COVID-19 vaccines and the different vaccine candidate platforms that are in clinical stages of evaluation, and up to the recently licensed mRNA-based COVID-19 vaccines of Pfizer-BioNtech and Moderna’s. Lastly, we have briefly included the potentials of using the ‘RPS-CTP vector system’ for the development of a safe and effective oral mucosal COVID-19 vaccine as another vaccine platform. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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20 pages, 1870 KiB

Open AccessReview

Immune Response to SARS-CoV-2 Infection in Obesity and T2D: Literature Review

by Jorge Pérez-Galarza, César Prócel, Cristina Cañadas, Diana Aguirre, Ronny Pibaque, Ricardo Bedón, Fernando Sempértegui, Hemmo Drexhage and Lucy Baldeón

Vaccines 2021, 9(2), 102; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9020102 - 29 Jan 2021

Cited by 23 | Viewed by 7483

Abstract

In December 2019, a novel coronavirus known as SARS-CoV-2 was first detected in Wuhan, China, causing outbreaks of the coronavirus disease COVID-19 that has now spread globally. For this reason, The World Health Organization (WHO) declared COVID-19 a public health emergency in March [...] Read more.

In December 2019, a novel coronavirus known as SARS-CoV-2 was first detected in Wuhan, China, causing outbreaks of the coronavirus disease COVID-19 that has now spread globally. For this reason, The World Health Organization (WHO) declared COVID-19 a public health emergency in March 2020. People living with pre-existing conditions such as obesity, cardiovascular diseases, type 2 diabetes (T2D), and chronic kidney and lung diseases, are prone to develop severe forms of disease with fatal outcomes. Metabolic diseases such as obesity and T2D alter the balance of innate and adaptive responses. Both diseases share common features characterized by augmented adiposity associated with a chronic systemic low-grade inflammation, senescence, immunoglobulin glycation, and abnormalities in the number and function of adaptive immune cells. In obese and T2D patients infected by SARS-CoV-2, where immune cells are already hampered, this response appears to be stronger. In this review, we describe the abnormalities of the immune system, and summarize clinical findings of COVID-19 patients with pre-existing conditions such as obesity and T2D as this group is at greater risk of suffering severe and fatal clinical outcomes. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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25 pages, 1864 KiB

Open AccessReview

B and T Cell Immunity in Tissues and Across the Ages

by Jayaum S. Booth and Franklin R. Toapanta

Vaccines 2021, 9(1), 24; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9010024 - 06 Jan 2021

Cited by 11 | Viewed by 6670

Abstract

B and T cells are key components of the adaptive immune system and coordinate multiple facets of immunity including responses to infection, vaccines, allergens, and the environment. In humans, B- and T-cell immunity has been determined using primarily peripheral blood specimens. Conversely, human [...] Read more.

B and T cells are key components of the adaptive immune system and coordinate multiple facets of immunity including responses to infection, vaccines, allergens, and the environment. In humans, B- and T-cell immunity has been determined using primarily peripheral blood specimens. Conversely, human tissues have scarcely been studied but they host multiple adaptive immune cells capable of mounting immune responses to pathogens and participate in tissue homeostasis. Mucosal tissues, such as the intestines and respiratory track, are constantly bombarded by foreign antigens and contain tissue-resident memory T (T_RM) cells that exhibit superior protective capacity to pathogens. Also, tissue-resident memory B (B_RM) cells have been identified in mice but whether humans have a similar population remains to be confirmed. Moreover, the immune system evolves throughout the lifespan of humans and undergoes multiple changes in its immunobiology. Recent studies have shown that age-related changes in tissues are not necessarily reflected in peripheral blood specimens, highlighting the importance of tissue localization and subset delineation as essential determinants of functional B and T cells at different life stages. This review describes our current knowledge of the main B- and T-cell subsets in peripheral blood and tissues across age groups. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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21 pages, 3551 KiB

Open AccessReview

Investigating Virological, Immunological, and Pathological Avenues to Identify Potential Targets for Developing COVID-19 Treatment and Prevention Strategies

by Zafar Mahmood, Hani Alrefai, Helal F. Hetta, Hidaya A. Kader, Nayla Munawar, Sheikh Abdul Rahman, Shereen Elshaer, Gaber EI-Saber Batiha and Khalid Muhammad

Vaccines 2020, 8(3), 443; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8030443 - 06 Aug 2020

Cited by 15 | Viewed by 8105

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus causing respiratory disease commonly known as COVID-19. This novel coronavirus transmits from human to human and has caused profound morbidity and mortality worldwide leading to the ongoing pandemic. Moreover, disease severity differs [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus causing respiratory disease commonly known as COVID-19. This novel coronavirus transmits from human to human and has caused profound morbidity and mortality worldwide leading to the ongoing pandemic. Moreover, disease severity differs considerably from individual to individual. Investigating the virology of COVID-19 and immunological pathways underlying its clinical manifestations will enable the identification and design of effective vaccines and potential therapies. In this review, we explore COVID-19 virology, the contribution of the immune system (innate and adaptive) during infection and control of the virus. Finally, we highlight vaccine development and implications of immune system modulation for potential therapeutic interventions to design better therapeutic strategies to guide future cure. Full article

(This article belongs to the Special Issue B and T Cell-Mediated Immunity)

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