Transcriptional and Immunologic Correlates of Response to Pandemic Influenza Vaccine in Aviremic, HIV-Infected Children

Abstract

People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and ≥13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5, a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups.

Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial

“…Vaccine response was in fact extremely poor in our study compared to other series addressing also influenza immunization in children living with HIV ( 14 , 15 ). This fact is even more shocking taking into account the good immunological status of the children included in this pilot trial, as previous studies have suggested that immunological status determines vaccine response ( 7 , 32 ). The identification of predictors of vaccine response has been identified as an urgent need for this population that grows with the virus ( 32 ).…”

“…This fact is even more shocking taking into account the good immunological status of the children included in this pilot trial, as previous studies have suggested that immunological status determines vaccine response (7,32). The identification of predictors of vaccine response has been identified as an urgent need for this population that grows with the virus (32). Markers available to routine clinical practice would allow us to personalize vaccination schedules.…”

The role of cell-mediated immunity against influenza and its implications for vaccine evaluation

“…In addition, the difference in immune responses between LAIV and inactivated vaccines can also be explained at the level of gene expression ( 124 ). de Armas et al even suggested to use transcriptional data as a correlate of vaccine response in HIV-infected children ( 125 ). A recent study demonstrates that influenza vaccines are also able to epigenetically remodel cells of the innate immune system (monocytes and dendritic cells) which is associated with a higher expression of antiviral genes ( 126 ).…”

State-of-the-Science of human papillomavirus vaccination in women with human immunodeficiency Virus: Summary of a scientific workshop

“…In a cohort of perinatally infected children comparing treated and untreated patients, the number of memory B cells (cells that are recalled to proliferate and produce antibodies upon booster vaccination or re-exposure to pathogen) was not completely restored by ART ( McCarty et al, 2018 ), although this could improve through early initiation of ART ( Shalekoff et al, 2021 ). Reduced function of T follicular helper cells, which are critical for the differentiation of B cells into high-affinity antibody producers, correlates with poor response to an influenza vaccine in CWH who had undetectable HIV-1 virus ( de Armas et al, 2021 ). However, in CWH on antiretroviral treatment, the number of T follicular helper cells is partially restored ( McCarty et al, 2018 ).…”