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Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy

Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy
  • Host genetics contributes to the effectiveness of dendritic cell-based HIV

Fonte

Europe PubMed Central

PubMed Central

Taylor & Francis

Autoria

Edione C. Reis, Lais T. da Silva, Wanessa C. da Silva, Alexandre Rios, Alberto J. Duarte, Telma M. Oshiro, Sergio Crovella, Alessandra Pontillo

Resumo

Systems biological analysis has recently revealed how innate immune variants as well as gut microbiota
impact the individual response to immunization. HIV-infected (HIVC) patients have a worse response rate
after standard vaccinations, possibly due to the immune exhaustion, increased gut permeability and
microbial translocation. In the last decade, dendritic cells (DC)-based immunotherapy has been proposed
as an alternative approach to control HIV plasma viral load, however clinical trials showed a heterogeneity
of immunization response.
Hypothesizing that host genetics may importantly affects the outcome of immunotherapy in HIVC
patients, genetic polymorphisms’ distribution and gene expression modulation were analyzed in a phase
I/II clinical trial of DC-based immunotherapy according to immunization response, and quality of vaccine
product (DC).
Polymorphisms in genes previously associated with progression of HIV infection to AIDS (i.e.: PARD3B,
CCL5) contribute to a better response to immunotherapy in HIVC individuals, possibly through a systemic
effect on host immune system, but also directly on vaccine product.
Genes expression profile after immunization correlates with different degrees of immune chronic
activation/exhaustion of HIVC patients (i.e. PD1, IL7RA, EOMES), but also with anti-viral response and DC
quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an immunocompetent individual would have a better
vaccine response.
These findings showed once more that host genetics can affect the response to DC-based
immunotherapy in HIVC individuals, contributing to the heterogeneity of response observed in concluded
trials; and it can be used as predictor of immunization success.

 

Host genetics contributes to the effectiveness of dendritic cell-based HIV

 

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