The Application of Single-Cell RNA Sequencing in Vaccinology

Noé, Andrés; Cargill, Tamsin; Nielsen, Carolyn M.; Russell, Andrew J.; Barnes, Eleanor

doi:10.1155/2020/8624963

Cited by 36 publications

(17 citation statements)

References 176 publications

(223 reference statements)

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“…Delving further into the transcriptome of single-cells using RNA-seq is likely to reveal the fine-specificity of cellular events such as alternative splicing (i.e., splice variants) and allele-specific expression, and will also define the roles of new genes [ 46 , 146 ]. Detailed analysis of clonally-related antigen-specific T-cells using scRNA-seq provides information on pathways of differentiation of memory T-cells; using pseudotime tools, trajectories of T-cell differentiation can also be inferred [ 172 , 173 ]. These technologies have advanced substantially in the field of cancer immunology: vaccine research is just catching up.…”

Section: Measuring Vaccine-induced Cellular Responses In Humansmentioning

confidence: 99%

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

2021

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Pertussis (‘whooping cough’) is a severe respiratory tract infection that primarily affects young children and unimmunised infants. Despite widespread vaccine coverage, it remains one of the least well-controlled vaccine-preventable diseases, with a recent resurgence even in highly vaccinated populations. Although the exact underlying reasons are still not clear, emerging evidence suggests that a key factor is the replacement of the whole-cell (wP) by the acellular pertussis (aP) vaccine, which is less reactogenic but may induce suboptimal and waning immunity. Differences between vaccines are hypothesised to be cell-mediated, with polarisation of Th1/Th2/Th17 responses determined by the composition of the pertussis vaccine given in infancy. Moreover, aP vaccines elicit strong antibody responses but fail to protect against nasal colonisation and/or transmission, in animal models, thereby potentially leading to inadequate herd immunity. Our review summarises current knowledge on vaccine-induced cellular immune responses, based on mucosal and systemic data collected within experimental animal and human vaccine studies. In addition, we describe key factors that may influence cell-mediated immunity and how antigen-specific responses are measured quantitatively and qualitatively, at both cellular and molecular levels. Finally, we discuss how we can harness this emerging knowledge and novel tools to inform the design and testing of the next generation of improved infant pertussis vaccines.

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Section: Measuring Vaccine-induced Cellular Responses In Humansmentioning

confidence: 99%

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

2021

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“…Potential vaccine candidates are rapidly developed with the aid of computer-aided software/prescreening servers. Various types of vaccines have been designed through in silico approaches, i.e., COVID-19, Dengue, Cancer, Salmonella typhi, and Meningitis [133,134].…”

Section: Discussionmentioning

confidence: 99%

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

et al. 2022

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Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. AR has emerged due to the misuse and overuse of antimicrobial drugs, and few antibiotics are now left to deal with these superbug infections. To combat AR, vaccination is an effective method, used either therapeutically or prophylactically. In the current study, an in silico approach was applied for the design of multi-epitope-based vaccines against Providencia rettgeri, a major cause of traveler’s diarrhea. A total of six proteins: fimbrial protein, flagellar hook protein (FlgE), flagellar basal body L-ring protein (FlgH), flagellar hook-basal body complex protein (FliE), flagellar basal body P-ring formation protein (FlgA), and Gram-negative pili assembly chaperone domain proteins, were considered as vaccine targets and were utilized for B- and T-cell epitope prediction. The predicted epitopes were assessed for allergenicity, antigenicity, virulence, toxicity, and solubility. Moreover, filtered epitopes were utilized in multi-epitope vaccine construction. The predicted epitopes were joined with each other through specific GPGPG linkers and were joined with cholera toxin B subunit adjuvant via another EAAAK linker in order to enhance the efficacy of the designed vaccine. Docking studies of the designed vaccine construct were performed with MHC-I (PDB ID: 1I1Y), MHC-II (1KG0), and TLR-4 (4G8A). Findings of the docking study were validated through molecular dynamic simulations, which confirmed that the designed vaccine showed strong interactions with the immune receptors, and that the epitopes were exposed to the host immune system for proper recognition and processing. Additionally, binding free energies were estimated, which highlighted both electrostatic energy and van der Waals forces to make the complexes stable. Briefly, findings of the current study are promising and may help experimental vaccinologists to formulate a novel multi-epitope vaccine against P. rettgeri.

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“…Technologies depicting the Ig repertoire and evaluating the redundancy of clonal sequences have been found to be valuable in multiorgan diseases [ 96 ] but also in vaccination [ 97 ]. All these technologies are a real opportunity to characterize small cell populations and gene pathway implications, and to decipher the immune response in infectious disease and vaccines [ 98 ].…”

Section: High-throughput Immunomonitoring Techniquesmentioning

confidence: 99%

Strategies for Immunomonitoring after Vaccination and during Infection

et al. 2021

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Immunomonitoring is the study of an individual’s immune responses over the course of vaccination or infection. In the infectious context, exploring the innate and adaptive immune responses will help to investigate their contribution to viral control or toxicity. After vaccination, immunomonitoring of the correlate(s) and surrogate(s) of protection is a major asset for measuring vaccine immune efficacy. Conventional immunomonitoring methods include antibody-based technologies that are easy to use. However, promising sensitive high-throughput technologies allowed the emergence of holistic approaches. This raises the question of data integration methods and tools. These approaches allow us to increase our knowledge on immune mechanisms as well as the identification of key effectors of the immune response. However, the depiction of relevant findings requires a well-rounded consideration beforehand about the hypotheses, conception, organization and objectives of the immunomonitoring. Therefore, well-standardized and comprehensive studies fuel insight to design more efficient, rationale-based vaccines and therapeutics to fight against infectious diseases. Hence, we will illustrate this review with examples of the immunomonitoring approaches used during vaccination and the COVID-19 pandemic.

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The Application of Single-Cell RNA Sequencing in Vaccinology

Cited by 36 publications

References 176 publications

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

Strategies for Immunomonitoring after Vaccination and during Infection

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