Abstract:The development of a vaccine that can induce high titers of functional antibodies against HIV-1 remains a high priority. We have developed an adjuvant based on an oil-in-water emulsion that incorporates Toll-like receptor (TLR) ligands to test whether triggering multiple pathogen-associated molecular pattern receptors could enhance immunogenicity. Compared to single TLR agonists or other pairwise combinations, TLR7/8 and TLR9 agonists combined were able to elicit the highest titers of binding, neutralizing, an… Show more
“…Covalent heterodimers of TLR2 and TLR9 agonists have been shown to elicit enhanced NF-κB expression in DCs relative to stimulation with physical mixtures of these ligands in vitro, and this response may be linked to enforced spatial colocalization of TLRs and their associated adaptor molecules (76). The use of particulate or oil-in-water formulations also facilitates combination delivery of danger signals in mouse and NHP models (73,77). PLGA nanoparticles encapsulating TLR4 and TLR7 agonists were found to synergistically promote strong antibody titers and increase the number of GCs following vaccination in mice, while avoiding the toxicity of the free adjuvant compounds (48).…”
Section: Codelivery Of Antigen and Danger Signalsmentioning
confidence: 99%
“…For example, a cancer vaccine based on irradiated flagellin-and ovalbuminexpressing tumor cells was shown to elicit potent T cell responses in mice, dependent on both TLR5 and the Nod-like receptors NLRC4 and NAIP5 (72). In NHPs, combinations of TLR7/8 and TLR9 agonists enhanced the induction of binding and neutralizing antibody titers against an HIV envelope immunogen (73). High-throughput screening has begun to be applied to the problem of defining optimal danger signal combinations, and in vitro assays predictive of in vivo vaccine performance should enable more facile exploration of the vast parameter space of possible adjuvant combinations (74).…”
Section: Codelivery Of Antigen and Danger Signalsmentioning
“…Covalent heterodimers of TLR2 and TLR9 agonists have been shown to elicit enhanced NF-κB expression in DCs relative to stimulation with physical mixtures of these ligands in vitro, and this response may be linked to enforced spatial colocalization of TLRs and their associated adaptor molecules (76). The use of particulate or oil-in-water formulations also facilitates combination delivery of danger signals in mouse and NHP models (73,77). PLGA nanoparticles encapsulating TLR4 and TLR7 agonists were found to synergistically promote strong antibody titers and increase the number of GCs following vaccination in mice, while avoiding the toxicity of the free adjuvant compounds (48).…”
Section: Codelivery Of Antigen and Danger Signalsmentioning
confidence: 99%
“…For example, a cancer vaccine based on irradiated flagellin-and ovalbuminexpressing tumor cells was shown to elicit potent T cell responses in mice, dependent on both TLR5 and the Nod-like receptors NLRC4 and NAIP5 (72). In NHPs, combinations of TLR7/8 and TLR9 agonists enhanced the induction of binding and neutralizing antibody titers against an HIV envelope immunogen (73). High-throughput screening has begun to be applied to the problem of defining optimal danger signal combinations, and in vitro assays predictive of in vivo vaccine performance should enable more facile exploration of the vast parameter space of possible adjuvant combinations (74).…”
Section: Codelivery Of Antigen and Danger Signalsmentioning
“…The intramuscular (i.m.) component of the combined boost consisted of 100 g HIV Env C.1086 gp120 and 250 l of the adjuvant STR8S-C (squalene-containing STS base adjuvant plus R848 plus oCpGs) (21). i.n.…”
Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia
More than 200,000 new pediatric human immunodeficiency virus (HIV) infections occur annually via mother-to-child transmission (MTCT), nearly half through breastfeeding (1). Antiretroviral (ARV) drugs can dramatically reduce the rate of MTCT, but in areas of high HIV prevalence, acute HIV infection in pregnant and postpartum women as well as poor access and adherence to ARV treatment throughout the breastfeeding period has limited progress in the prevention of breast milk transmission (2). According to UNAIDS in 2014, only 68% of HIV-infected pregnant women in low-and middle-income countries received ARV therapy during pregnancy, and only 61% of those women continued this therapy postpartum (3). Despite the risk of HIV acquisition, breastfeeding is necessary for infant survival in many regions of the world, as breastfed infants have lower rates of diarrheal and respiratory infections (4). It is well established that antibodies are transferred to infants via the placenta and through breast milk consumption (5); thus, maternal immunization could
“…The evidence is both epidemiologic and genetic. The Toll-like receptors (TLR) 7 and 8 genes, encoding for the innate receptors for single-stranded viral RNA and related to the antiviral responses, 71 have been found to be associated with CD. 72 Similarly, the TLR3 and TLR4 genes, which play an important role in the innate immune response triggered by viral infection, are responsible for the development of both T1DM and CD.…”
Abstract:The objective of this study was to perform a review of the present knowledge on the epidemiology and pathogenesis of the association between celiac disease (CD) and type 1 diabetes mellitus (T1DM). Results from this review show that the estimated prevalence rate of CD in T1DM ranges from 4% to 11.5%, which seems higher in children than in adults, while there is no sex predominance in the prevalence of CD in T1DM. On the basis of the previous literature, screening for CD should be considered at diabetes diagnosis in all subjects and again within 2 and 5 years after diagnosis, even in the absence of symptoms. The anti-islet antibodies detection test, instead, is not recommended in CD, just as in the general population, except for CD patients having a relative with T1DM. Both genes and environmental factors seem to play a role in this association. HLADQ2 has been found to be the most frequent allele in the patients with both CD and T1DM, while gluten may be considered the trigger that induces the production of autoantibodies and the development, in genetically predisposed individuals, of both diseases.
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