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In the 1950s the myxoma virus was released into European rabbit populations in Australia and Europe, decimating populations and resulting in the rapid evolution of resistance. We investigated the genetic basis of resistance by comparing the exomes of rabbits collected before and after the pandemic. We found a strong pattern of parallel evolution, with selection on standing genetic variation favoring the same alleles in Australia, France, and the United Kingdom. Many of these changes occurred in immunity-related genes, supporting a polygenic basis of resistance. We experimentally validated the role of several genes in viral replication and showed that selection acting on an interferon protein has increased the protein’s antiviral effect.

In recent years, the rabbit hemorrhagic disease virus 2(RHDV GI.2) has rapidly spread worldwide due to its broad natural host range, strong pathogenicity, and significant antigenic differences from the traditional RHDV1 (GI.1). The widespread prevalence of both GI.1 and GI.2 RHDV poses a serious threat to the healthy development of the global rabbit industry. Despite this, there is still a notable absence of effective multivalent or broad-spectrum vaccines for controlling RHD(GI.1 and GI.2). In the present study, we developed a broad-spectrum chimeric antigen vaccine using a substitution strategy targeting the surface loop of the main antigen protein VP60 of RHDV. The chimeric VP60 antigen, expressed by a recombinant baculovirus expression system, was successfully assembled into virus-like particles (VLPs). The VLPs exhibited typical natural virus size and morphology under an electron microscope. Immunization with chimeric VLPs effectively protected rabbits from lethal challenged by both virulent strains of RHDV, GI.1 and GI.2, showing an effect comparable to that of a mixture vaccine containing two wild-type VLPs. These findings demonstrate a promising strategy for developing a cost-effective and straightforward preparation process for broad-spectrum vaccine against RHD. •The Loop region of the VP60 protein, found in the rabbit hemorrhagic disease virus and its variant strains, plays a pivotal role in generating protective antibodies.•The sequence substitution in the loop region is prominently exhibited on the surface of the heterotypic VP60 protein, without impeding the formation of chimeric virus-like particle (VLP).•The chimeric virus-like particles have the ability to simultaneously elicit hemagglutination inhibition antibodies against GI.1 and GI.2 VP60 protein, demonstrating effective protection against GI.1 and GI.2 rabbit hemorrhagic disease virus.

► Vaccination against Staphylococcus aureus is achieved with toxoids. ► Toxoids are >107 inactivated and stimulate immunity to S. aureus. ► Superantigen toxoids exhibit adjuvant activity dependent on immune co-stimulatory molecule CD40 binding activity. ► Protective neutralizing antibodies are produced in rabbits to toxic shock syndrome toxin-1. Staphylococcus aureus causes significant illnesses throughout the world, including toxic shock syndrome (TSS), pneumonia, and infective endocarditis. Major contributors to S. aureus illnesses are secreted virulence factors it produces, including superantigens and cytolysins. This study investigates the use of superantigens and cytolysins as staphylococcal vaccine candidates. Importantly, 20% of humans and 50% of rabbits in our TSS model cannot generate antibody responses to native superantigens. We generated three TSST-1 mutants; G31S/S32P, H135A, and Q136A. All rabbits administered these TSST-1 toxoids generated strong antibody responses (titers>10,000) that neutralized native TSST-1 in TSS models, both in vitro and in vivo. These TSST-1 mutants lacked detectable residual toxicity. Additionally, the TSST-1 mutants exhibited intrinsic adjuvant activity, increasing antibody responses to a second staphylococcal antigen (β-toxin). This effect may be due to TSST-1 mutants binding to the immune co-stimulatory molecule CD40. The superantigens TSST-1 and SEC and the cytolysin α-toxin are known to contribute to staphylococcal pneumonia. Immunization of rabbits against these secreted toxins provided complete protection from highly lethal challenge with a USA200 S. aureus strain producing all three exotoxins; USA200 strains are common causes of staphylococcal infections. The same three exotoxins plus the cytolysins β-toxin and γ-toxin contribute to infective endocarditis and sepsis caused by USA200 strains. Immunization against these five exotoxins protected rabbits from infective endocarditis and lethal sepsis. These data suggest that immunization against toxoid proteins of S. aureus exotoxins protects from serious illnesses, and concurrently superantigen toxoid mutants provide endogenous adjuvant activity.

This study evaluated leukocyte and immune parameters in female rabbits and their kits from three genetic lines (R, RF, and RFLP) during their first reproductive cycle. The R line was selected for growth rate over 37 generations, the RF line was derived from elite R animals, and the RFLP was obtained by backcrossing the RF line with a maternal line (LP). In females, the total lymphocyte percentage decreased from the first AI to weaning (−15.8 percentage points; p  < 0.001; MIXED model); granulocytes peaked at weaning (+12.4 percentage points greater than the AI and +4.4 percentage points greater than parturition; p  < 0.01; MIXED model). The CD4 +  /CD8 +  ratio increased 53.4% ( p  < 0.001; MIXED model), and the haptoglobin concentration doubled ( p  < 0.001; MIXED model). RF and RFLP had higher total lymphocyte percentages than R did (+6.4 and +4.6 percentage points; p  < 0.05; MIXED model). R females had lower CD4 +  percentages and CD4 +  /CD8 +  ratios than RLFP females did (−3.4 percentage points and −24.4%; p  < 0.05; MIXED model) but higher monocyte and granulocyte percentages (on average +0.9 and +4.1 percentage points; p  < 0.05; MIXED model). At weaning, R kits had fewer T lymphocytes and CD4 +  T lymphocytes than RF kits did (−8.1 and −6.1 percentage points; p  < 0.05; GLM) and lower CD25 +  and phagocytosis of heterophils than RFLP kits did (−0.8 and −1.2 percentage points; p  < 0.05; GLM). The results suggest that creating a paternal line via elite animals (RFs) and backcrossing it with a robust line could improve immune status and stayability, offering insights into the impacts of rabbit breeding on immune health and reproductive success.

In 2010, rabbit hemorrhagic disease virus (RHDV) GI.2 emerged, and unlike RHDV GI.1, it caused mortality in young rabbits, while existing vaccines were not fully protective. The GI.2-specific monoclonal antibody (mAb) 2D9 has been used as a tool to discriminate between these viruses in diagnostic tests. In this study, we mapped the binding epitope for 2D9 on the GI.2 The VP60 capsid protein demonstrated the neutralizing capacity of this mAb, which was able to prevent GI.2 infections in an experimental challenge. Our results suggest that external loops (1, 4 and 5) in the P2 subdomain of VP60 contribute to the discontinuous neutralizing epitope recognized by mAb 2D9. Moreover, analysis of naturally occurring RHDV GI.2 isolates revealed key residues involved in mAb 2D9 binding that are under selective pressure. The findings described in this work provide valuable information regarding our understanding of virus neutralization and immune escape, which may help in the development of novel antiviral compounds.

In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies. Immunology: Rabbit antibodies show potential for diagnosis and treatment Highly specialized antibodies derived from rabbits could transform our ability to detect and treat diseases such as cancer and HIV. Christoph Rader and co-workers at The Scripps Research Institute in Florida, USA, reviewed the use of rabbit antibodies in research, diagnostics and therapy. Rabbits are commonly used as models in immunology because of their highly sensitive immune system, which generates large numbers of antibodies in response to multiple antigens. Rabbit polyclonal antibodies, antibodies that target different ‘epitopes’ (or sites) on an antigen molecule, are used to prevent and treat transplant rejection. Rader's team highlights the outstanding performance in pre-clinical studies of novel rabbit monoclonal antibodies (mAbs), highly specialised antibodies that target single epitopes. Among many potential applications, rabbit mAbs can detect and destroy cancer cells, and may aid in developing vaccines for diseases like HIV.

Rabbit hemorrhagic disease virus 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly once introduced in a rabbit population. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

Rabbit Haemorrhagic Disease (RHD) is a lethal infection caused by calicivirus that kills 90% of the infected adult rabbits within 3 days. The calicivirus replicates in the liver and causes a fulminant hepatitis. Most studies on the pathology of RHD have been focused on the fulminant liver disease. This may not be the only mechanism in the pathogenesis of RHD: calicivirus infection may also induce leukopenia in the infected adult rabbits. We show now by flow cytometry analysis that the calicivirus induces an early decrease in B and T cells, in both spleen and liver. The depletion of B and T cells was associated with apoptosis labelled by annexin V. These changes occurred in rabbits before they showed enzymatic evidence of liver damage and persisted after liver transaminase values were very high. We conclude that depletion of lymphocytes caused by the calicivirus infection precedes or attends liver damage. The relative contribution of this lymphocyte depletion for the pathogenesis of the fatal calicivirus infection of rabbits remains to be investigated.

The current study aimed to test the effect of Moringa oleifera extract (MOE), vitamin (Vit) C, and sodium bicarbonate (NaHCO₃) on heat stress (HS)-induced alterations in rabbits. Five groups of rabbits were designed as control, HS, HS + MOE, HS + Vit C, and HS + NaHCO₃. HS groups were exposed to high temperatures, while treatments were given in drinking water for 6 weeks. Levels of blood cortisol, leptin, IFN-γ, TNF-α, and IL-10 were assayed using ELISA, while adrenaline was assayed calorimetrically. Expression of HSP70, FOXP3, T cell receptor (TCR) γ, and mRNA was tested using real-time (RT)-PCR, while HSP70 protein expression was tested using western blotting in liver and kidney tissues. Infiltration of regulatory cells (Treg; CD25⁺) and NK (CD56⁺) cells were tested using immunohistochemistry (IHC). The levels of liver enzymes (ALT & AST), urea, and creatinine were assayed calorimetrically, while body weight gain (BWG) and feed conversion ratio (FCR) were calculated. The results showed increased levels of cortisol, adrenaline, leptin, IFN-γ, TNF-α, ALT, AST, urea, and creatinine but decreased IL-10 in the HS group. Increased expression of HSP70 on both mRNA and protein levels was associated with increased NK and γδT cells versus decreased Treg cell infiltration in liver and kidney tissues of the HS group. In the same group, BWG was decreased, while FCR was increased with respect to the control group. All treatments used in this study reversed the effects of HS significantly. In conclusion, MOE, Vit C and NaHCO₃ can be added to rabbit diets for the amelioration of HS-induced symptoms.

Background Lung diseases such as acute respiratory distress syndrome (ARDS) have a high incidence worldwide. The current drug therapies for ARDS have supportive effects, making them inefficient. New methods such as stromal cell therapy are needed for this problem. Methods This research was performed with ten New Zealand rabbits in two groups. Bone marrow aspiration was performed on the treated group, and mesenchymal stem cells were isolated and cultured. The experimental model of ARDS was induced using LPS from Escherichia coli strain O55:B5. Then, 10 10 bone marrow mesenchymal stem cells (BM-MSCs) were autologously transplanted intrapulmonary in the treatment group, and 1–2 ml of PBS in the control group. The clinical signs, computed tomographic (CT) scans, echocardiography, blood gas analysis, complete blood count, and cytokine levels were measured before and at 3, 6, 12, 24, 48, 72, and 168 h after BM-MSC transplant. Finally, the rabbits were killed, and histopathological examination was performed. Results The results showed that BM-MSCs decreased the severity of clinical symptoms, the number of white blood cells and heterophils in the blood, the total cell count, and number of heterophils and macrophages in bronchoalveolar lavage, and balanced the values of arterial blood gases (increase in partial pressure of oxygen and O 2 saturation and decrease in the partial pressure of carbon dioxide). They also downregulated the tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations and increased the IL-10 concentrations at different times compared with time 0 and in the control group, significantly. In the CT scan, a significant decrease in the Hounsfield units and total lung volume was found by echocardiography, and in comparing the two groups, a significant difference in the parameters was noticed. The histopathology demonstrated that the BM-MSCs were able to reduce the infiltration of inflammatory cells and pulmonary hemorrhage and edema. Conclusions This study indicated that BM-MSCs play a significant role in the repair of lung injury.