A nano particle vector comprised of poly lactic-co-glycolic acid and monophosphoryl lipid A and recombinant <i>Mycobacterium avium</i>
 subsp <i>paratuberculosis</i>
 peptides stimulate a pro-immune profile in bovine macrophages

Souza, Cléverson de; Bannantine, John P.; Brown, Wendy C.; Norton, M. Grant; Davis, William C.; Hwang, Julianne K.; Ziaei, Parissa; Abdellrazeq, Gaber S.; Eren, Meaghan V.; Deringer, James R.; Laws, Elizabeth I; Cardieri, Maria Clara D.

doi:10.1111/jam.13491

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…An early attempt to develop a nano particle-based vaccine incorporating eMMP was not successful (29). Initial studies demonstrated eMMP could be encapsulated in a nano particle lipid carrier and elicit a recall response.…”

Section: Discussionmentioning

confidence: 99%

Vaccination of cattle with a virus-vectored vaccine against a major membrane protein ofMycobacterium a. subsp.paratuberculosiselicits CD8 cytotoxic T cells that kill intracellular bacteria

Mahmoud,

Abdellrazeq,

Franceschi

et al. 2023

Preprint

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Infection of cattle withMycobacterium a. subsp.Paratuberculosis (Map), the causative agent of paratuberculosis, induces an immune response directed toward a 35 kD major membrane protein (MMP) ofMap. CD8 cytotoxic T cells (CTL) are elicited when peripheral blood mononuclear cells from healthy cattle are incubated ex vivo with antigen-presenting cells (APC) primed with bacterial recombinant MMP. Ex vivo development of CTL was MHC-restricted and required the presence of both CD4 and CD8 T cells. The geneMAP2121c,encoding MMP, was modified to express a modified form of MMP (p35NN) in a mammalian cell line, also capable of eliciting an ex vivo CTL response. In the present study, the modified gene for p35NN was placed into a BoHV4 vector to determine the potential use of BoHV-4AΔTK-p35NN as a peptide-based vaccine. Subcutaneous vaccination of healthy cattle with BoHV-4AΔTK-p35NN elicited a CTL recall response, as detected ex vivo. Further studies are warranted to conduct a challenge study to determine if CD8 CTL elicited by vaccination with BoHV-4AΔTK-p35NN prevents the establishment of a persistent infection byMap.

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Section: Discussionmentioning

confidence: 99%

Vaccination of cattle with a virus-vectored vaccine against a major membrane protein ofMycobacterium a. subsp.paratuberculosiselicits CD8 cytotoxic T cells that kill intracellular bacteria

Mahmoud,

Abdellrazeq,

Franceschi

et al. 2023

Preprint

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“…Although MPL lacks undesirable effects of LPS [ 25 ], it can still induce immune cell activation [ 40 , 41 ]. In the current study, minocycline pretreatment was found to suppress acute MPL injection-induced neuroinflammatory responses in the brain and simultaneously abrogate the preventive effect of MPL pre-injection on CSDS-induced anxiety-like behaviors in mice.…”

Section: Discussionmentioning

confidence: 99%

Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice

Xiang

et al. 2022

J Neuroinflammation

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Background Innate immune pre-stimulation can prevent the development of depression-like behaviors in chronically stressed mice; however, whether the same stimulation prevents the development of anxiety-like behaviors in animals remains unclear. We addressed this issue using monophosphoryl lipid A (MPL), a derivative of lipopolysaccharide (LPS) that lacks undesirable properties of LPS but still keeps immune-enhancing activities. Methods The experimental mice were pre-injected intraperitoneally with MPL before stress exposure. Depression was induced through chronic social defeat stress (CSDS). Behavioral tests were conducted to identify anxiety-like behaviors. Real-time polymerase chain reaction (PCR) and biochemical assays were employed to examine the gene and protein expression levels of pro-inflammatory markers. Results A single MPL injection at the dose of 400 and 800 μg/kg 1 day before stress exposure prevented CSDS-induced anxiety-like behaviors, and a single MPL injection (400 μg/kg) five but not 10 days before stress exposure produced similar effect. The preventive effect of MPL on anxiety-like behaviors was also observed in CSDS mice who received a second MPL injection 10 days after the first MPL injection or a 4 × MPL injection 10 days before stress exposure. MPL pre-injection also prevented the production of pro-inflammatory cytokines in the hippocampus and medial prefrontal cortex in CSDS mice, and inhibiting the central immune response by minocycline pretreatment abrogated the preventive effect of MPL on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine productions in the brain. Conclusions Pre-stimulation of the innate immune system by MPL can prevent chronic stress-induced anxiety-like behaviors and neuroinflammatory responses in the brain in mice.

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“…For example, poly-IC (a synthetic analog of double-stranded RNA), which is recognized through TLR3 and the cytosolic receptor MDA5 (melanoma differentiation-associated gene 5), stimulates Th1 cell immunity, including the generation of cytotoxic CD8 T lymphocytes in mice [157]. A low-toxicity derivative of LPS, monophosphoryl lipid A (MPLA), stimulates TLR4 by the TRIF pathway and biases the response towards Th1 immunity in mice and humans [165], and possibly in cattle [166]. The action of MPLA, which is used in the mastitis vaccine UBAC ® (Hipra S.A.), deserves to be delineated in detail in the bovine species.…”

Section: Improve Knowledge Of Adjuvants For Ruminants To Guide the Im...mentioning

confidence: 99%

Progress towards the Elusive Mastitis Vaccines

et al. 2022

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Mastitis is a major problem in dairy farming. Vaccine prevention of mammary bacterial infections is of particular interest in helping to deal with this issue, all the more so as antibacterial drug inputs in dairy farms must be reduced. Unfortunately, the effectiveness of current vaccines is not satisfactory. In this review, we examine the possible reasons for the current shortcomings of mastitis vaccines. Some reasons stem from the peculiarities of the mammary gland immunobiology, others from the pathogens adapted to the mammary gland niche. Infection does not induce sterilizing protection, and recurrence is common. Efficacious vaccines will have to elicit immune mechanisms different from and more effective than those induced by infection. We propose focusing our research on a few points pertaining to either the current immune knowledge or vaccinology approaches to get out of the current deadlock. A possible solution is to focus on the contribution of cell-mediated immunity to udder protection based on the interactions of T cells with the mammary epithelium. On the vaccinology side, studies on the orientation of the immune response by adjuvants, the route of vaccine administration and the delivery systems are among the keys to success.

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A nano particle vector comprised of poly lactic-co-glycolic acid and monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis peptides stimulate a pro-immune profile in bovine macrophages

Abstract: These results will assist on more in depth studies on PLGA NP delivery systems that may lead to the development of a peptide-based vaccine for cattle.

Cited by 8 publications

References 42 publications

Vaccination of cattle with a virus-vectored vaccine against a major membrane protein ofMycobacterium a. subsp.paratuberculosiselicits CD8 cytotoxic T cells that kill intracellular bacteria

Vaccination of cattle with a virus-vectored vaccine against a major membrane protein ofMycobacterium a. subsp.paratuberculosiselicits CD8 cytotoxic T cells that kill intracellular bacteria

Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice

Progress towards the Elusive Mastitis Vaccines

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