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GENE EXPRESSION OF AN ANTI-INFLAMMATORY PENTAPEPTIDE ON CIA MURINE DEVELOPMENT

ABSTRACT: Monocyte Locomotion Inhibitory Factor (MLIF), an amoebic peptide, has an anti-inflammatory role, delaying the arrival of mononuclear cells to inflammatory sites, down regulating adhesin molecules and chemokines. We used microarrays to detail the global gene expression underlying anti-inflammatory effect of MILF in an inflammatory model. Collagen type II (CII) emulsified on complet Freund adjuvant, was injected on the tail of the base of DBA1J mice, 8 weeks older, and booster with CII emulsified in incomple Freund adjuvant three weeks later. MLIF was administrated intranasally weekly since one week before induction. Keywords: comparison effect

ORGANISM(S): Mus musculus

PROVIDER: GSE14721 | GEO | 2009/02/07

SECONDARY ACCESSION(S): PRJNA112179

REPOSITORIES: GEO

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Project description:Methods: During the last trimester of the gestation, 12 heifers were immunized using intramuscular injection with heat-killed E. coli P4 emulsified in Montanide ISA 61VG® oil adjuvant (SEPPIC), as recommended by the manufacturer. Two months later, half of the heifers (IM group, n=6) got a second injection as a booster. Others received 50 µg of protein concentrate prepared from E. coli P4 supernate in two quarters (IMM group, n=6). Cows of the control group (CONT, n=6) were injected intramuscularly with adjuvant only at the same dates. Cows were then challenged on average at 49 days in milk in one healthy quarter by infusion of a E. coli P4 bacterial suspension (10e3 bacteria). Blood was collected before experiment, and seven days after the first and the second injection (immunization phase), and then at 0, 12 and 40 hours after infection (challenge phase). Results : Whole blood transcriptome through RNA-seq identifies the main biological functions altered during an E. coli mastitis. Systemic and mammary routes of E. coli immunization elicit different gene expression profiles that correlated with the levels of protection Conclusions: Intramuscular immunization is correlated with a high systemic Th1 response that is not as protective as the local route of immunization. During the last trimester of the gestation, 12 heifers were immunized using intramuscular injection with heat-killed E. coli P4 emulsified in Montanide ISA 61VG® oil adjuvant (SEPPIC), as recommended by the manufacturer. Two months later, half of the heifers (IM group, n=6) got a second injection as a booster. Others received 50 µg of protein concentrate prepared from E. coli P4 supernate in two quarters (IMM group, n=6). Cows of the control group (CONT, n=6) were injected intramuscularly with adjuvant only at the same dates. Cows were then challenged on average at 49 days in milk in one healthy quarter by infusion of a E. coli P4 bacterial suspension (10e3 bacteria). Blood was collected before experiment, and seven days after the first and the second injection (immunization phase), and then at 0, 12 and 40 hours after infection (challenge phase).

Project description:Authorization of the Matrix-M-adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization (WHO) for malaria prevention in children is a milestone in the fight against malaria. Yet, to meet the unprecedented demand for malarial vaccines, there is a pressing need for additional adjuvants that induce robust and durable vaccine-induced immunity. Here, we performed a comparative assessment of three clinically relevant adjuvants (an alum formulation of the TLR7/8 agonist 3M-052 (3M-052+Alum), the TLR4 agonist GLA-LSQ (GLA in liposome QS-21 formulation), and Matrix-M, the currently approved adjuvant for R21) for their capacity to induce durable immune responses to the R21 malaria vaccine in non-human primates. Immunization of macaques with R21 adjuvanted with 3M-052+Alum on a 0, 8, and 24-week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/Matrix-M vaccine and persisted up to 72 weeks with a half-life of 337 (264 – 459) days. A booster dose at 72 weeks induced an antigen-specific recall response, similar to the R21/Matrix-M vaccination. In contrast, R21/GLA-LSQ immunization induced a considerably lower and short-lived response. Consistent with the durability of serum antibody responses, Matrix-M and 3M-052+Alum induced long-lived plasma cells in the bone marrow and other tissues, including the spleen, but GLA-LSQ stimulated only short-lived plasmablasts. Finally, we show distinct innate immune signatures early after vaccination with these adjuvants. While 3M-052+Alum stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, Matrix-M induced an enhanced expression of interferon- and Th2-related signatures more highly after the booster vaccination. Collectively, these findings provide a comparative database on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M-052+Alum as an additional adjuvant for the R21 malaria vaccine.

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GENE EXPRESSION OF AN ANTI-INFLAMMATORY PENTAPEPTIDE ON CIA MURINE DEVELOPMENT

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