Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells

Bowyer, Georgina; Sharpe, Hannah; Venkatraman, Navin; Ndiaye, Pierre Birahim; Wade, Djibril; Brenner, Nicole; Mentzer, Alexander J.; Mair, Catherine; Waterboer, Tim; Lambe, Teresa; Dieye, Tandakha N.; Mboup, Souleymane; Hill, Adrian V. S.; Ewer, Katie

doi:10.1084/jem.20200004

Cited by 33 publications

(38 citation statements)

References 75 publications

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“…Besides the high prevalence, the induced immune modulation and establishment of a periodically re-activated life-long latent infection marks CMV a very important viral infection ( 120 , 121 ). CMV infection typically distorts the T cell repertoire and overall phenotype by inducing a rapid differentiation and clonal expansion of CMV-specific CD8+ T cells.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the universal host immune phenotype, the negative effect of CMV infection on vaccine responses is most pronounced in the elderly ( 120 ). CMV sero-positive elderly adults have been reported to exhibit a decreased response to Influenza vaccine ( 127 , 128 ).…”

Section: Introductionmentioning

confidence: 99%

“…CMV sero-positive elderly adults have been reported to exhibit a decreased response to Influenza vaccine ( 127 , 128 ). A defective CD8+pSTAT1 and pSTAT3 pathway, expanding senescent CD57+KLG1+ T cell repertoire and the increasing TNF-α and IL-6 levels with infection duration, reduces cytokine responsiveness of vaccine-induced T-cells ( 120 , 128 , 129 ). Findings in younger CMV infected adults are conflicting.…”

Section: Introductionmentioning

confidence: 99%

“…An enhanced response, characterized by high levels of circulating Th1 and Th2 cytokines to Influenza vaccine is seen ( 127 ), possibly due to the cross-reactive CMV-specific CD8+ T-cell epitopes ( 130 ). Meanwhile, response to Ebola candidate vaccines, ChAd3 and MVA, is impaired ( 120 ).…”

Section: Introductionmentioning

confidence: 99%

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Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings

et al. 2021

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Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings

et al. 2021

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“…For example, the contribution of humoral and cellular responses to both influenza and RSV vaccination is altered in older compared to younger adults [102][103][104][105]. Contrastingly, CMV infection is associated with attenuated vaccine responses across age groups [106][107][108]. scRNA-seq is ideally placed to discover how these observations fit together, by profiling heterogeneous cell populations in detail.…”

Section: Comparing Vaccine Regimens Andmentioning

confidence: 99%

The Application of Single-Cell RNA Sequencing in Vaccinology

Noé

Cargill

Nielsen

et al. 2020

Journal of Immunology Research

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Single-cell RNA sequencing allows highly detailed profiling of cellular immune responses from limited-volume samples, advancing prospects of a new era of systems immunology. The power of single-cell RNA sequencing offers various opportunities to decipher the immune response to infectious diseases and vaccines. Here, we describe the potential uses of single-cell RNA sequencing methods in prophylactic vaccine development, concentrating on infectious diseases including COVID-19. Using examples from several diseases, we review how single-cell RNA sequencing has been used to evaluate the immunological response to different vaccine platforms and regimens. By highlighting published and unpublished single-cell RNA sequencing studies relevant to vaccinology, we discuss some general considerations how the field could be enriched with the widespread adoption of this technology.

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Indirect effects of cytomegalovirus infection: Implications for vaccine development

Moseley

Klenerman

Kadambari

2022

Reviews in Medical Virology

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Development of a cytomegalovirus (CMV) vaccine is a high priority due to its significant global impact-contributing to mortality in immunosuppressed individuals, neurodevelopmental delay in infected neonates and non-genetic sensorineural hearing loss. The impact of CMV on the general population has been less well studied; however, a wide range of evidence indicates that CMV may increase the risk of atherosclerosis, cancer, immunosenescence, and progression of tuberculosis (TB) and human immunodeficiency virus. Due to the high seroprevalence of CMV worldwide, any modulation of risk by CMV is likely to have a significant impact on the epidemiology of these diseases. This review will evaluate how CMV may cause morbidity and mortality outside of the neonatal and immunosuppressed populations and consider the potential impact of a CMV vaccine on these outcomes. | INTRODUCTIONCytomegalovirus (CMV) is the most common non-genetic cause of sensorineural hearing loss in neonates and a leading cause of neurodevelopmental delay. 1 In the immunocompromised host, CMV reactivation results in vasculopathy, graft rejection and severe end organ damage. 2,3 Subsequently, the development of a vaccine against CMV has been cited as a high priority for the last 2 decades including by the National Institute of Health. 4 CMV has been associated with several distinct disease processes-atherosclerosis, 5-8 cancer 9 and impaired immune response to vaccination. [10][11][12] Additionally, CMV is suspected to enhance the pathogenicity of human immunodeficiency virus (HIV) and tuberculosis (TB). [13][14][15][16] Animal studies and large population based epidemiological studies suggest that CMV may cause disease through mechanisms such as CD8+ memory T-cell inflation 17 ; immunosenescence and immunomodulation. [18][19][20] In addition, reactivation of CMV in local tissues may result in lytic replication and cause direct

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Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells

Cited by 33 publications

References 75 publications

Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings

Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings

The Application of Single-Cell RNA Sequencing in Vaccinology

Indirect effects of cytomegalovirus infection: Implications for vaccine development

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