Innate protection against intrarectal SIV acquisition by a live SHIV vaccine.
JCI Insight
; 9(12)2024 May 21.
Article
em En
| MEDLINE
| ID: mdl-38912579
ABSTRACT
Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Imunodeficiência Adquirida dos Símios
/
Vírus da Imunodeficiência Símia
/
Vacinas contra a SAIDS
/
Linfócitos T CD8-Positivos
/
Imunidade Inata
/
Macaca mulatta
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article