bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-inflammatory and additive-free adjuvant for cutaneous vaccination (113.29)
Authors: Wu Mei , Shah Dilip , Chen Xinyuan , Anderson Richard 
Published: January 2023

Abstract
Skin has been considered an attractive site for vaccine delivery for more than 3000 years, but it is still not commonly used today, because of technical difficulties and a lack of inflammation-free adjuvant. Considerable progress made in generating convenient intradermal (i.d.) injection devices in the past decade raises an urgent need of developing potent vaccine adjuvants that introduce little skin inflammation. Many current vaccine adjuvants cause severe skin inflammation that jeopardizes the integrity of the skin and thus cannot be accepted for cutaneous vaccination. We develop a laser-based vaccine adjuvant (LVA) capable of boosting immune responses without incurring inflammation. LVA was induced by brief (2 min) illumination of a small area of the skin with a safe laser prior to i.d. administration of vaccines at the site of laser illumination. The pre-illumination augmented the hemagglutination inhibition (HAI) titers against seasonal or 2009-pandemic influenza vaccine by 10~20-folds when compared to i.m. immunization. And, while i.d. immunization blocked viral production in the lung by 2-fold over i.m. vaccination, i.d. immunization after laser illumination increased the blockade to 186-fold. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is a risk- and additive-free adjuvant and has distinct advantages over traditional vaccine adjuvants for cutaneous vaccination.
Vaccine Induced Protection of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection in swine (113.3)
Authors: Hemnani Khushboo , Trujillo Jessie , Opriessnig Tanja , Messel Robert , Tobin Gregory , Nara Peter 
Published: January 2023

Abstract
PRRSV is an economically significant Arterivirus of swine health industry. High genetic diversity (up to 20% strain variability), high mutation rate and various immune evasion strategies pose major challenges in the development of an efficacious broadly protective vaccine. One evasion strategy is the presence of non-conserved immunodominant decoy epitopes that divert the immune response towards non-protective, type-specific ones. We hypothesize that masking decoy epitopes with PRRSV specific antibodies, Antibody Immune Masking (AIM), can redirect immune response towards broadly protective neutralizing antibodies. Presented here is the development of an efficacious AIM PRRSV vaccine model capable of inducing sterilizing immunity in some vaccinated pigs and reduction of viremia as well as PRRSV associated pathology in infected pigs. Pigs were vaccinated with AIM or autologous vaccine and later challenged with a homologous/heterologous virus. Results from a trial with 10 pigs per group demonstrated that AIM vaccination was effective in prevention of heterologous infection in 33% of pigs, while others had significant reduction in peak viremia as compared to the autogenous vaccination control pigs (p=0.0034) and unvaccinated controls (p=0.0001); as well as reduction in pulmonary viral loads compared to unvaccinated controls (p=0.0126). Current research is focused on determination and characterization of correlates of immune protection and confirmation of immune refocusing.
Seasonal IM flu-vaccines boost antibody titers to epitopes common to influenza virus strains (113.35)
Authors: Kasten-Jolly Jane , Lawrence David 
Published: January 2023

Abstract
Human serum IgG anti-influenza virus antibodies (Abs) to components of the inactivated, tri-valent 2006/2007, 2007/2008, 2008/2009, and 2010/2011 vaccines were measured by surface plasmon resonance (SPR; BIA3000). Pre- and post (2 wk) 2007/2008 vaccination (N=20 healthy volunteers) serum IgGs were assayed for binding to the 2006/2007, 2007/2008, and 2008/2009 vaccine preparations. Overall, the IgG binding was greatest to the 2006/2007 vaccine components, but binding was also observed against the 2008/2009 vaccine which did not include strains within the 2006/2007 or the 2007/2008 vaccines. Several control individuals who had never received a flu-vaccine showed no binding to any of the vaccines studied. Pre- and post (2 wk) 2010/2011(H1N1, pandemic strain) vaccination Abs were assayed for binding against the 2006/2007, 2007/2008, and the 2010/2011 vaccines. Vaccination with the 2010/2011 vaccine showed a &gt;10 fold boost in IgG binding to both the 2006/2007 and 2010/2011 components and somewhat lower to 2007/2008, compared to the 2-3 fold boosts to the 2006/2007 components observed with the previous vaccinations. The results emphasize that Abs raised against one vaccine preparation can bind strains present in other vaccine preparations. The 2006/2007 vaccine preparation seems to have one or more of these highly antigenic epitopes. Future studies will involve delineation of these sites and investigation into their ability to protect against influenza viral infection.
Long term persistence of IgE anti-hepatitis A virus antibodies in adult serum post vaccination. (113.9)
Authors: Bluth Martin , Kokh Dina , Zhou Weili , Rirash Fadumo , Smith-Norowitz Tamar 
Published: January 2023

Abstract
Rationale: The role of IgE in immunity against Hepatitis A has not been studied. Methods. Serum was obtained from an adult who was vaccinated with Hepatitis A virus (HAV) (Havrix®) in 2005 and again in 2009 and compared with pre vaccination status and natural HAV infection. Serum was assessed for the presence of IgE anti-HAV antibody (modified Immunoblot/ELISA, spectrophotometry) over seven years post vaccination and compared with IgG and IgM virus specific antibodies.. Results. Serum obtained from HAV adult contained IgE anti-virus antibodies which increased over 1.5 years post initial vaccination. In contrast, serum levels of IgE anti-HAV antibodies increased 6 fold two years after 2nd vaccine booster compared with pre-booster levels (1.2OD450 vs 0.21OD450, p&lt;0.05). The rise of IgE anti-HAV levels increased proportionally with time after booster. Interestingly, serum IgE HAV antibody levels seven years post vaccination were comparable to levels of IgE anti-hepatitis antibodies in natural HAV infection (1.2OD450 vs 1.23OD450). Similar patterns were not observed with IgG and IgM anti virus antibodies with respect to consistency and rate of rise. Conclusions. This is the first description of the presence of IgE anti-HAV antibodies, and the first demonstration of its long term persistence serum seven years post vaccination. Understanding the role of IgE anti-virus antibodies may provide insight into vaccine physiology with respect to protection against viral infection.
The CLRX.1/NOD24 pseudogene codes a functional NF-κB regulator, Pyrin-only protein 3 (POP3) (114.10)
Authors: Harton Jonathan , Atianand Maninjay , Porter Kristen 
Published: January 2023

Abstract
Inflammasomes play a crucial role in mediating innate and adaptive immunity against a variety of microbes and danger signals. However, regulatory mechanisms controlling inflammasome effector functions, specifically generation of the bioactive IL-1β in macrophages are not well studied. Pyrin-only proteins (POPs) modulate NF-κB signaling and inflammasome activation, thus restricting the magnitude of innate immune and inflammatory responses in humans. POP1 interferes with IKKα/β activation thus limiting NF-κB activity with no known effect on ASC-dependent inflammasomes. POP2, however, limits the transcriptional activity of NF-κB p65/RelA while also down-modulating the assembly of various ASC-dependent inflammasomes. Here we examine a third human POP, POP3, the product of an NLRP pseudogene with ubiquitous and inducible expression. Like POP1 and POP2, POP3 impairs NF-κB-mediated production of pro-inflammatory cytokines, but fails to inhibit ASC-dependent inflammasomes likely due to the absence of specific acidic residues within its first α helix. Despite high homology to POP2, POP3 is translocated to the nucleus in parallel with NF-kB and inhibits the transcriptional activity of nuclear NF-kB. Collectively, POP3 is a resurrected processed-pseudogene that in addition to other POPs likely represents a further level of control for NF-κB-dependent inflammatory responses
NLRP3 inflammasome dependent loss of mitochondrial and cell membrane integrity in bone marrow derived macrophages (114.3)
Authors: Heid Michelle , Maniar Salony , Watkins Simon , Salter Russell 
Published: January 2023

Abstract
The NLRP3 inflammasome is a multiprotein complex that includes the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which binds with caspase-1 via CARD-CARD interactions and is involved with caspase-1 activation. Pore forming toxins, such as tetanolysin O (TLO), as well as the potassium ionophore nigericin, stimulate the NLRP3 inflammasome. We have observed that NLRP3 knockout macrophages are more resistant to the loss of membrane integrity compared to wild type macrophages exposed to nigericin or TLO, as assessed by a dye uptake assay. Furthermore, this NLRP3 dependent loss of membrane integrity corresponds to the loss of mitochondrial membrane integrity as demonstrated via live cell microscopy. The loss of mitochondrial membrane integrity, but not mitochondrial depolarization was found to be dependent on the presence of NLRP3. Furthermore, the loss of mitochondrial integrity and the loss of cell membrane integrity suggest a potential mechanistic pathway for the effects of NLRP3 inflammasome activation in BMDM. These results further our understanding of how NLRP3 functions in macrophages exposed to stressful stimuli such as bacterial toxins.
Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes (115.16)
Authors: Narayan Kavitha , Sylvia Katelyn , Malhotra Nidhi , Yin Catherine , Martens Gregory , Vallerskog Therese , Kornfeld Hardy , Xiong Na , Cohen Nadia , Brenner Michael , Berg Leslie , Kang Joonsoo , Immunological Genome Project Consortium The 
Published: January 2023

Abstract
Two distinct lineages of T cells, distinguished by expression of either an αβ or γδ T cell receptor (TCR), arise from a common progenitor in the thymus. The type of pathogen and the cytokine milieu directs effector differentiation of αβ T cells in the periphery through the induction of specific transcriptional networks. γδ T cell development is distinct from that of αβ T cells in its ordered rearrangement of TCR genes and the pairing of Vγ and Vδ chains to generate γδ T cell subsets that home to specific tissues. While γδ T cells have primarily been studied as one homogenous population, they can be functionally classified into effector subsets based on the production of signature cytokines, analogous to αβ T helper subsets. Unlike αβ T cells, γδ T cell effector function correlates with genomically encoded TCR chains, but the mechanism of γδ effector specification is unclear. In conjunction with the Immunological Genome Project Consortium, we performed a high resolution transcriptome analysis of all emergent γδ thymocyte subsets segregated based on TCRγ/δ chain usage and maturation state in the thymus. Our data indicate the existence of three separate subtypes of γδ T cells in the thymus. The profiles of the emergent immature γδ T cell subsets are already embedded with unique gene programs directing subset-specific effector function, indicating that γδ T cell effector function is molecularly programmed in the thymus prior to, or concurrent with, TCR expression.
Metabolic profiling of T-cell differentiation and tolerance (115.5)
Authors: Kissick Haydn , Finke Jorge , Dunn Laura , Asara John , Sanda Martin , Arredouani M.Simo 
Published: January 2023

Abstract
Metabolic pathways that drive T cell differentiation, activation and tolerance remain poorly understood. Here we used mass spectrometry to partially describe the metabolic profile of CD4 and CD8 T cells that underwent in vitro activation and differentiation in the presence or absence of prostate cancer conditioned media. T cell subsets were purified from mouse spleen or human PBMC, activated in vitro in the presence of various combinations of cytokines or prostate cancer cell line conditioned media. Metabolites were extracted using methanol, injected and analyzed using a 5500 QTRAP triple quadruple mass spectrometer coupled to a Prominence UFLC HPLC system via selected reaction monitoring (SRM) of a total of 255 endogenous water soluble metabolites for steady-state analyses of samples. Our data show that TCR/CD28-mediated activation imposes a distinct metabolic profile on mouse T cells. This profile is distinct for each cell lineage when activated cells are differentiated into either Th1, Th2, Th9, Th17 or regulatory T cell phenotypes. Likewise, metabolic profiles of activated CD4 and CD8 T cells from both mouse and human are significantly affected by the presence of prostate cancer cell line conditioned media, with major changes in the urea cycle, ammonia recycling, and protein and nucleotide biosynthesis . Together, our findings provide a basis for further development of drugs that could be used to manipulate T cells for a better outcome of prostate cancer vaccines.
microRNA miR-155 regulates NKT cell development and function by targeting ITK (115.6)
Authors: Zhou Li , Li Kai , Zheng Quanhui , Seo Kook-Heon , He Hong-Zhi , Mi Qing-Sheng 
Published: January 2023

Abstract
Invariant Natural Killer T (iNKT) cells are potent regulators of diverse immune responses. Our previous study indicated that lack of miRNAs following the deletion of Dicer, a miRNAs-processing enzyme, affect iNKT cell development and function. However, the roles of specific miRNA in iNKT cell development and function has not been reported. To identify which miRNAs are involved in NKT cell development, we first performed a genome-wide miRNA expression profiling during NKT cell development and found that miR-155 was highly expressed in early iNKT cell development, followed by a sharp decrease in late developmental stage in thymus. To test the role of miR-155 in iNKT cells, two miR155 mutant mouse models had been used. With a conventional miR-155 deficient mouse model, we did not find remarkable defects of iNKT cell development and function. However, overexpression of miR-155 in bone marrow or thymus results in iNKT cell developmental defect in the thymus without dramatic effects on other immune cells. Furthermore, miR-155 overexpressed iNKT cells display profound defects in their cytokine production. Bone marrow from miR-155 overexpressed mice poorly reconstituted iNKT cells, suggesting a cell intrinsic effect. Finally, we have identified Itk (Inducible T cell Kinase) as a direct target of miR-155 in the regulation of iNKT cell development and function. Together, our data suggest that dynamic regulation of miR-155 expression is required for iNKT cell development and function.
Requirement of miR155 for NK cell and CD8+ T cell responses against viral infection (115.7)
Authors: Sun Joseph , Zawislak Carolyn , Loeb Gabriel , Beaulieu Aimee , Bezman Natalie , Lanier Lewis 
Published: January 2023

Abstract
Natural killer (NK) cells and CD8+ T cells function similarly in the recognition and destruction of host cells infected with pathogens. Although microRNAs (miRs) are critical for NK and T cell development and function, the role of specific miRs remain to be investigated. We discovered that miR155 is induced in activated NK cells during mouse cytomegalovirus (MCMV) infection. Using mice containing a targeted deletion of miR155, we determined that miR155 is indispensible for MCMV-specific NK cell expansion and generation of long-lived NK cells. Although miR155-deficient NK cells do not have any defects in basal NK cell homeostasis or function, they exhibit severely impaired effector and memory cell numbers in both lymphoid and non-lymphoid tissues following viral infection. Furthermore, miR155-deficient CD8+ T cells are similarly compromised in their ability to undergo clonal expansion and survive following MCMV infection, together resulting in substantially diminished memory cell numbers. Thus, miR155 is essential for the generation of protective effector and memory NK and CD8+ T cells during viral infection.
A small peptide binds to pathogenic effector cells to prevent/reverse hyperglycemia in T1D (116.1)
Authors: Wagner David , Olmstead Michael 
Published: January 2023

Abstract
CD40 plays a prominent role in autoimmunity. We described its expression on CD4 cells termed CD4CD40 cells. Diabetogenic T cell clones are CD40+ while non-diabetogenic clones are CD40-. CD4CD40 cells expand in number in NOD mice developing progressive insulitis and hyperglycemia and are necessary for adoptive transfer of T1D to NOD.scid recipients. CD4CD40 cells are found in human subjects, significantly (p&lt; 10-7) increased in T1D, including new onset and long term (&gt; 40 yrs) T1D subjects. CD4CD40 cells are expanded regardless of HLA haplotype but occur at normal levels in non-diabetics even those carrying predictive HLAs. CD4CD40 cells are significantly increased in diagnosed pre-diabetic subjects suggesting a biomarker for T1D diagnosis. CD4CD40 cells produce predominantly Th1 cytokines but also produce IL-17 suggesting an intermediary between Th1 and Th17 cells. Blocking CD40 - CD154 with anti-CD154 antibody prevents diabetes and contains CD4CD40 cell expansions. A 15 amino acid peptide derived from the CD154 protein sequence binds directly to CD4CD40 cells and prevents hyperglycemia onset. Furthermore the peptide reverses hyperglycemia in new onset T1D mice. This peptide constricts CD4CD40 cell numbers similarly to anti-CD154 treatment but does not disrupt immune homeostasis. Peptide treated mice have less islet infiltrates and greater insulin production than controls. Peptide treated mice also have increases in FoxP3+ cells, suggesting a tolerogenic mechanism.
Celastrus suppresses the progression of autoimmune arthritis in rats by reducing cellular migration as well as production of pro-inflammatory cytokines and chemokines (116.11)
Authors: Astry Brian , Venkatesha Shivaprasad , Nanjundaiah Siddaraju , Yu Hua , Tong Li , Moudgil Kamal 
Published: January 2023

Abstract
Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease that affects the synovial joints. The target organ pathology in arthritis is primarily a result of inflammation caused by T cells and other leukocytes accumulating within the joints. These leukocytes produce pro-inflammatory cytokines and chemokines. The prolonged use of conventional anti-inflammatory drugs by RA patients is associated with severe adverse effects. Therefore, the use of natural plant products is on the rise. However, the mechanism of action of such products is poorly defined. Using the rat adjuvant arthritis model of RA, we assessed whether Celastrus aculeatus Merril (Celastrus), a traditional Chinese medicine, can limit the disease, and also examined the mechanisms underlying its anti-arthritic activity. We tested the draining lymph node cells and synovial-infiltrating cells (SIC) of Celastrus-treated versus control rats using flow cytometry and assays for cytokines and chemokines. Arthritic Lewis rats treated with Celastrus had reduced inflammation and pathological damage in the joints compared to controls. Further, Celastrus treatment reduced the frequency of Th17 in the pathogenic cellular infiltrate within the joint, limited the Th17 cell differentiation in lymphoid tissues, and decreased the production of pro-inflammatory cytokines and chemokines (IL-17, IL-6, IL-1β, and RANTES) by the SIC. We suggest that Celastrus be further evaluated as a complementary therapy for RA.
Tregitope mechanism of action and applications for tolerance induction. (116.8)
Authors: Cousens Leslie , McClaine Elizabeth , Levitz Lauren , Tassone Ryan , Messitt Timothy , Martin William , De Groot Anne 
Published: January 2023

Abstract
Tregitopes are T cell epitopes naturally located in immunoglobulins that bind to multiple MHC Class II alleles and induce regulatory T cell (Treg) responses. Harnessing tolerogenic effects of Tregitopes provides a novel tool to suppress unwanted immune responses and maintain antigen-specific tolerance, thus changing treatment paradigms in autoimmunity. We have now demonstrated that APCs present Tregitopes to natural (n) Treg, engage feedback mechanisms promoting a tolerogenic APC phenotype, induce Treg expansion, and modulate antigen-specific effector T cell responses. Proportions of APC expressing MHC II, CD80, and CD86 are suppressed, consistent with reported effects of IVIG (Bayry et al. Blood, 2003, 101:758) and of the IgG-derived peptide hCDR1 (Sela et al. Immunology, 2009, 128:395). Moreover, we observed significant increases in proportions of IL-10-producing CD4+CD25+ FoxP3-expressing nTreg in the presence of Tregitopes. These studies are an exciting first step towards understanding the basic mechanism of Tregitope tolerance induction that we propose to be as follows: 1) APC present Tregitopes to nTreg, 2) nTreg are activated to proliferate and produce IL-10, 3) nTreg provide tolerogenic feedback signals to APC, modulating the APC phenotype, and 4) nTreg and tolerogenic APC together suppress antigen-specific T cell responses. These data suggest a role for Tregitopes in the mechanism of action for IVIG, and provide insight critical for future therapeutic applications.
Inflammatory monocyte recruitment is regulated by IL-23 during systemic bacterial infection (117.1)
Authors: Indramohan Mohanalaxmi , Sieve Amy , Break Timothy , Berg Rance 
Published: January 2023

Abstract
Inflammatory monocytes are innate immune cells that produce TNF-α and NO., and are essential for resistance against various pathogens, including Listeria monocytogenes (LM). IL-23 is an important pro-inflammatory cytokine well known for its role in neutrophil recruitment during multiple infectious and autoimmune diseases. We have previously shown that IL-23 is required for host resistance against LM and for neutrophil recruitment to the liver, but not the spleen, during infection. Despite efficient neutrophil recruitment to the spleen, IL-23p19 knockout (KO) mice have an increased bacterial burden in this organ. Interestingly, specific depletion of neutrophils abrogated the differences in bacterial burden in the livers, but not the spleens of C57BL/6 and IL-23p19 KO mice, suggesting that IL-23 may regulate the recruitment/function of another cell type to the spleen. Accordingly, LM-infected IL-23p19 KO mice had fewer monocytes in the spleen, as well as a reduction in monocyte-recruiting chemokines compared to C57BL/6 mice. This lack of efficient monocyte recruitment resulted in decreased production of monocyte-derived TNF-α and NO., leading to increased bacterial burdens in the spleens of LM-infected IL-23p19 KO mice. Collectively, our data reveal a novel mechanism by which IL-23 provides protection against bacterial infection.