Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct pre-vaccination gene expression profiles in blood

Abstract

// Raj Kurupati 1,* , Andrew Kossenkov 1,* , Larissa Haut 1 , Senthil Kannan 1,2 , Zhiquan Xiang 1 , Yan Li 1 , Susan Doyle 3 , Qin Liu 1 , Kenneth Schmader 3 , Louise Showe 1 and Hildegund Ertl 1 1 The Wistar Institute, Philadelphia, PA, USA 2 Biomedical Graduate Group, University of Pennsylvania, Philadelphia, PA, USA 3 Development and Division of Geriatrics, GRECC, Durham VA Medical Center and Center for the Study of Aging and Human, Department of Medicine, Duke University Medical Center, Durham, NC, USA * These authors have contributed equally to this work Correspondence to: Hildegund Ertl, email: // Keywords : B cell responses, inactivated influenza vaccine, race, Immunology and Microbiology Section, Immune response, Immunity Received : June 17, 2016 Accepted : August 25, 2016 Published :August 30, 2016 Abstract We conducted a 5-year study analyzing antibody and B cell responses to the influenza A virus components of the inactivated influenza vaccine, trivalent (IIV3) or quadrivalent (IIV4) in younger (aged 35-45) and aged (≥65 years of age) Caucasian and African American individuals. Antibody titers to the two influenza A virus strains, distribution of circulating B cell subsets and the blood transcriptome were tested at baseline and after vaccination while expression of immunoregulatory markers on B cells were analyzed at baseline. African Americans mounted higher virus neutralizing and IgG antibody responses to the H1N1 component of IIV3 or 4 compared to Caucasians. African Americans had higher levels of circulating B cell subsets compared to Caucasians. Expression of two co-regulators, i.e., programmed death (PD)-1 and the B and T cell attenuator (BTLA) were differentially expressed in the two cohorts. Race-related differences were caused by samples from younger African Americans, while results obtained with samples of aged African Americans were similar to those of aged Caucasians. Gene expression profiling by Illumina arrays revealed highly significant differences in 1368 probes at baseline between Caucasians and African Americans although samples from both cohorts showed comparable changes in transcriptome following vaccination. Genes differently expressed between samples from African Americans and Caucasians regardless of age were enriched for myeloid genes, while the transcripts that differed in expression between younger African Americans and younger Caucasians were enriched for those specific for B-cells.