The aim of the present study was to evaluate the associations between milk recording data, body condition score (BCS), housing factors, management factors and lameness in free stall-housed dairy cows in 3 structurally different regions in Germany. These regions substantially vary regarding herd size, breeds, access to pasture, farm management (family run/company owned), and percentage of organic farms. The data used was collected in a large cross-sectional study from 2016 to 2019. A total number of 58,144 cows from 651 farms in 3 regions of Germany (North (N), East (E) and South (S)) was scored for locomotion and body condition. Additionally, data on milk yield, milk composition, breed, age, as well as information on housing and management were retrieved. One mixed-logistic regression model was fitted per region to evaluate the association of the data with the target variable "lame" and to allow for a comprehensive reflection across different kinds of farming types. In all regions, undercondition (BCS lower than recommended for the lactation stage; N: odds ratio (OR) 2.15; CI 1.96 - 2.34, E: OR 2.66; CI 2.45 - 2.88, S OR 2.45; CI 2.01 - 2.98) and mid-lactation stage (102 - 204 d in milk (DIM); N: OR 1.15; CI 1.05 - 1.27, E: OR 1.24; CI 1.17 - 1.32, S: OR 1.38; CI 1.18 - 1.62) were associated with higher odds for lameness, while overcondition (BCS higher than recommended for the lactation stage; N: OR 0.51; CI 0.44 - 0.60, E: OR 0.51; CI 0.48 - 0.54, S: OR 0.65; CI 0.54 - 0.77) and parity of 1 or 2 was associated with lower odds (parity 1: N: OR 0.32; CI 0.29 - 0.35, E: OR 0.19; CI 0.18 - 0.20, S: OR 0.28; CI 0.24 - 0.33 / parity 2: N: OR 0.51; CI 0.47 - 0.46, E: OR 0.41; CI 0.39 - 0.44, S: OR 0.49; CI 0.42 - 0.57), irrespective of the regional production characteristics. Low energy corrected milk yield (ECM) was associated with higher odds for lameness in S and N (N: OR 1.16; CI 1.05 - 1.27, S: OR 1.43; CI 1.22 - 1.69). Further factors such as pasture access for cows (N: OR 0.64; CI 0.50 - 0.82 and S: OR 0.65; CI 0.47 - 0.88), milk protein content (high milk protein content: N: OR 1.34; CI 1.18 - 1.52 and E: OR 1.17; CI 1.08 - 1.28); low milk protein content: N: OR 0.79; CI 0.71 - 0.88, E: OR 0.84; CI 0.79 - 0.90), and breed (lower odds for "other" (other breeds than German Simmental (SIM) and Holstein Frisian (H)) in E (OR 0.47, CI 0.42 - 0.53) and lower odds both for H and "other" in S (H: OR 0.62; CI 0.43 - 0.90, other: OR 0.46; CI 0.34 - 0.62)) were associated with lameness in 2 regions, respectively. The risk of ketosis (ROK; higher odds in N: OR 1.11, CI 1.01 - 1.22) and somatic cell count (SCC; higher odds in E: increased (>39.9 cells x 1,000/ml): OR 1.10; CI 1.03 - 1.17; high (>198.5 cells x 1,000/ml): OR 1.08; CI 1.01 - 1.06) altered the odds for lameness in 1 region, respectively. Cows from organic farms had lower odds for lameness in all 3 regions (N: OR 0.18; CI 0.11 - 0.32, E: OR 0.39; CI 0.28 - 0.56, S: OR 0.45; CI 0.29 - 0.68). As the dairy production systems differed substantially between the different regions, the results of this study can be viewed as representative for a wide variety of loose-housed dairy systems in Europe and North America. The consistent association between low BCS and lameness in all regions aligns with the previous literature. Our study also suggest that risk factors for lameness partly can differ between geographically regions, potentially due to differences in which dairy production system that is predominantly used and that region-specific characteristics should be taken into account in comparable future projects.

Prepartum vaccinations against neonatal calf diarrhea pathogens are administered in late pregnancy to provide passive immunity to calves through protective colostral antibodies. Potential non-specific effects of the vaccine on maternal innate immune responses and disease susceptibility during the sensitive transition period have not been addressed so far. In this retrospective study, data from 73,378 dairy cows on 20 farms in Germany were analyzed, using linear mixed-effects regression, quantile regression, and decision-tree-algorithms, to investigate the effects of prepartum vaccination on mammary health and milk yield by comparing non-vaccinated and vaccinated transition periods. Herd management-related factors were found to be most influential for mammary health and milk yield. Vaccinated cows were not significantly more likely to develop mastitis and did not have significantly different somatic cell counts and milk yields compared to non-vaccinated cows. Healthy primiparous cows with and without vaccination had similar energy-corrected milk yields. The study concludes that prepartum vaccination against calf diarrhea has no significant effects on mammary health and milk yield. Further research is recommended to investigate potential non-specific vaccine effects on other organ systems, infectious diseases, and production metrics of the dairy cow.

Prepartum vaccination of dairy cows against newborn calf diarrhea protects calves during the first weeks of life via the colostrum. Vaccination may also induce non-specific effects (NSEs) beyond antibody production, altering the disease susceptibility and productivity of the vaccinated mother. This retrospective study analyzed herd records and on-site survey data from 73,378 dairy cows on 20 German farms using linear mixed-effects models and random forest algorithms. Management practices and milk yield showed stronger associations with outcomes than vaccination. However, the cows vaccinated with non-live vaccines had increased odds of retained placenta and metritis (OR: 1.5–1.7), as well as endometritis (OR: 3–6), and were 20–24% less likely to conceive than non-vaccinated cows. Among non-live vaccinated cows, those vaccinated 2.5–4 weeks before calving had an 8% higher non-return rate compared to those vaccinated 6–8 weeks prior. Multiparous cows receiving live vaccine components were 1.9 times more likely to conceive, compared to non-live vaccinated multiparous cows. These findings suggest potential NSE of prepartum vaccination on uterine health and fertility. However, this study’s retrospective design limits causal interpretation, and the benefits in calves may outweigh possible adverse effects. Further research should clarify the mechanisms and optimize vaccine timing and composition.

Prepartum vaccination of dairy cows against newborn calf diarrhea protects calves during the first weeks of life via the colostrum. Vaccination may also induce non-specific effects (NSE) beyond antibody production, altering disease susceptibility and productivity of the vaccinated mother. This retrospective study analyzed herd records and on-site survey data from 73,378 dairy cows on 20 German farms using linear mixed-effects models and random forest algorithms. Management practices and milk yield showed stronger associations with outcomes than vaccination. However, cows vaccinated with non-live vaccines had increased odds of retained placenta and metritis (OR: 1.5–1.7), and endometritis (OR: 3–6), and were 20–24% less likely to be successfully inseminated than non-vaccinated cows. Among non-live vaccinated cows, those vaccinated 2.5–4 weeks before calving had an 8% higher non-return rate compared to those vaccinated 6–8 weeks prior. Multiparous cows receiving live vaccine components were 1.9 times more likely to be successfully inseminated, compared to non-live vaccinated multiparous cows. These findings suggest poten-tial NSE of prepartum vaccination on uterine health and fertility. However, the study’s retro-spective design limits causal interpretation, and the benefits in calves may outweigh possible adverse effects. Further research should clarify mechanisms and optimize vaccine timing and composition.

*equal contribution The activation of hepatic stellate cells (HSCs) is a central pathological process in the development of liver fibrosis. Thus, activated HSCs are attractive targets for antifibrotic therapies. We established an adenoviral based gene transfer system for the selective transduction of HSCs by linking a HSC-specific peptide to the virus envelope. The NGFp peptide displays a part of the nerve growth factor (NGF) binding site to p75 neurotrophin receptor (p75NTR), which is in the liver solely expressed on HSCs. Two different methods for the construction of virus particles selectively infecting HSCs were realized. Both the covalent coupling of the peptide to the fiber by polyethylene glycol (PEG) and a non-covalent linked bispecific anti fiber single chain antibody (S11) were used to modify the natural adenovirus (Ad) tropism of the native adenoviral vector (Ad.GFP; including GFP reporter gene). In vitro studies with primary mouse hepatocytes and in vivo infection experiments with Balb/C mice showed an equivalent inhibition of the Ad tropism to coxsackie-adenovirus receptor (CAR) by PEG- as well as S11-linkage to Ads (Ad.GFP). Additionally, NGFp-coupled Ads transduced selectively primary cultured HSCs and HSCs after intravenous infection of mice livers. The latter could be verified by visualizing the colocalization of GFP fluorescence and HSC-associated vitamin A autofluorescence using intravital fluorescence microscopy and subsequent immunohistochemical analysis of the of GFP and p75NTR The use of p75NTR as a target for redirecting adenoviral vectors to HSCs is a new strategy to modulate these cells selectively. The shift of the natural Ad tropism is possible through covalent and non-covalent linking of the NGFp to the virus envelope. This offers new possibilities to introduce therapeutic genes into HSC without any undesirable side effects on hepatocytes or other non-parenchymal liver cells.