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The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in non-human primates

ABSTRACT: The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in non-human primates

PROVIDER: PRJNA1234651 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32654919.fastq.gz	Fastqsanger.gz
	SRR32654920.fastq.gz	Fastqsanger.gz
	SRR32654921.fastq.gz	Fastqsanger.gz
	SRR32654922.fastq.gz	Fastqsanger.gz
	SRR32654923.fastq.gz	Fastqsanger.gz

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The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in non-human primates

Project description:The induction of durable protective immune responses is the main goal of prophylactic vaccines, and adjuvants play an important role as drivers of such responses. Despite advances in vaccine strategies, a safe and effective HIV vaccine remains a significant challenge. The use of an appropriate adjuvant is crucial to the success of HIV vaccines. Here, we assessed the saponin/MPLA nanoparticle (SMNP) adjuvant with an HIV envelope (Env) trimer, evaluating the impact of adjuvant dose on the establishment of Env-specific memory B cell responses in non-human primates.

2025-03-11 | GSE291681 | GEO

scRNA-seq profiling of lymph node activation in non-human primate Rhesus macaques by aluminum hydroxide and saponin adjuvant SMNP

Project description:Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Using a stabilized HIV envelope trimer as a model immunogen, we carried out studies in non-human primates (NHPs), comparing the most common clinical adjuvant alum and Saponin/MPLA Nanoparticles (SMNP), a novel ISCOMs-like adjuvant. SMNP elicited substantially stronger humoral immune responses than alum and induced strong type I interferon transcriptional signatures, expansion of innate immune cells, and increased antigen presenting cell activation in LNs. These findings indicate that SMNP promotes multiple facets of the early immune response relevant for enhanced immunity to vaccination.

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Mechanism of activation of porcine dendritic cells by an alpha-D-glucan nanoparticle adjuvant and nanoparticle/poly(I:C) combination adjuvant.

Project description:Mechanism of activation of porcine dendritic cells by an alpha-D-glucan nanoparticle adjuvant and nanoparticle/poly(I:C) combination adjuvant.

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Peripheral blood transcriptomics following immunization with TLR-adjuvanted nanoparticle vaccine in rhesus macaques

Project description:Transmission-blocking vaccines (TBVs) aim to disrupt malaria parasite development by targeting antigens expressed in the mosquito midgut and are considered an integral element of malaria eradication efforts. Here, we used non-human primates to demonstrate that immune responses to Pfs25, the leading TBV candidate, can be improved using unconjugated Pfs25 encapsulated in PLGA-based synthetic vaccine particles (SVP[Pfs25]) delivered subcutaneously, compared to the multimeric form, Pfs25-EPA administered intramuscularly. Pfs25-EPA given with the toll-like receptor (TLR)-based adjuvant GLA-LSQ induced robust Ab responses, but SVP[Pfs25] adjuvanted with GLA-LSQ or SVPs containing CpG or R848 increased Ab titers, Pfs25-specific plasmablasts, circulating memory B cells, and plasma cells in the bone marrow. Animals receiving R848 or CpG showed particularly strong type I IFN polarized innate activation, which correlated with increased Ab half-life. Only SVP[Pfs25] induced detectable Pfs25-specific CD4 Th1 and Tfh cells, correlating with improved Ab avidity. Collectively, multiple aspects of the responses elicited to Pfs25 indicate that the nanoparticle technology combined with TLR agonists is a promising platform for TBVs.

2017-08-23 | GSE102909 | GEO

A TLR7-nanoparticle adjuvant promotes broad immune responses against heterologous strains of Influenza and SARS-CoV-2

Project description:Effective vaccines against viruses such as Influenza and SARS-CoV-2 must elicit a diverse repertoire of antibodies against multiple variant virus strains. However, antibody responses to current vaccines often lack cross-reactivity due to immunodominance. Here, we describe the synthesis of a toll-like receptor 7 agonist (TLR7)-nanoparticle adjuvant, TLR7-NP, constructed from TLR7 agonist-initiated ring-opening polymerization of lactide and self-assembly with poly(ethylene glycol)-b-poly(lactic-co-glycolic acid). TLR7-NP can enhance lymph node targeting, leading to persistent activation of immune cells. When mixed with Alum-adsorbed antigens, this TLR7-NP adjuvant elicited cross-reactive antibodies for both dominant and subdominant epitopes, as well as antigen-specific CD8+ T cell responses, in mice. TLR7-NP adjuvanted influenza subunit vaccine successfully protected mice from heterologous viral challenge. TLR7-NP also enhanced the antibody response to a SARS-CoV-2 subunit vaccine against multiple variants and revealed the mobilization of an antiviral response. We further demonstrate enhanced antigen-specific responses in human tonsil organoids with this novel adjuvant.

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Mechanism of activation of porcine dendritic cells by an alpha-D-glucan nanoparticle adjuvant and nanoparticle/poly(I:C) combination adjuvant.

Project description:RNA sequencing was performed to identify immune-related genes that were differentially expressed in porcine monocyte-derived dendritic cells following stimulation with a novel phytoglycogen-based nanoparticle (Nano-11) and the TLR3 agonist poly(I:C).

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Expression data of muscle and draining lymph node after intramuscular ISCOM-Matrix vaccine adjuvant treatment

2012-04-01 | GSE36306 | GEO

A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates

Project description:After clean drinking water, vaccination is the most impactful global health intervention. However, development of new vaccines against difficult-to-target diseases is hampered by the lack of diverse adjuvants for human use. Of particular interest, none of the currently available adjuvants induce Th17 cells. Here, we develop and test an improved liposomal adjuvant, termed CAF®10b, that incorporates a TLR-9 agonist. In a head-to-head study in non-human primates (NHPs), immunization with antigen adjuvanted with CAF®10b induced significantly increased antibody and cellular immune responses compared to previous CAF® adjuvants, already in clinical trials. This was not seen in the mouse model, demonstrating that adjuvant effects can be highly species specific. Importantly, intramuscular immunization of NHPs with CAF®10b induced robust Th17 responses that were observed in circulation half a year after vaccination. Furthermore, subsequent instillation of unadjuvanted antigen into the skin and lungs of these memory animals led to significant recall responses including transient local lung inflammation observed by Positron Emission Tomography-Computed Tomography (PET-CT), elevated antibody titers, and expanded systemic and local Th1 and Th17 responses, including >20% antigen-specific T cells in the bronchoalveolar lavage. Overall, CAF®10b demonstrated an adjuvant able to drive true memory antibody, Th1 and Th17 vaccine-responses across rodent and primate species, supporting its translational potential.

2024-07-24 | GSE241235 | GEO

Primates

Project description:Primates

| PRJNA551411 | ENA

Expression data of muscle and draining lymph node after intramuscular ISCOM-Matrix vaccine adjuvant treatment

Project description:ISCOM vaccines induce a balanced Th1/Th2 response and cytotoxic T lymphocytes. The adjuvant component, ISCOM-Matrix, consists of purified saponin fractions, cholesterol and phospholipids. The mode of action for the ISCOM-Matrix is known to some extent but still we lack knowledge of important segments in initiation of the immune response. The study was performed to analyze the early transcriptional responses to the ISCOM-Matrix alone, without the use of co-administered antigen. Matrix M (AbISCOÂ® 100) was given as intramuscular injection and after 24 hours the pigs was sacrificed for gene expression analysis, performed for the injection site and the draining lymph node. Results revealed 594 and 362 genes to be differentially expressed (FC > 2; q < 0.05) at the injection site and in the lymph node, respectively. This show that the ISCOM-Matrix, without any antigen added, has a clear immunomodulatory effect at the site of administration as well as in the draining lymph node. Six pigs, castrated males, 11 weeks old was used for the experiment. They were sorted two weeks prior the treatment and kept separate throughout the experiment. 3 pigs were intramuscularly (biceps femoris) injected with ISCOM-Matrix (AbISCOÂ® 100) suspended in 1 ml sterile saline. 3 control animals were similarly injected with saline only. The pigs were sacrificed after 24 hours and muscle tissue from injection site and draining (internal iliac) lymph nodes were collected and transferred to RNAlater for RNA isolation.

2012-03-31 | E-GEOD-36306 | biostudies-arrayexpress

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