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Our understanding of the deterioration in immune function in old age—immunosenescence—derives principally from studies of modern human populations and laboratory animals. The generality and significance of this process for systems experiencing complex, natural infections and environmental challenges are unknown. Here, we show that late-life declines in an important immune marker of resistance to helminth parasites in wild Soay sheep predict overwinter mortality. We found senescence in circulating antibody levels against a highly prevalent nematode worm, which was associated with reduced adult survival probability, independent of changes in body weight. These findings establish a role for immunosenescence in the ecology and evolution of natural populations.

Background Parasitic infections are prevalent among lambs in the subtropics, adversely affecting immunity, liver health and growth performance. To efficiently combat these issues, herbs as supplements are an effective approach. Objectives The present study aims to evaluate the efficacy of lemongrass powder on growth performance, nutrient digestibility, blood biomarkers, liver enzymes, immune and endo‐parasitic status in lambs (Ovis aries). Methods Ten lambs (body weight [BW]: 16.67 ± 3.82 kg) were randomly assigned to two diets (5 lambs/diet) in a crossover design, consisting of two 35‐days feeding periods separated by a 14‐days washout interval. The basal diet had 14.90% crude protein and 10.57 mega joules of metabolizable energy/kg of dry matter (DM) and was considered the control diet (CL‐diet), and the lemongrass diet (LS‐diet) consisted of the basal diet + 0.50 g of lemongrass powder/kg of metabolic BW of a lamb. Feed, faeces and blood samples were collected during each feeding period. Results Lambs receiving the LS‐diet presented a better propensity of DM consumption (p = 0.07), greater average daily gain (p = 0.06), while showing a better feed conversion ratio (p = 0.05) and higher growth velocity (p = 0.02) compared to the CL‐diet. In addition, lambs given the LS‐diet improved nutrient digestibility, serum high‐density lipoprotein cholesterol and albumin, while reducing serum triglycerides, low‐density lipoprotein cholesterol and globulin compared to the CL‐diet (p < 0.05). However, feeding the LS‐diet to lambs had no impact on serum total protein, immunoglobulin (Ig)‐M, alanine aminotransferase and gamma‐glutamyltransferase, while substantially improving serum IgG and reducing aspartate aminotransferase and alkaline phosphatase, thereby improving immunity and liver health. Lambs given the LS‐diet effectively suppressed stomach worms, Paramphistomum spp. and Eimeria spp. (p < 0.05). Conclusions Lemongrass powder as a supplement with a basal diet had a positive impact on growth velocity, digestibility, serum cholesterol levels, liver health, immunity and endo‐parasitic status in lambs. Dietary supplementation of lemongrass powder (0.50 g per kg metabolic body weight) with a basal diet significantly enhanced lamb daily gain, growth velocity, feed efficiency and nutrient digestibility. It increased serum high‐density lipoprotein cholesterol (HDL‐C), albumin and IgG concentrations, while reducing aspartate aminotransferase (AST), alkaline phosphatase (ALP), total cholesterol, low‐density lipoprotein cholesterol (LDL‐C) and endo‐parasitic load, highlighting its potential as a natural supplement in tropical lamb production.

Gastrointestinal nematodes (GINs) are responsible for high morbidity and mortality rates in the sheep industry. This study aimed to identify functional INDELs responsible for splice sites using RNA-Sequencing from the liver tissue of sheep with different innate immune responses after being naturally exposed to GIN infection. Two GIN-naïve groups of lambs with divergent cortisol levels (high stress responders - HSR and medium stress responders - MSR) were naturally exposed to GIN during grazing. The animals were euthanized, and six HSR and six MSR, in addition to four immunological control animals (GIN-unexposed), were selected for RNA sequencing from liver tissue. Variant INDELs were identified, and variant consequences analysis was performed to identify INDELs responsible for splice site (SS). A total of 34,168 and 39,380 INDELs were identified for the HSR and MSR, respectively. From those, 1,614 and 2,980 INDELs were responsible for possible SS. The location of the INDELs yielded a list of 514 and 855 genes for HSR and MSR, respectively. Among these genes, the STAT6 and CFI genes were identified. The CFI gene was previously identified as differentially expressed in resistant lines of sheep exposed to GIN, and the STAT6 gene appears to play an important role in the immune response to helminths. The Terminal pathway of complement was enriched (FDR > 0.05) and could be playing a role in building an innate immune response to GIN infection. This study identified novel INDELS responsible for possible SS in genes that could be modulating the immune response to GIN in sheep. Furthermore, enriched immune-related pathways were discovered, suggesting previously uncharacterized components in the inflammatory response to GIN in sheep.

•An attenuated Brucella melitensis vaccine M5-90 has been mostly used for animals in China.•Immune response to BP26 and OMP31 of the vaccine was evaluated in sheep.•Specific antibody and IFN-γ response were detected at low levels in vaccinated sheep.•Protective efficacy of the vaccine was overall weak and shortlived.•These data are helpful to design a safer and more effective B. melitensis vaccine. In recent years, the number of cases of human brucellosis has been increasing by approximately 10% per year in China. Most cases were caused by Brucella melitensis through contacts with infected sheep, goats or their products. An attenuated B. melitensis vaccine M5-90 is currently used to vaccinate both animals in China. This vaccine has not been investigated for critical parameters such as immune response and its association with protective efficacy. In this study, humoral and cellular immune response to the periplasmic protein BP26 and the outer membrane protein OMP31 were evaluated in M5-90 vaccinated Chinese merino and Kazak sheep. Antibodies to BP26 or OMP31 were detected at low levels, and specific IFN-γ response was quantified. Strongly reactive peptides derived from BP26 and OMP31 identified five T-cell epitopes (BP26-6, -8, -11, -12 and OMP31-23) common to both sheep species, five species-specific epitopes (BP26-10, -18, -21 and -22 and OMP31-12) and four animal-specific epitopes (BP26-15, -23, OMP31-6 and -21), which stimulated specific IFN-γ response in vaccinated sheep. Among those T-cell epitopes, reactivity to BP26-18 and -21 epitopes was significantly associated with MHC-I B allele (P=0.024). However, a specific T-cell response induced by the M5-90 vaccine was relatively week and did not sustain long enough, which might be suppressed by rapid activation of T-regulatory (Treg) cells following vaccination. These findings provide an insight in designing a safer and more effective vaccine for use in animals and in humans.

A functional immune system is important for survival in natural environments, where individuals are frequently exposed to parasites. Yet strong immune responses may have fitness costs if they deplete limited energetic resources or cause autoimmune disease. We have found associations between fitness and heritable self-reactive antibody responsiveness in a wild population of Soay sheep. The occurrence of self-reactive antibodies correlated with overall antibody responsiveness and was associated with reduced reproduction in adults of both sexes. However, in females, the presence of self-reactive antibodies was positively associated with adult survival during harsh winters. Our results highlight the complex effects of natural selection on immune responsiveness and suggest that fitness trade-offs may maintain immunoheterogeneity, including genetic variation in autoimmune susceptibility.

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suitable for use in livestock or humans outside endemic areas. Here we report the evaluation of the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins. In a previous study, the vaccine elicited strong virus neutralizing antibody responses in sheep and was DIVA ( d ifferentiating naturally i nfected from v accinated a nimals) compatible. In the current efficacy study, a group of sheep ( n  = 5) was vaccinated subcutaneously with the glycoprotein-based subunit vaccine candidate and then subjected to heterologous challenge with the virulent Kenya-128B-15 RVFV strain. The vaccine elicited high virus neutralizing antibody titers and conferred complete protection in all vaccinated sheep, as evidenced by prevention of viremia, fever and absence of RVFV-associated histopathological lesions. We conclude that the subunit vaccine platform represents a promising strategy for the prevention and control of RVFV infections in susceptible hosts.

Yeast culture is widely used in ruminants to improve gut health, immunity, and productivity; however, its impact on meat quality remains unclear. This study aimed to investigate the effects of yeast culture supplementation in the basic diet on meat quality of Small-tail Han sheep. A total of 40 Small-tail Han sheep (17.5 ± 1.2 kg) were randomly assigned to two treatment groups, with 20 sheep in each group. The sheep were fed either a basic diet (CON) or the basic diet supplemented with 1% yeast culture (YSD) for 90 days. At the end of the trial, the Longissimus dorsi muscle (LOD) of the sheep was collected for meat quality evaluation, as well as transcriptome and metabolome analyses. Meat quality data were analyzed using t-tests, while transcriptome and metabolome data were analyzed using bioinformatics tools. The results showed that YSD supplementation significantly reduced carcass fat content (p < 0.05) and increased the pH values (p < 0.05) of LOD compared to the CON group. Multi-omics analysis revealed significant changes in the levels of 349 transcripts and 149 metabolites (p < 0.05) in the YSD group relative to the CON group. These changes were primarily associated with immune response pathways and purine metabolism. Further integrated transcriptomics and metabolomics analysis identified significant alterations in the expression of adenylate kinase 4 (AK4) and ribonucleotide reductase M2 (RRM2), which influenced purine metabolites, such as ADP, GMP, 3′-AMP, 3′-GMP, dGDP, adenine, guanosine, and guanine. These metabolites were markedly upregulated in the LOD of the sheep supplemented with yeast culture. In conclusion, yeast culture supplementation improved the meat quality of Small-tail Han sheep, potentially through the enhancement of immune response and purine metabolism. These findings offer valuable insights into the molecular mechanisms underlying the effects of yeast culture on animal health and meat quality.

Chlamydia abortus is one of the most commonly diagnosed causes of infectious abortion in small ruminants worldwide. Control of the disease (Enzootic Abortion of Ewes or EAE) is achieved using the commercial live, attenuated C . abortus 1B vaccine strain, which can be distinguished from virulent wild-type (wt) strains by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Published studies applying this typing method and whole-genome sequence analyses to cases of EAE in vaccinated and non-vaccinated animals have provided strong evidence that the 1B strain is not attenuated and can infect the placenta causing disease in some ewes. Therefore, the objective of this study was to characterise the lesions found in the placentas of ewes vaccinated with the 1B strain and to compare these to those resulting from a wt infection. A C . abortus -free flock of multiparous adult ewes was vaccinated twice, over three breeding seasons, each before mating, with the commercial C . abortus 1B vaccine strain (Cevac® Chlamydia, Ceva Animal Health Ltd.). In the second lambing season following vaccination, placentas (n = 117) were collected at parturition and analysed by C . abortus -specific real-time quantitative PCR (qPCR). Two placentas, from a single ewe, which gave birth to live twin lambs, were found to be positive by qPCR and viable organisms were recovered and identified as vaccine type (vt) by PCR-RFLP, with no evidence of any wt strain being present. All cotyledons from the vt-infected placentas were analysed by histopathology and immunohistochemistry and compared to those from wt-infected placentas. Both vt-infected placentas showed lesions typical of those found in a wt infection in terms of their severity, distribution, and associated intensity of antigen labelling. These results conclusively demonstrate that the 1B strain can infect the placenta, producing typical EAE placental lesions that are indistinguishable from those found in wt infected animals.

•A recombinant sub-unit vaccine protected sheep against Teladorsagia circumcincta.•Vaccine consists of a cocktail of immunomodulatory and immunodominant antigens.•Vaccination reduced fecal egg counts by 58–70% and adult worm burdens by 56–75%.•Best reported protection using nematode recombinant vaccine in the definitive host. Infection of humans and livestock with parasitic nematodes can have devastating effects on health and production, affecting food security in both developed and developing regions. Despite decades of research, the development of recombinant sub-unit vaccines against these pathogens has been largely unsuccessful. We have developed a strategy to identify protective antigens from Teladorsagia circumcincta, the major pathogen causing parasitic gastroenteritis in small ruminants in temperate regions, by studying IgA responses directed at proteins specific to post-infective larvae. Antigens were also selected on the basis of their potential immunomodulatory role at the host/parasite interface. Recombinant versions of eight molecules identified by immunoproteomics, homology with vaccine candidates in other nematodes and/or with potential immunoregulatory activities, were therefore administered to sheep in a single vaccine formulation. The vaccine was administered three times with Quil A adjuvant and the animals subsequently subjected to a repeated challenge infection designed to mimic field conditions. Levels of protection in the vaccinates were compared to those obtained in sheep administered with Quil A alone. The trial was performed on two occasions. In both trials, vaccinates had significantly lower mean fecal worm egg counts (FWECs) over the sampling period, with a mean reduction in egg output of 70% (Trial 1) and 58% (Trial 2). During the period of peak worm egg shedding, vaccinates shed 92% and 73% fewer eggs than did controls in Trials 1 and 2, respectively. At post mortem, vaccinates had 75% (Trial 1) and 56% (Trial 2) lower adult nematode burdens than the controls. These levels of protection are the highest observed in any system using a nematode recombinant sub-unit vaccine in the definitive ruminant host and indicate that control of parasitic helminths via vaccination with recombinant subunit vaccine cocktails is indeed an alternative option in the face of multi-drug resistance.

The Morbillivirus peste des petits ruminants virus (PPRV) is the causal agent of a highly contagious disease that mostly affects sheep and goats and produces considerable losses in developing countries. Current PPRV control strategies rely on live-attenuated vaccines, which are not ideal, as they cannot differentiate infected from vaccinated animals (DIVA). Recombinant vector-based vaccines expressing viral subunits can provide an alternative to conventional vaccines, as they can be easily paired with DIVA diagnostic tools. In the present work, we used the bovine herpesvirus-4-based vector (BoHV-4-A) to deliver PPRV hemagglutinin H antigen (BoHV-4-A-PPRV-H-ΔTK). Vaccination with BoHV-4-A-PPRV-H-ΔTK protected sheep from virulent PPRV challenge and prevented virus shedding. Protection correlated with anti-PPRV IgGs, neutralizing antibodies and IFN-γ-producing cells induced by the vaccine. Detection of antibodies exclusively against H-PPRV in animal sera and not against other PPRV viral proteins such as F or N could serve as a DIVA diagnostic test when using BoHV-4-A-PPRV-H-ΔTK as vaccine. Our data indicate that BoHV-4-A-PPRV-H-ΔTK could be a promising new approach for PPRV eradication programs.