The genetic basis for interindividual immune response variation to measles vaccine: New understanding and new vaccine approaches
Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA. Expert Review of Vaccines
(Impact Factor: 4.21).
01/2013; 12(1):57-70. DOI: 10.1586/erv.12.134
The live-attenuated measles vaccine is effective, but measles outbreaks still occur in vaccinated populations. This warrants elucidation of the determinants of measles vaccine-induced protective immunity. Interindividual variability in markers of measles vaccine-induced immunity, including neutralizing antibody levels, is regulated in part by host genetic factor variations. This review summarizes recent advances in our understanding of measles vaccine immunogenetics relative to the perspective of developing better measles vaccines. Important genetic regulators of measles vaccine-induced immunity, such as HLA class I and HLA class II genotypes, single nucleotide polymorphisms in cytokine/cytokine receptor genes (IL12B, IL12RB1, IL2, IL10) and the cell surface measles virus receptor CD46 gene, have been identified and independently replicated. New technologies present many opportunities for identification of novel genetic signatures and genetic architectures. These findings help explain a variety of immune response-related phenotypes and promote a new paradigm of 'vaccinomics' for novel vaccine development.
Available from: January Weiner
- "Papillomavirus and smallpox vaccines induce similar inflammatory and IFN signatures [39,40], as well as cytokine production and genes associated with cytotoxicity and cell cycle pathways. Recent advances in measles vaccine immunogenetics are covered in detail by Haralambieva et al. . Not all individuals respond equally well to the same vaccine. "
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ABSTRACT: The immune system has evolved complex and specialized mechanisms to mount specific defense responses against the various types of pathogens it encounters. For the development of new vaccines, it is crucial to gain a better understanding of what these mechanisms are and how they work. The field of vaccinology has adopted high-throughput profiling techniques to gain more detailed insights into the various immune responses elicited by different vaccines and natural infections. From all detailed transcriptional profiles generated today, a general picture of immunological responses emerges. First, almost every type of vaccine induces an early interferon-dominated signature. Second, different vaccine formulations induce distinct transcriptional signatures, representing the highly specialized defense mechanisms that must cope with the different pathogens and insults they cause. Transcriptional profiling has shifted its attention toward early molecular signatures, with a growing awareness that early innate responses are likely critical instructors for the development of adaptive immunity at later time points.
Copyright © 2015. Published by Elsevier Ltd.
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ABSTRACT: Most people with hepatitis C virus (HCV) develop chronic infection with persistent viremia. Resolution of infection is associated with antiviral cellular immune responses of T helper 1 (Th1) type. Interleukin-12 (IL-12) is a key cytokine in the generation of Th1 responses, and functionally relevant polymorphisms of the IL12B gene and its promoter have been described recently. We sought an association between three IL12B polymorphisms and outcome of HCV infection in 195 HCV antibody-positive patients; 123 were chronically infected with detectable HCV RNA, and 72 had spontaneously resolved infection testing repeatedly negative for HCV RNA. Genotyping was performed for a single nucleotide polymorphism (SNP) in the 3'-UTR (1188A/C) of the IL12B gene and for 4-bp insertion/deletion polymorphisms in the IL12B promoter region and in the intron 4 region of the IL12B gene. We found chronically infected patients were significantly more likely than those with resolved HCV infection to be homozygous for the 3'-UTR A allele (66% vs. 50%; chi-square = 4.12, p = 0.04 with Yates correction), which has been associated with lower IL-12 production. No other significant association was found. Our findings support the concept that an individual's genetically determined ability to produce IL-12 is another factor that can influence the outcome of HCV infection.
Available from: Sonia Radice
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