TY - JOUR
T1 - Dendritic cell-based immunotherapies to fight HIV
T2 - How far from a success story? a systematic review and meta-analysis
AU - Campos Coelho, Antonio Victor
AU - de Moura, Ronald Rodrigues
AU - Kamada, Anselmo Jiro
AU - da Silva, Ronaldo Celerino
AU - Guimarães, Rafael Lima
AU - Brandão, Lucas André Cavalcanti
AU - de Alencar, Luiz Cláudio Arraes
AU - Crovella, Sergio
PY - 2016/12/1
Y1 - 2016/12/1
N2 - The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%–51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogeni city, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.
AB - The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%–51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogeni city, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.
KW - Clinical trial
KW - Dendritic cell
KW - Human immunodeficiency virus
KW - Meta-regression
KW - Vaccine
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U2 - 10.3390/ijms17121985
DO - 10.3390/ijms17121985
M3 - Review article
AN - SCOPUS:85000809679
VL - 17
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 12
M1 - 1985
ER -