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Transcriptomic profiling of rhesus macaques vaccinated with ALVAC-SIV/gp120 adjuvanted in Alum or MF59.

ABSTRACT: The Canarypox/gp120/Alum vaccines decreased the risk of HIV acquisition in humans. We demonstrate here the efficacy of this vaccine regimen also in the SIVmac251 macaque model when we used the alum but not the MF59 adjuvant. Analysis of innate and adaptive cell responses, envelope antibodies Fc profiles and glycoforms demonstrated a lower inflammatory response with alum than MF59. Alum elicited mucosal V2 peptide-specific IgG associated with vaccine efficacy whereas the MF59 induced mucosal V2 peptide-specific IgG associated with increased risk of infection. Alum modulated the expression of 12 genes, 7 of which are part of the RAS pathway, that correlates with vaccine efficacy and were linked to innate responses that preserve mucosal integrity and adaptive mucosal antibody response to V2. Thus, activation of the RAS pathway, preservation of mucosal integrity and mucosal antibody to V2 in concert, reduce the risk of SIVmac251 acquisition.

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE72624 | GEO | 2016/05/29

SECONDARY ACCESSION(S): PRJNA294508

REPOSITORIES: GEO

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Transcriptomic profiling of rhesus macaques vaccinated with ALVAC-SIV/gp120 adjuvanted in Alum or MF59.

Project description:The Canarypox/gp120/Alum vaccines decreased the risk of HIV acquisition in humans. We demonstrate here the efficacy of this vaccine regimen also in the SIVmac251 macaque model when we used the alum but not the MF59 adjuvant. Analysis of innate and adaptive cell responses, envelope antibodies Fc profiles and glycoforms demonstrated a lower inflammatory response with alum than MF59. Alum elicited mucosal V2 peptide-specific IgG associated with vaccine efficacy whereas the MF59 induced mucosal V2 peptide-specific IgG associated with increased risk of infection. Alum modulated the expression of 12 genes, 7 of which are part of the RAS pathway, that correlates with vaccine efficacy and were linked to innate responses that preserve mucosal integrity and adaptive mucosal antibody response to V2. Thus, activation of the RAS pathway, preservation of mucosal integrity and mucosal antibody to V2 in concert, reduce the risk of SIVmac251 acquisition. Fifty-four (54) rhesus macaques were randomized into two vaccination groups. One group (n=27) was primed twice with ALVAC-SIV (at week 0 and week 4) and boosted twice with ALVAC-SIV/gp120 in MF59 adjuvant (at week 12 and week 24). The second group (n=27) was primed twice with ALVAC-SIV (at week 0 and week 4) and boosted twice with ALVAC-SIV/gp120 in Alum adjuvant (at week 12 and week 24). Blood samples were taken pre-vaccination, 24 hours after the first prime (post-1st imunization at week 0) and 24 hours after the first boost (post-3rd immunization at week 12). All the samples were taken before SIV challenge. Blood samples were conserved in PAXgene tubes. RNA was extracted and hybridized to Illumina beadchips. technical replicate: P162_P382_post1st, P162_P382_post1st_rep1

2016-05-29 | E-GEOD-72624 | biostudies-arrayexpress

RNA-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine

Project description:We analyzed innate and adaptive immune responses elicited by the V1-deleted DNA/ALVAC/gp120/alum vaccine in non-human primates. Following SIVmac251 challenge exposure, we observed reduced risk of SIV acquisition comparing vaccinated animals to controls, confirming th ability of this vaccine strategy in decreasing the risk of SIV acquisition against vaginal exposure. Transcriptome and chromatin accessibility in CD14+ cells were analyzed by RNA-seq and ATAC-seq. Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway correlated with vaccine efficacy. The efficacy of V1-delted DNA/ALVAC/gp120/alum vaccine, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Our data support the protective role for CREB1 expression in monocytes and posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

2023-01-06 | GSE189032 | GEO

ATAC-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine [study 2]

2023-01-06 | GSE188879 | GEO

Transcription profiling of mouse muscle tissue after in-vivo intramuscularly administration of MF59, CpG, MF59+CpG, alum and PBS

Project description:Analysis of whole mouse muscle gene expression signature induced by in-vivo intramuscularly administration of MF59, CpG, MF59+CpG, alum and PBS. MF59 and alum are licensed human vaccine adjuvants; CpG is a TLR-agonist adjuvant.

2009-07-03 | E-TABM-506 | biostudies-arrayexpress

Transcriptional profiling of macaques treated with ALVAC- and NYVAC-SIV+gp120 alum vaccines

Project description:We compare the immunogenicity of ALVAC- or NYVAC- based SIVmac251 vaccine regimens combined with gp120/alum boosts and their relative efficacy in a cohort of 65 female rhesus macaques. Both NYVAC- and ALVAC-based regimens induced equivalent titers of serum binding antibodies to gp120, whereas NYVAC elicited significantly higher envelope specific T cell responses. Surprisingly, however, only the ALVAC-based regimen was able to significantly decrease the risk of SIVmac251 acquisition following repeated low-dose intravaginal challenges. The risk of virus acquisition was associated negatively with the frequency of classical monocytes and positively with non-classical. The systems biology approach used to investigate the molecular basis of the different vaccine efficacies demonstrated specific expression profiles elicited by the ALVAC-based regimen that correlate with efficacy.

2020-03-05 | GSE138195 | GEO

Transcriptomic profiling of rhesus macaques vaccinated with Ad26/ALVAC+gp120 or DNA/ALVAC+gp120

Project description:We contrasted innate and adaptive immune responses of HIV vaccine candidates of varying efficacy in macaques that shared the ALVAC+gp120 protein boost with an ALVAC, DNA or Ad26 prime modality. The vaccine efficacies of the DNA/ALVAC+gp120 and ALVAC/ALVAC+gp120 vaccine regimens, both protective, were associated with qualitative temporal-spatial differences in the innate CD14+ and CD16+ cells in blood and tissues. The activation of hypoxia and the inflammasome in CD14+ DR+ CD16- classical monocytes and CD4+ Th2 responses correlated with a decreased risk of SIVmac251 acquisition. CD4+ Th2 cells, in turn, correlated with mucosal NKp44+ cells and mucosal protective antibodies to V2. In contrast, the Ad26/ALVAC+gp120 vaccine resulted in increased de novo differentiated CX3CR1+ CD163+ macrophages in lymph nodes, increased CD4+ Th17 cells in blood and rectal mucosa, and a lack vaccine efficacy. These data posit that the engagement of classical monocytes and inflammasome activation is central for the elicitation of protective innate and adaptive responses by the ALVAC-based HIV vaccine platform.

2018-02-23 | GSE108011 | GEO

MF59 and Pam3CSK4 boost adaptive responses to influenza subunit vaccine through an IFN type I independent mechanism of action

Project description:Analysis of whole mouse muscle and inguinal lymph node gene expression signature induced after 6h by in-vivo intramuscularly administration of MF59, alum, CpG, resiquimod (R848), Pam3CSK4 and DMSO and PBS controls. Analysis of splenocyte gene expression signature induced by the same treatments after 6h of incubation. MF59 and alum are licensed human vaccine adjuvants; CpG is a TLR9-agonist adjuvant; resiquimod (R848) is a TLR7/8-agonist adjuvant and Pam3CSK4 is a TLR2-agonist adjuvant.

2012-02-22 | E-MTAB-942 | biostudies-arrayexpress

Passive Transfer of Vaccine-Elicited Antibodies Protects Against SIV in Rhesus Macaques

Project description:In this study, we show that passive transfer of purified antibodies from vaccinated macaques can protect naïve animals against SIVmac251 challenges. The protective signature included multiple antibody functions and correlated with upregulation of interferon pathways in the vaccinated animals. Adoptive transfer of purified IgG from the vaccinated animals with the most robust protective signatures provided partial protection against SIVmac251 challenges in naïve recipient rhesus macaques. These data demonstrate the protective efficacy of purified vaccine-elicited antiviral antibodies, even in the absence of virus neutralization.

2020-08-14 | GSE156177 | GEO

Transcriptomic profiling of young and old rhesus macaques vaccinated with DNA/ALVAC+gp120

Project description:The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to the virus. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Central to vaccine efficacy is the engagement of the CCR2+/CCL2 axis and tolerogenic dendritic cells producing IL-10 (DC-10). Durable epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway and increased levels of miRNA-139-5p, a negative regulator of expression of the cAMP-specific phosphodiesterase PDE4D, in extracellular vesicles correlated with vaccine efficacy. These data posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

2022-12-28 | GSE188901 | GEO

Gene expression profiling of rhesus macaques vaccinated with ALVAC-SIVgpe DNA + SIVgp120 protein subunit and unvaccinated controls after challenge with SIVmac251 - 3 wks post-infection

Project description:The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans. A total of 31 RNA samples were hybridized on to Rhesus Affymetrix 3' Expression arrays. The study was composed of 8 vaccinated and 10 control animals subjected to a low dose challenge and 6 vaccinated and 7 control animals subjected to a high dose challenge

2013-03-01 | E-GEOD-37311 | biostudies-arrayexpress

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