The role of systems biology approaches in determining molecular signatures for the development of more effective vaccines

Pezeshki, Abdulmohammad; Ovsyannikova, Inna G.; McKinney, Brett A.; Kennedy, Richard B.

doi:10.1080/14760584.2019.1575208

Cited by 22 publications

(19 citation statements)

References 145 publications

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“…Despite the challenges facing research and development efforts, there is a critical need for personalized vaccines that can bolster immune responses in older adults and improve clinical outcomes [199–202]. In response to this demand for improved treatments among the aging population, vaccine formulations against influenza and HZ have been licensed for use despite an incomplete understanding of their mechanisms of action [28, 29, 177].…”

Section: Future Perspectivesmentioning

confidence: 99%

Immunosenescence and human vaccine immune responses

et al. 2019

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The age-related dysregulation and decline of the immune system—collectively termed “immunosenescence”—has been generally associated with an increased susceptibility to infectious pathogens and poor vaccine responses in older adults. While numerous studies have reported on the clinical outcomes of infected or vaccinated individuals, our understanding of the mechanisms governing the onset of immunosenescence and its effects on adaptive immunity remains incomplete. Age-dependent differences in T and B lymphocyte populations and functions have been well-defined, yet studies that demonstrate direct associations between immune cell function and clinical outcomes in older individuals are lacking. Despite these knowledge gaps, research has progressed in the development of vaccine and adjuvant formulations tailored for older adults in order to boost protective immunity and overcome immunosenescence. In this review, we will discuss the development of vaccines for older adults in light of our current understanding—or lack thereof—of the aging immune system. We highlight the functional changes that are known to occur in the adaptive immune system with age, followed by a discussion of current, clinically relevant pathogens that disproportionately affect older adults and are the central focus of vaccine research efforts for the aging population. We conclude with an outlook on personalized vaccine development for older adults and areas in need of further study in order to improve our fundamental understanding of adaptive immunosenescence.

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Section: Future Perspectivesmentioning

confidence: 99%

Immunosenescence and human vaccine immune responses

et al. 2019

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“…Exponential developments in the “OMIC” area has enabled further vaccine development and understanding of the immunological response and challenges surrounding this area ( 282 ). Systems vaccinology, which includes immunoformatics, DNA/RNAseq, microarrays, mass spectrometry proteomics, transcriptomics, and metabolomics have all shown huge potential in elucidating differences in vaccine strains, vaccine growth and individual response in depth and on an epigenetic level allowing the identification of new vaccine antigens with increased speed and sensitivity ( 235 , 263 , 283 – 285 ).…”

Section: Laboratory Determinants Of An Effective Immune Response To Mmentioning

confidence: 99%

Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

Connell

Leahy

et al. 2020

Front. Immunol.

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History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vaccinated individuals, demonstrating a benefit of this vaccine. Therefore, the question of what constitutes a good mumps vaccine and how its impact is assessed in this modern era remains to be addressed. Epidemiology of the individuals most affected by the outbreaks (predominantly young adults) and variance in the circulating MuV genotype have been well-described alluding to a collection of influences such as vaccine hesitancy, heterogeneous vaccine uptake, primary, and/or secondary vaccine failures. This review aims to discuss in detail the interplay of factors thought to be contributing to the current mumps outbreaks seen in highly vaccinated populations. In addition, how mumps diagnoses has progressed and impacted the understanding of mumps infection since a mumps vaccine was first developed, the limitations of current laboratory tests in confirming protection in vaccinated individuals and how vaccine effectiveness is quantified are also considered. By highlighting knowledge gaps within this area, this state-of-the-art review proposes a change of perspective regarding the impact of a vaccine in a highly vaccinated population from a clinical, diagnostic and public perspective, highlighting a need for a paradigm shift on what is considered vaccine immunity.

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“…Novel approaches include the study of high-dimensional cell-subset immunophenotyping through CyTOF (Porpiglia et al, 2017;Lingblom et al, 2018;Reeves et al, 2018) and vaccine-induced changes at the metabolic (Li et al, 2017) proteomic (Galassie and Link, 2015) genetic and transcriptional (Stubbington et al, 2017) levels. This knowledge is largely being harnessed to establish signatures predictive of vaccine immunogenicity (Pezeshki et al, 2019), although early inflammatory transcriptomic profiling has recently been explored in the context of vaccine safety (Tregoning et al, 2020). Systems serology has also been used to define Fc features associated with antibody transfer and effector function, as discussed previously (Chung and Alter, 2017;Jennewein et al, 2019) including a detailed characterization of adjuvant effects on antibody quality (Francica et al, 2017).…”

Section: Approaches To Close Our Gaps In Knowledge Methodologymentioning

confidence: 99%

Maternal Immunization: Nature Meets Nurture

Saso

Kampmann

2020

Front. Microbiol.

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Vaccinating women in pregnancy (i.e., maternal immunization) has emerged as a promising tool to tackle infant morbidity and mortality worldwide. This approach nurtures a 'gift of nature,' whereby antibody is transferred from mother to fetus transplacentally during pregnancy, or postnatally in breast milk, thereby providing passive, antigenspecific protection against infections in the first few months of life, a period of increased immune vulnerability for the infant. In this review, we briefly summarize the rationale for maternal immunization programs and the landscape of vaccines currently in use or in the pipeline. We then direct the focus to the underlying biological phenomena, including the main mechanisms by which maternally derived antibody is transferred efficiently to the infant, at the placental interface or in breast milk; important research models and methodological approaches to interrogate these processes, particularly in the context of recent advances in systems vaccinology; the potential biological and clinical impact of high maternal antibody titres on neonatal ontogeny and subsequent infant vaccine responses; and key vaccine-and host-related factors influencing the maternal-infant dyad across different environments. Finally, we outline important gaps in knowledge and suggest future avenues of research on this topic, proposing potential strategies to ensure optimal testing, delivery and implementation of maternal vaccination programs worldwide.

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The role of systems biology approaches in determining molecular signatures for the development of more effective vaccines

Cited by 22 publications

References 145 publications

Immunosenescence and human vaccine immune responses

Immunosenescence and human vaccine immune responses

Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

Maternal Immunization: Nature Meets Nurture

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