Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys.
Front Immunol
; 9: 2415, 2018.
Article
em En
| MEDLINE
| ID: mdl-30405615
ABSTRACT
Though immune correlates for protection are still under investigation, potent cytotoxic T lymphocyte responses are desirable for an ideal HIV-1 vaccine. PD-1 blockade enhances SIV-specific CD8+ T cells. However, little information has been reported about how it affects the immunogenicity and protection of prophylactic SIV vaccines in nonhuman primates. Here, we show that PD-1 blockade during vaccination substantially improved protective efficacy in SIV challenged macaques. The PD-1 pathway was blocked using a monoclonal antibody specific to human PD-1. Administration of this antibody effectively augmented and sustained vaccine-induced SIV-specific T cell responses for more than 42 weeks after first immunization in rhesus monkeys, as compared with SIV vaccination only. Importantly, after intrarectally repeated low-dosage challenge with highly pathogenic SIVmac239, monkeys with PD-1 blockade during vaccination achieved full protection against incremental viral doses of up to 50,000 TICD50. These findings highlight the importance of PD-1 blockade during vaccination for the development of HIV vaccines.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Síndrome de Imunodeficiência Adquirida dos Símios
/
HIV-1
/
Vírus da Imunodeficiência Símia
/
Vacinas contra a AIDS
/
Vacinas contra a SAIDS
/
Receptor de Morte Celular Programada 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China