FATTY ACID COMPOSITION OF GOAT MILK PRODUCED UNDER WITH DIFFERENT FEEDING REGIMES AND THE IMPACT ON GOAT CHEESE

Ruminants and their great ability to live and produce on a diet rich in fibre have a great potential to contribute to a healthy and sustainable human nutrition (Hofmann 1989). Sadly, only in times of rising energy prices the following question is asked: How much food can we afford to feed to animals? Taking this aspect into account it is necessary to do as much research as possible on the topic of “Feed no Food” in ruminants’ nutrition. The Thuenen-Institute of Organic Farming in Trenthorst, Germany, has started 2009 the project “Feed less Food” with the dairy goats on the organic experimental station in Trenthorst, Holstein, Northern Germany. The main questions where the impact of reduced concentrate feed on animal welfare, milk yield and milk / milk product quality. In 2012, the main focus was laid on lactation performance and quality traits, defined as the occurrence of essential, to humans’ health contributing fatty acids. Goat milk and its products can contribute to a healthy human nutrition. Yet, we know relatively little about feedstuffs, influencing goat milk yield and its composition. “Feed no Food” is one of the major fields of research of the Thuenen-Institute of Organic Farming (TI) in Trenthorst, Germany. In 2012 two feeding groups were formed and dairy goats received either an estimated 10% or 40% of the total feed intake as concentrates (KF 10 and KF 40). Goats of KF 40 showed a significantly higher 240-day performance (P < 0.05) for the following traits: milk kg, fat kg and protein kg. No significant difference between groups was found for fat and protein content. Furthermore, no significant difference occurred in fatty acid pattern of milk. Short and medium chain fatty acids turned out to be significantly increased in cheese from KF 40. Long chain and polyunsaturated fatty acids occurred significantly more in cheese from goats of KF 10, as well as rumenic acid (CLA) and Ω-3 fatty acids. Ratio of Ω-6:Ω-3 proved to be significantly lower in cheese from KF 10. No significant differences between groups were detected for mean live weights

Immunogenicity and Protection After Vaccination With a Modified Vaccinia Virus Ankara-Vectored Yellow Fever Vaccine in the Hamster Model

The highly efficacious live-attenuated 17D yellow fever (YF) vaccine is occasionally associated with rare life-threatening adverse events. Modified vaccinia virus Ankara (MVA), a non-replicating poxvirus, has been used as a vaccine platform to safely deliver various antigens. A MVA-based YF vaccine (MVA-BN-YF) was tested with and without a non-mineral oil adjuvant in a hamster model of lethal YF disease and protective efficacy of this vaccine was compared with the 17D vaccine. The vaccine candidate MVA-BN-YF generated a protective response in hamsters infected with YFV that was comparable to protection by the live 17D vaccine. Similar levels of neutralizing antibody were observed in animals vaccinated with either vaccine alone or vaccine with adjuvant. Significant improvement in survival, weight change, and serum alanine aminotransferase levels were observed in vaccinated hamsters when administered 42 and 14 days prior to challenge with Jimenez YF virus (YFV). Neutralizing antibodies induced by MVA-BN-YF were transferred to naïve hamsters prior to virus challenge. Passive administration of neutralizing antibody 24 h prior to virus infection resulted in significantly improved survival and weight change. A trend toward reduced liver enzyme levels was also observed. MVA-BN-YF, therefore, represents a safe alternative to vaccination with live-attenuated YFV

Evidence That γδ versus αβ T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

Two types of T cells, αβ and γδ, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of αβ lineage T cells requires the surrogate α chain (pTα), which associates with the T cell receptor (TCR) β chain to form the pre-TCR. γδ lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR γ and δ genes. It has been proposed that the quality of signals transmitted by the pre-TCR and γδ TCR are distinct and that these “instructive” signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25+CD44+c-kit+CD3−CD4−CD8− thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into γδ versus αβ lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7Rneg-lo pro-T cells generated a 13-fold higher ratio of αβ lineage to γδ lineage cells than did IL-7R+ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R+ pro-T cells to develop into TCR-γδ T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-γ gene rearrangement/expression in IL-7R+ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals

Risk of malnutrition in patients with systemic sclerosis-associated interstitial lung disease treated with nintedanib

International audienceOBJECTIVE: To assess adverse events in relation to baseline body mass index (BMI) and the risk of malnutrition in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) treated with nintedanib. METHODS: Among patients with SSc-ILD randomized to receive nintedanib or placebo in the SENSCIS trial, we assessed adverse events in subgroups by baseline BMI ≤20 and &gt;20 kg/m(2) , and the risk of malnutrition using a modified version of the Malnutrition Universal Screening Tool (MUST), over 52 weeks. RESULTS: The adverse event profile of nintedanib was similar between subgroups with baseline BMI ≤20 kg/m(2) (n=61) and &gt;20 kg/m(2) (n=515). In these subgroups, respectively, adverse events led to treatment discontinuation in 16.7% and 15.9% of the nintedanib group and 13.5% and 8.0% of the placebo group. Based on the modified MUST, the proportions of patients who had a low risk of malnutrition at baseline and at their last assessment were 74.0% in the nintedanib group and 78.1% in the placebo group, while the proportions who were classified as at low risk at baseline but at high risk by their last assessment were 4.5% in the nintedanib group and 1.0% in the placebo group. CONCLUSION: In the SENSCIS trial, most patients with SSc-ILD remained at low risk of malnutrition over 52 weeks, but the proportion at high risk was higher in patients treated with nintedanib than placebo. Management of disease manifestations and adverse events that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD

Protection against Marburg Virus and Sudan Virus in NHP by an Adenovector-Based Trivalent Vaccine Regimen Is Correlated to Humoral Immune Response Levels

The Marburg virus (MARV) and Sudan virus (SUDV) belong to the filovirus family. The sporadic human outbreaks occur mostly in Africa and are characterized by an aggressive disease course with high mortality. The first case of Marburg virus disease in Guinea in 2021, together with the increased frequency of outbreaks of Ebola virus (EBOV), which is also a filovirus, accelerated the interest in potential prophylactic vaccine solutions against multiple filoviruses. We previously tested a two-dose heterologous vaccine regimen (Ad26.Filo, MVA-BN-Filo) in non-human primates (NHP) and showed a fully protective immune response against both SUDV and MARV in addition to the already-reported protective effect against EBOV. The vaccine-induced glycoprotein (GP)-binding antibody levels appear to be good predictors of the NHP challenge outcome as indicated by the correlation between antibody levels and survival outcome as well as the high discriminatory capacity of the logistic model. Moreover, the elicited GP-specific binding antibody response against EBOV, SUDV, and MARV remains stable for more than 1 year. Overall, the NHP data indicate that the Ad26.Filo, MVA-BN-Filo regimen may be a good candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks

A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates.

The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Marburg virus (MARV). Immune responses against filovirus GP have been associated with protection from disease. The GP antigens were expressed by adenovirus serotypes 26 and 35 (Ad26 and Ad35) and modified Vaccinia virus Ankara (MVA) vectors, all selected for their strong immunogenicity and good safety profile. Using fully lethal NHP intramuscular challenge models, we assessed different vaccination regimens for immunogenicity and protection from filovirus disease. Heterologous multivalent Ad26-Ad35 prime-boost vaccination regimens could give full protection against MARV (range 75%-100% protection) and EBOV (range 50% to 100%) challenge, and partial protection (75%) against SUDV challenge. Heterologous multivalent Ad26-MVA prime-boost immunization gave full protection against EBOV challenge in a small cohort study. The use of such multivalent vaccines did not show overt immune interference in comparison with monovalent vaccines. Multivalent vaccines induced GP-specific antibody responses and cellular IFNγ responses to each GP expressed by the vaccine, and cross-reactivity to TAFV GP was detected in a trivalent vaccine expressing GP from EBOV, SUDV and MARV. In the EBOV challenge studies, higher humoral EBOV GP-specific immune responses (p = 0.0004) were associated with survival from EBOV challenge and less so for cellular immune responses (p = 0.0320). These results demonstrate that it is feasible to generate a multivalent filovirus vaccine that can protect against lethal infection by multiple members of the filovirus family

Correction: A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates.

[This corrects the article DOI: 10.1371/journal.pone.0192312.]