Exonic single nucleotide polymorphisms within TLR3 associated with infant responses to serogroup C meningococcal conjugate vaccine |
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| Institution: | 1. Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK;2. Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;3. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK;1. Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia;2. Department of Medical Microbiology and Parasitology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia;3. Department of Medicine, Hospital Kota Bharu, Kota Bharu, Kelantan, Malaysia;4. Department of Paediatrics, Hospital Kota Bharu, Kota Bharu, Kelantan, Malaysia;5. Department of Medicine, Hospital Sungai Buloh, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia;6. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;7. Tropical Infectious Disease Research and Education Centre, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;1. Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States;2. University of Pennsylvania School of Medicine, Philadelphia, PA, United States;3. McMaster University, Ontario, Canada;1. Department of Biophysics, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India;2. Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India;3. Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, India;1. Oxford Vaccine Group, University of Oxford Department of Paediatrics, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford OX37LE, UK;1. Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;2. Department of Gastroenterology, The Third People’s Hospital of Wuxi, Wuxi 214041, Jiangsu, China;3. Public Health Clinical Center Affiliated to Fudan University, Shanghai 201508, China;4. Department of General Surgery, Wuxi Higher Health Vocational Technology School, Wuxi 214028, China;1. Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;2. IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain;3. Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain;4. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain;5. Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain;6. Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain |
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| Abstract: | The introduction of the serogroup C meningococcal (MenC) conjugate vaccination has successfully controlled the burden of disease associated with this serogroup in many countries. However, considerable inter-individual variation is observed in immune responses to MenC vaccine, and little is understood of the determinants of this variability. Previously, we reported an association between single nucleotide polymorphisms (SNPs) in TLR3 and CD44 and the persistence of MenC vaccine immunity. Here we further examine polymorphisms within these two candidate genes and immune responses to MenC vaccine. MenC-specific IgG concentrations and serum bactericidal assay (SBA) titres were measured one month after a primary course of MenC vaccination in 318 human infants. Tagging SNPs (TagSNPs) within TLR3 and CD44 were genotyped and regional imputations carried out to screen these genes for variations associated with immunological responses to MenC vaccine. This study reports an association between an exonic variant (rs3775290, P = 0.025) in TLR3 and MenC IgG concentrations, as well as an association between three SNPs in CD44 (rs3794109, P = 0.021; rs3794110, P = 0.022; rs112762, P = 0.049) and MenC SBA titres. These data support our previous findings of an association between SNPs in TLR3 and CD44, and present novel findings implicating exonic variants in these genes with MenC vaccine responses. |
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| Keywords: | Meningococcal vaccine Immunogenetics Toll-like receptors |
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