Engagement of monocytes, NK cells, and CD4+ Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition.
PLoS Pathog
; 16(3): e1008377, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-32163525
ABSTRACT
The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. Similarly, an equivalent SIV-based ALVAC vaccine regimen decreased the risk of virus acquisition in Indian rhesus macaques of both sexes following intrarectal exposure to low doses of SIVmac251. Here, we demonstrate that the ALVAC-SIV/gp120/alum vaccine is also efficacious in female Chinese rhesus macaques following intravaginal exposure to low doses of SIVmac251 and we confirm that CD14+ classical monocytes are a strong correlate of decreased risk of virus acquisition. Furthermore, we demonstrate that the frequency of CD14+ cells and/or their gene expression correlates with blood Type 1 CD4+ T helper cells, α4ß7+ plasmablasts, and vaginal cytocidal NKG2A+ cells. To better understand the correlate of protection, we contrasted the ALVAC-SIV vaccine with a NYVAC-based SIV/gp120 regimen that used the identical immunogen. We found that NYVAC-SIV induced higher immune activation via CD4+Ki67+CD38+ and CD4+Ki67+α4ß7+ T cells, higher SIV envelope-specific IFN-γ producing cells, equivalent ADCC, and did not decrease the risk of SIVmac251 acquisition. Using the systems biology approach, we demonstrate that specific expression profiles of plasmablasts, NKG2A+ cells, and monocytes elicited by the ALVAC-based regimen correlated with decreased risk of virus acquisition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vagina
/
Vacinas Virais
/
Células Matadoras Naturais
/
Monócitos
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Vírus da Imunodeficiência Símia
/
Vacinação
/
Células Th1
/
Vacinas contra a SAIDS
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos