Abstract
Vaccines have revolutionized public health, preventing millions of deaths each year, particularly in childhood.Yet, there is considerable variability in the magnitude and persistence of vaccine-induced immunity. Maintenance of specific antibody is essential for continuity of vaccine-induced serological protection. We conducted a genome-wide association study into the persistence of immunity to three childhood vaccines: capsular group C meningococcal (MenC), Haemophilus influenzae type b, and tetanus toxoid (TT) vaccines. We detail associations between variants in a locus containing a family of signal-regulatory proteins and the persistence MenC immunity. We postulate a regulatory role for the lead SNP, with supporting epigenetic and expression quantitative trait loci data. Furthermore, we define associations between SNPs in the human leukocyte antigen (HLA) locus and the persistence of TT-specific immunity. Moreover, we describe four classical HLA alleles, HLA DRB1∗0301, HLA DQB1∗0201, HLA DQB1∗0602, and HLA DRB1∗1501, associated with TT-specific immunity, independent of the lead SNP association.
Highlights
Vaccination will prevent an estimated 23.3 million deaths this decade (2011–2020) (Lee et al, 2013)
6.7 million SNPs were included in quantitative trait association analyses of four log10 normalized vaccine-induced immunological measures: MenC-specific immunoglobulin G (IgG) concentrations, MenC-specific serum bactericidal antibody (SBA) titers, Haemophilus influenzae type b (Hib) polyribosylribitol phosphate (PRP)-specific IgG concentrations, and tetanus toxoid (TT)-specific IgG concentrations
We present a statistical association between SNPs within a genomic region containing a family of signal-regulatory proteins (SIRPs, SIRPA, SIRPB, and SIRPG) and the persistence of MenC-specific SBA titers
Summary
Vaccination will prevent an estimated 23.3 million deaths this decade (2011–2020) (Lee et al, 2013). Polysaccharide-encapsulated organisms are the leading cause of bacterial meningitis and pneumonia in children. Haemophilus influenzae type b (Hib) and Neisseria meningitidis are estimated to cause 8.13 million and 500,000 serious illnesses worldwide each year, respectively (Watt et al, 2009; Wilder-Smith and Memish, 2003). Over 150,000 Hib and 50,000 meningococcal cases result in death each year (GBD 2013 Mortality and Causes of Death Collaborators, 2015). Tetanus is an acute and life-threatening disease, caused by the bacterium Clostridium tetani. An estimated 61,000 deaths resulted from neonatal tetanus in the year 2011 alone (World Health Organization, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
