Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne’s Disease

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of ruminant enteritis, targets intestinal macrophages. During infection, macrophages contribute to mucosal inflammation and development of granulomas in the small intestine which worsens as disease progression occurs. Vitamin D3 is an immunomodulatory steroid hormone with beneficial roles in host-pathogen interactions. Few studies have investigated immunologic roles of 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in cattle, particularly cattle infected with MAP. This study examined the effects of exogenous vitamin D3 on immune responses of monocyte derived macrophages (MDMs) isolated from dairy cattle naturally infected with MAP. MDMs were pre-treated with ± 100 ng/ml 25(OH)D3 or ± 4 ng/ml 1,25(OH)2D3, then incubated 24 hrs with live MAP in the presence of their respective pre-treatment concentrations. Following treatment with either vitamin D3 analog, phagocytosis of MAP by MDMs was significantly greater in clinically infected animals, with a greater amount of live and dead bacteria. Clinical cows had significantly less CD40 surface expression on MDMs compared to subclinical cows and noninfected controls. 1,25(OH)2D3 also significantly increased nitrite production in MAP infected cows. 1,25(OH)2D3 treatment played a key role in upregulating secretion of pro-inflammatory cytokines IL-1β and IL-12 while downregulating IL-10, IL-6, and IFN-γ. 1,25(OH)2D3 also negatively regulated transcripts of CYP24A1, CYP27B1, DEFB7, NOS2, and IL10. Results from this study demonstrate that vitamin D3 compounds, but mainly 1,25(OH)2D3, modulate both pro- and anti-inflammatory immune responses in dairy cattle infected with MAP, impacting the bacterial viability within the macrophage.

Seroconversion rates following 2 doses of measles- mumps- rubella vaccination given at the ages 12 and 18 months: data for possible additional dose at older age

Background Despite high rate of vaccination coverage with 2-doses of measles containing vaccine among Iranian children, outbreaks of measles occurred among different age groups and fully vaccinated subjects. Although the main reason for these outbreaks is unknown, however, vaccine failure was supposed to be an important cause. This study was designed to determine the seroconversion rates to measles- mumps- rubella (MMR) vaccine currently in use among Iranian children. Methods This prospective study was conducted among healthy children older than 12 months who were candidates of scheduled MMR vaccination. Blood samples were obtained from each mother- infant pair just before vaccination, and from infants 4–6 weeks after MMR1 and MMR2 immunization. Collected sera were tested for specific lgG antibodies against MMR agents using ELISA method. The proportion of seroprotected subjects among mother- infant pairs before vaccination as well as the prevalence rates of seroconversion after MMR1 and MMR2 vaccination were calculated. Collected data were analyzed using descriptive statistical methods. Results During 22-months study period, 92 mother- infant pairs were participated. Seroimmunity rates against MMR viruses were 85.8%, 84.7% and 86.9% for mothers, and 3.2%, 2.1% and 1.0% for children, respectively. After MMR1 vaccination from 52 seronegative children, 80.7%, 78.8% and 75% were seroconverted. These rates increased to 94.8%, 89.7% and 94.8% after the MMR2 vaccination. Also, the specific immunity was enhanced among seropositive children. Conclusion Majority of the mothers and few infants were immune to MMR viruses prior to MMR1 vaccination. Immune responses detected after MMR1 injection, and overall seroconversion rates achieved after 2-doses of MMR vaccination were less than expected and inadequate to preserve long-term protection against MMR agents.

Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, one B-box motif, one coiled-coil domain at the N-terminal, as well as one PRY domain and one SPRY domain at the C-terminal. TRIM21 is expressed in many tissues and plays an important role in systemic autoimmunity. However, TRIM21 plays different roles in different virus infections. In this study, we evaluate the relationship between porcine TRIM21 and PCV2 infection as well as host immune responses. We found that PCV2 infection modulated the expression of porcine TRIM21. TRIM21 can enhance interferons and proinflammatory factors and decrease cellular apoptosis in PCV2-infected cells. These results indicate that porcine TRIM21 plays a critical role in enhancing PCV2 infection, which is a promising target for controlling and developing the treatment of PCV2 infection.

Use of a Clostridioides difficile Murine Immunization and Challenge Model to Evaluate Single and Combination Vaccine Adjuvants Consisting of Alum and NKT Cell-Activating Ligands

Adjuvant combinations may enhance or broaden the expression of immune responses to vaccine antigens. Information on whether established Alum type adjuvants can be combined with experimental CD1d ligand adjuvants is currently lacking. In this study, we used a murine Clostridioides difficile immunization and challenge model to evaluate Alum (Alhydrogel™), α-galactosylceramide (α-GC), and one of its analogs 7DW8-5 singly and in combination as vaccine adjuvants. We observed that the Alum/α-GC combination caused modest enhancement of vaccine antigen-specific IgG1 and IgG2b responses, and a broadening to include IgG2c that did not significantly impact overall protection. Similar observations were made using the Alum/7DW8-5 combination. Examination of the impact of adjuvants on NKT cells revealed expansion of invariant NKT (iNKT) cells with modest expansion of their iNKTfh subset and little effect on diverse NKT (dNKT) cells. Side effects of the adjuvants was determined and revealed transient hepatotoxicity when Alum/α-GC was used in combination but not singly. In summary these results showed that the Alum/α-GC or the Alum/7DW8-5 combination could exert distinct effects on the NKT cell compartment and on isotype switch to produce Th1-driven IgG subclasses in addition to Alum/Th2-driven subclasses. While Alum alone was efficacious in stimulating IgG-mediated protection, and α-GC offered no apparent additional benefit in the C. difficile challenge model, the work herein reveals immune response features that could be optimized and harnessed in other vaccine contexts.

Host Factors Impacting the Development and Transmission of Bovine Digital Dermatitis

This review provides insight on potential host-specific factors that increase individual susceptibility to infection and transmission of bovine digital dermatitis. Digital dermatitis is increasing in prevalence within herds worldwide and yields economic losses for producers and welfare issues for animals. A total of 34 relevant studies were reviewed based on the inclusion criteria. A decrease in susceptibility to disease was found in animals with specific genomic and hoof characteristics, thus citing the importance of sire selection when designing a breeding program. Animals with superior health status that lacked co-morbidities and mounted immune responses to infection were less likely to develop disease. Primiparous cattle and those in peak production were more likely to develop lesions, as were over-or-under-conditioned Holstein–Friesian breeds. Cattle with superior hoof conformation and gait were poor hosts for bacteria and therefore less likely to develop and spread infection. The lowest risk of transmission of digital dermatitis occurred during the dry period and post peak lactation and cattle with advanced lesions contributed to the persistence of the disease within a herd. It is hoped that this review will help producers design breeding and management programs for their herds, and help veterinarians advise clients on the subject.

Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

Immune imprinting For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immune responses to heterologous variants are influenced by a person’s infection history. Healthcare workers (HCWs) may be exposed to several doses and types of antigens, either by natural infection or by vaccination. Reynolds et al . studied a cohort of UK HCWs followed since March 2020. The immunological profiles of these people depended on how often the subject had encountered antigen and which variant was involved. Vaccine responses after infection were found to be less effective if the infection involved heterologous spike from a variant virus. Unfortunately, the N501Y spike mutation, found in many variants, seems to induce the regulatory T cell transcription factor FOXP3, indicating that the virus could subvert effective T cell function. Changes to antibody binding between variants also means that serology data using the Wuhan Hu-1 S1 receptor-binding domain sequence may not be a reliable measure of protection. —CA