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

Raj Kurupati,Yan Li,Zhiquan Xiang,Hildegund Ertl,Qin Liu,Kenneth Schmader,Senthil Kannan,Susan Doyle,Andrew Kossenkov,Larissa Haut,Louise Showe

doi:10.18632/oncotarget.11704

Raj Kurupati, Yan Li + Show 9 more

Open Access

https://doi.org/10.18632/oncotarget.11704

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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.

Highlights

The efficacy and immunogenicity of vaccines varies depending on the study cohort
A study conducted in the US found significantly higher seroprevalence rates of antibodies to measles virus in African Americans compared to Caucasians [2] and antibody titers to the pertussis vaccine were strongly and consistently higher in African American children compared to Caucasian children [3]
When samples were stratified according to age, there was a bias of higher enrollment of African Americans into the younger (17 samples from African Americans, 95 samples from Caucasians) than the aged cohort (10 samples from African Americans, 150 samples from Caucasians, p-value by Fisher’s exact test = 0.022)

Summary

Introduction

The efficacy and immunogenicity of vaccines varies depending on the study cohort. Race and ethnicity were shown to affect antibody responses to the rubella vaccine, which elicited significantly higher titers in children of African ethnicity compared to those of European descent or Hispanic ethnicity [1]. A study conducted in the US found significantly higher seroprevalence rates of antibodies to measles virus in African Americans compared to Caucasians [2] and antibody titers to the pertussis vaccine were strongly and consistently higher in African American children compared to Caucasian children [3]. A similar study conducted in Northern Canada showed that native Innuit and Innu infants developed higher antibody titers to a measles vaccine as compared to those of Caucasian descent [4]. There is ample evidence that ethnicity affects responsiveness to a vaccine

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