Susceptibility to Simian immunodeficiency virus ex vivo predicts outcome of a prime-boost vaccine after SIVmac239 challenge.
J Acquir Immune Defic Syndr
; 52(2): 162-9, 2009 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-19644382
ABSTRACT
BACKGROUND:
Efficacy assessment of AIDS vaccines relies both on preclinically challenging immunized monkeys with simian immunodeficiency virus (SIV) or monitoring infection rates in large human trials. Although conventional parameters of vaccine-induced immune responses do not completely predict outcome, existing methods for testing cellular immunity are sophisticated and difficult to establish in resource-limited settings.METHODS:
We have used virus replication kinetics (VVR) on ConA-stimulated peripheral blood mononuclear cells from rhesus monkeys immunized with DNA replication-defective adenovirus vector expressing various SIV genes, as an ex vivo model, to mimic the effects of different immune effector functions on viral infection.RESULTS:
VVR was attenuated by the immunization and correlated 2 weeks after first boost, with the number of interferon gamma-secreting cells and T-cell noncytotoxic antiviral responses. Importantly, VVR on the day of challenge but not interferon gamma responses correlated with viremia and with memory CD4+ T-cell measurements after SIVmac239 challenge. Similarly, T-cell noncytotoxic antiviral responses on the day of challenge correlated directly with memory CD4 T cell and inversely with plasma viremia after challenge.CONCLUSIONS:
VVR thus served as a better predictor of protective capacity of the vaccine regimen in these monkeys. We suggest that VVR be considered in the evaluation of candidate AIDS vaccines in humans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Imunodeficiência Adquirida dos Símios
/
Vírus da Imunodeficiência Símia
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Vacinas contra a SAIDS
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Técnicas de Laboratório Clínico
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Avaliação Pré-Clínica de Medicamentos
Tipo de estudo:
Diagnostic_studies
/
Evaluation_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article