Characterizing Vaccine Responses Using Host Genomic and Transcriptomic Analysis

Department of Paediatrics, University of Oxford, Oxford, England, United Kingdom
Clinical Infectious Diseases (Impact Factor: 8.89). 05/2013; 57(6). DOI: 10.1093/cid/cit373
Source: PubMed


Vaccines have had a profound influence on human health with no other health intervention rivalling their impact on the morbidity and mortality associated with infectious disease. However, the magnitude and persistence of vaccine immunity varies considerably between individuals, a phenomenon that is not well understood. Recent studies have used contemporary technologies to correlate variation in the genome and transcriptome to immunological measures of vaccine responsiveness. These approaches have provided fresh insight into the intrinsic factors determining the potency and duration of vaccine-induced immunity. The fundamental challenge will be to translate these findings into innovative and pragmatic strategies to develop new and more effective vaccines.

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    • "However, two other studies of hepatitis B vaccine responses performed in young children showed much higher estimates of heritability of 91% (Yan et al., 2013) and 77% (Newport et al., 2004), respectively. In addition, responses to vaccines given at birth (oral polio vaccine [OPV] and Bacillus Calmette– Gué rin [BCG]) are more heritable than even those administered only 2 months later (diphtheria and tetanus) (Newport et al., 2004; O'Connor and Pollard, 2013). In addition, Evans et al. analyzed 12-year-old twins in Australia (Evans et al., 1999). "
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    ABSTRACT: There is considerable heterogeneity in immunological parameters between individuals, but its sources are largely unknown. To assess the relative contribution of heritable versus non-heritable factors, we have performed a systems-level analysis of 210 healthy twins between 8 and 82 years of age. We measured 204 different parameters, including cell population frequencies, cytokine responses, and serum proteins, and found that 77% of these are dominated (>50% of variance) and 58% almost completely determined (>80% of variance) by non-heritable influences. In addition, some of these parameters become more variable with age, suggesting the cumulative influence of environmental exposure. Similarly, the serological responses to seasonal influenza vaccination are also determined largely by non-heritable factors, likely due to repeated exposure to different strains. Lastly, in MZ twins discordant for cytomegalovirus infection, more than half of all parameters are affected. These results highlight the largely reactive and adaptive nature of the immune system in healthy individuals. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Jan 2015 · Cell
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    ABSTRACT: When oral vaccines are administered to children in lower- and middle-income countries, they do not induce the same immune responses as they do in developed countries. Although not completely understood, reasons for this finding include maternal antibody interference, mucosal pathology secondary to infection, malnutrition, enteropathy, and previous exposure to the organism (or related organisms). Young children experience a high burden of cholera infection, which can lead to severe acute dehydrating diarrhea and substantial mortality and morbidity. Oral cholera vaccines show variations in their duration of protection and efficacy between children and adults. Evaluating innate and memory immune response is necessary to understand V. cholerae immunity and to improve current cholera vaccine candidates, especially in young children. Further research on the benefits of supplementary interventions and delivery schedules may also improve immunization strategies.
    Preview · Article · May 2014 · Human Vaccines and Immunotherapeutics
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    ABSTRACT: Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such "systems vaccinology" approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity's diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations.
    Preview · Article · Aug 2014 · Proceedings of the National Academy of Sciences
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