Polyvalent Vaccine Research Articles

Computational design and evaluation of a polyvalent vaccine for viral nervous necrosis (VNN) in fish to combat Betanodavirus infection

Viral nervous necrosis (VNN) poses a significant threat to the aquaculture industry, causing substantial losses and economic burdens. The disease, attributed to nervous necrosis viruses within the Betanodavirus genus, is particularly pervasive in the Mediterranean region, affecting various fish species across all production stages with mortality rates reaching 100%. Developing effective preventive measures against VNN is imperative. In this study, we employed rigorous immunoinformatics techniques to design a novel multi-epitope vaccine targeting VNN. Five RNA-directed RNA polymerases, crucial to the lifecycle of Betanodavirus, were selected as vaccine targets. The antigenicity and favorable physicochemical properties of these proteins were confirmed, and epitope mapping identified cytotoxic T lymphocyte, helper T lymphocyte, and linear B lymphocyte epitopes essential for eliciting a robust immune response. The selected epitopes, characterized by high antigenicity, non-allergenicity, and non-toxicity, were further enhanced by adding PADRE sequences and hBD adjuvants to increase immunogenicity. Two vaccine constructs were developed by linking epitopes using appropriate linkers, demonstrating high antigenicity, solubility, and stability. Molecular dynamics simulations revealed stable interactions between the vaccine constructs and Toll-like receptors (TLRs), essential for pathogen recognition and immune response activation in fish. Notably, vaccine construct V2 exhibited superior stability and binding affinity with TLR8, suggesting its potential as a promising candidate for VNN prevention. Overall, our study presents a comprehensive approach to VNN vaccine design utilizing immunoinformatics, offering safe, immunogenic, and effective solutions across multiple Betanodavirus species. Further experimental validation in model animals is recommended to fully assess the vaccine’s efficacy. This research contributes to improved vaccine development against diverse fish pathogens by addressing emerging challenges and individualized immunization requirements in aquaculture.

The isolation and serotyping of foot-and-mouth disease virus in Iran during 2019-2022.

Foot-and-mouth disease (FMD) is a significant transboundary animal disease that has a considerable economic impact on livestock systems worldwide. In order to determine the presence and type of FMD virus in Iran, a total of 90 samples of vesicular fluid and epithelial tissue were collected from the tongues, tooth pads, and hooves of clinically suspect cattle on 40 vaccinatedfarms in 9 provinces of Iran. These samples were collected duringfour years, from January 2019 to December 2022, and the vaccine was a locally produced polyvalent inactivated vaccine. The collected samples were analyzed using ELISA and isolation methods to identify and characterize the FMD virus. The results of the ELISA tests revealed that 66.66% of the samples were positive for FMD, and the serotypes of the virus were determined. Considering ELISA reslut, 62% of the samples were assigned to serotype O, 33% to serotype A, and 5% to serotype Asia-1. Furthermore, 90% of the positive samples were inoculated onto monolayer cultures of pig kidneys (IB-RS2) for isolation and antigen detection by serotype-specific ELISA kit. The great majority of detected serotype Oviruses were from Esfahan province, while the most detectedserotype Aand serotype Asia-1 viruses were from Qom and Tehran provinces, respectively. These findings indicate that the ELISA and isolation methods are suitable for identifying and typing FMD viruses. The vaccination program in Iran, which includes three serotypes (O, A, and Asia-1), appears to be effective in controlling the spread of the disease. However, the continued circulation of these serotypes in most provinces suggests that ongoing surveillance and vaccination efforts are necessary.

A study on loading multiple epitopes with a single peptide.

Epitopes, the basic functional units of antigens, hold great significance in the field of immunology. However, the structure and composition of epitopes and their interactions with antibodies remain unclear, which limits in-depth studies on epitopes and the development of subunit vaccines. In a previous study on the localization of anti-influenza HA monoclonal antibodies (mAbs), three strains with different characteristics reacted with the same peptide. In this study, by conventional immunological assays, computer homology modeling, and molecular docking simulations, we found that (1) the peptide could bind to three strains of mAbs with different reaction characteristics utilizing different combinations of immunodominant groups. (2) By computer molecular docking and simulation methods, the immunodominant groups on the two peptides could be combined into a multi-epitope peptide bound to six strains of mAbs. We established a method for multi-epitope peptide recombination from these immunodominant groups. (3) The immune effect of the recombinant multi-epitope peptide was better than that of a single peptide. Our findings facilitate the understanding of the composition of antigen epitopes and provide a theoretical and experimental basis for developing polyvalent vaccines and understanding immune responses at the molecular level.

New Engineered-Chimeric Botulinum Neurotoxin Mutant Acts as an Effective Bivalent Vaccine Against Botulinum Neurotoxin Serotype A and E.

Botulinum neurotoxins (BoNTs), including serotypes A and E, are potent biotoxins known to cause human poisoning. In addition to the critical protective antigen found in the full BoNT molecule, the receptor binding domain (Hc domain), BoNTs also harbour another essential protective antigen-the light chain-translocation domain (L-HN domain). Leveraging these pivotal protective antigens, we genetically engineered a series of inactivated chimeric molecules incorporating L-HN and Hc domains of BoNT/A and E. The structure of these chimeric molecules, mirror BoNT/A and E, but are devoid of enzyme activity. Experimental findings demonstrated that a lead candidate mEL-HN-mAHc harnessing the inactivated protease LCHN/E with the mutated gangliosides binding site Hc/A (mE-mA) elicited robust immune protection against BoNT/A and E simultaneously in a mouse model, requiring low immune dosages and minimal immunisations. Moreover, mE-mA exhibited high protective efficacy against BoNT/A and E in guinea pigs and New Zealand white rabbits, resulting in elevated neutralising antibody titres. Furthermore, mE-mA proved to be a more stable and safer vaccine compared to formaldehyde-inactivated toxoid. Our data underscore the genetically engineered mE-mA as a highly effective bivalent vaccine against BoNT/A and E, paving the way for the development of polyvalent vaccines against biotoxins.

Determination of G and P genotypes of bovine group A rotavirus with emergence of unusual G-and P-type combinations from neonatal calfdiarrhea in Kashmir, India.

A total of 490 diarrhoeic samples from calves aged between 0 and 6 months were screened for the presence of different G- and P-genotypes of rotavirus circulating in bovines in the Kashmir Valley. Of the 490 diarrhoeic samples, Group A rotavirus was detected in 68 (13.87%) samples by polymerase chain reaction (PCR) followed by RNA-PAGE. Genotyping analysis revealed G10, G6, G3, P[11] and P[5] to be the predominant types. The most common types of combinations detected were G10P[11] (27.90%) and G6P[11] (20.60%). The prevalence rate of G10 and P[11] decreased from 60% to 36.76% and 100%-69.11%, respectively. Genotypes G6, G3, P[1] and P[5], which were not previously reported, were detected and unusual combinations such as G6P[11], G3P[11], G10P[5], G3P[5], G6P[1], G6P[5], G6+G8P[11] were also observed for the first time. Fluctuations in the predominant types, emergence of new types and possible genetic reassortment events suggest an unstable epidemiological situation and the need for continuous surveillance of the circulating types to ensure the suitability of the vaccination programme. The present data suggests G10, G6, P[11] and P[5] genotypes could be incorporated in the polyvalent vaccine to offer increased protection against bovine rotavirus infection in India.

A Review of Winter Ulcer Disease and Skin Ulcer Outbreaks in Atlantic Salmon (Salmo salar)

Winter ulcer disease (WUD) is widely recognized as a serious threat to animal welfare and a major contributor to revenue loss within the aquaculture sector, particularly affecting the salmon-farming industry. This highlights the significant impact of WUD on both animal well-being and the economic sustainability of fish farming. WUD causes hemorrhagic signs and results in dermal lesions and ulcers. This disease can lead to higher mortality rates and a considerable decline in the fish’s market value. Moritella viscosa, a Gram-negative bacterium, is predominantly, but not exclusively, correlated with the emergence of WUD, mostly during the colder seasons. Waterborne transmission is the primary way for spreading the bacterium within a population. However, there is remarkable variation in the prevalence and characteristics of WUD in different regions. In Europe, this disease often occurs in the winter, and the intensity and occurrence of outbreaks are influenced by water temperature and salinity. In contrast, outbreaks are typically observed in the summer and mid-autumn in Eastern Canada. Despite the administration of various polyvalent vaccines, outbreaks of skin ulcers have been documented in Canada, and studies have highlighted the possible roles of other bacterial pathogens in Atlantic salmon. This review discusses the etiology, pathogenesis, and potential mitigation or prevention strategies for WUD, mainly in Atlantic salmon. Moreover, it underscores the necessity of conducting further investigations to discover the potential unknown causative agents of ulcerative disease and design appropriate vaccines or preventive strategies for these pathogens.

Formation of adaptive immunity against salmonellosis in cows using effector memory cells

The study aimed to investigate how the number of effector memory cells changes under the influence of a Salmonella vaccine antigen in cows. A homogeneous group of 100 Holstein-Friesian cows, kept under the same conditions, had blood samples taken. The blood was collected at four time points: before the first vaccination, and 7, 45, and 56 days after. The cows also received a booster vaccination on days 8-10. They were immunised with a polyvalent vaccine against livestock salmonellosis in Kazakhstan. Blood was separated into plasma and cellular fractions by centrifugation at 1,500 rpm for 10 minutes. The cellular fraction was then analysed by flow cytometry to determine the number of CD4+, CD8+, and γδ T-cell subpopulations at the four time points: before vaccination, and at 7-, 45-, and 56-days post-vaccination. Analysis of over 10,000 cells from each sample was conducted using FlowJo software. The data showed that the population of CD4+ and CD8+ T-lymphocytes and γδ T-cells increased 1.5 times by day 7 after the initial vaccination. The cows then received a booster dose on days 8-10, and by day 45 after the first vaccination, the CD4+ and CD8+ T-lymphocyte and γδ T-cell populations had increased threefold. CD45RA+ T-lymphocytes and γδ T-cells demonstrated a steady increase by day 45, followed by a decline in the numbers of T-cells across all phylogenetic groups. Thus, it can be concluded that the primary vaccination stimulates the development of long-term immune memory, while the booster dose triples the number of CD4+, CD8+, and γδ T-cell subpopulations. The findings provide insights into the mechanism of adaptive immunity formation in cows against salmonellosis through the use of effector memory cells and may be applied in developing vaccination strategies for cattle

Immunogenicity of a pentavalent recombinant Escherichiacoli bacterin against enterotoxemia and botulism in sheep

IntroductionProducing commercial bacterins/toxoids against Clostridium spp. is laborious and hazardous. Conversely, developing prototype vaccines using purified recombinant toxoids, though safe and effective, is both laborious and costly for application in production animals. ObjectiveConsidering that inactivated recombinant Escherichiacoli (bacterin) is a simple, cost-effective, and to be safe solution, we evaluated, for the first time, a pentavalent formulation of recombinant bacterins containing the alpha, beta, and epsilon toxins of Clostridiumperfringens and C and D neurotoxins of Clostridiumbotulinum in sheep. MethodsSubcutaneously, 18 Texel sheep received two doses (200 μg of each antigen) of recombinant bacterin (n = 7) or purified recombinant antigens (n = 6) on days 0 and 28, while the control group (n = 5) did not receive an immunization. Sera samples from days 0 (before the 1st dose), 28 (before the 2nd dose), and 56, 84, and 112 were used for measuring IgG (indirect ELISA) and neutralizing antibodies (mouse serum neutralization). ResultsBoth formulations induced significant levels of IgG against all five toxins (p < 0.05) up to day 112, with peaks at days 28 and 56 post-immunization. The expected booster effect occurred only for the botulinum toxins. The neutralizing antibody titers were satisfactory against ETX (≥2 IU/ml for both formulations) and BoNT-D [5 IU/ml (bacterin) and 10 IU/ml (purified)]. ConclusionWhile adjustments are required, the recombinant bacterin platform holds great potential for polyvalent vaccines due to its straightforward, safe, and cost-effective production, establishing it as a user-friendly technology for the veterinary immunobiological industry.

Molecular characteristics of the structure protein VP1 in Coxsackievirus A10 Isolates from China.

Coxsackievirus A10 (CVA10) is a non-enveloped, positive-sense single-stranded RNA virus classified within the Enterovirus genus in the Picornaviridae family. It is among the pathogens that can cause hand, foot and mouth disease. This study aimed to analyze the temporal and spatial distribution of CVA10 in China to understand its epidemiological characteristics of CVA10. We collected the VP1 sequences of CVA10 from January 1, 2004, to December 31, 2019, from the GenBank database and created the global map using MapChart. We selected 56 known CVA10 genotype sequences. Then, MEGA6.06 was used to construct a phylogenetic tree with the collected gene sequences and the known reference sequences for comparative analysis to assess the distribution of CVA10 genotypes in different countries between 2004 and 2019. CVA10 has been widely detected or reported globally. In China, the prevalent genotype of CVA10 was mainly genotype B before 2008 and genotype C after 2009. In other countries, the prevalence of genotype D was dominant, followed by genotypes C and F, and the prevalence of CVA10 varied from continent to continent. Monitoring CVA10 genotypes or evolutionary branches should be strengthened, and the study of epidemic genotype characteristics should be enhanced. This will serve as a basis for further research and development of monovalent CVA10 or polyvalent vaccines designed for effective disease prevention.

Differential polyvalent passive immune protection of egg yolk antibodies (IgY) against live and inactivated Vibrio fluvialis in fish

Egg yolk antibodies (IgY) can be prepared in large quantities and economically, and have potential value as polyvalent passive vaccines (against multiple bacteria) in aquaculture. This study prepared live and inactivated Vibrio fluvialis IgY and immunized Carassius auratus prior to infection with V. fluvialis and Aeromonas hydrophila. The results showed that the two IgY antibodies hold effective passive protective rates against V. fluvialis and A. hydrophila in C. auratus. Further, the serum of C. auratus recognized the two bacteria in vitro, with a decrease in the bacteria content of the kidney. The phagocytic activity of C. auratus plasma was enhanced, with a decrease in the expression of inflammatory and antioxidant factors. Pathological sections showed that the kidney, spleen, and intestinal tissue structures were intact, and apoptosis and DNA damage decreased in kidney cells. Moreover, the immunoprotection conferred by the live V. fluvialis IgY was higher than that of the inactivated IgY. Addition, live V. fluvialis immunity induced IgY antibodies against outer membrane proteins of V. fluvialis were more than inactivated V. fluvialis immunity. Furthermore, heterologous immune bacteria will not cause infection, so V. fluvialis can be used to immunize chickens to obtain a large amount of IgY antibody. These findings suggest that the passive immunization effect of live bacterial IgY antibody on fish is significantly better than that of inactivated bacterial antibody, and the live V. fluvialis IgY hold potential value as polyvalent passive vaccines in aquaculture.

Memory T-cell dynamics following immunization with a polyvalent salmonellosis vaccine in farm animals

Memory T-cell dynamics following immunization with a polyvalent salmonellosis vaccine in farm animals

Formulation of next-generation polyvalent vaccine candidates against three important poxviruses by targeting DNA-dependent RNA polymerase using an integrated immunoinformatics and molecular modeling approach

BackgroundPoxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus (MPXV; formerly Monkeypox), variola virus (VARV), and volepox virus (VPXV) are among the prevalent poxviruses of the Orthopoxviridae genera. The ongoing Mpox infectious disease pandemic caused by the Mpox virus has had a major impact on public health across the globe. To date, only limited repurposed antivirals and vaccines are available for the effective treatment of Mpox and other poxviruses that cause contagious diseases. MethodsThe present study was conducted with the primary goal of formulating multi-epitope vaccines against three evolutionary closed poxviruses i.e., MPXV, VARV, and VPXV using an integrated immunoinformatics and molecular modeling approach. DNA-dependent RNA polymerase (DdRp), a potential vaccine target of poxviruses, has been used to determine immunodominant B and T-cell epitopes followed by interactions analysis with Toll-like receptor 2 at the atomic level. ResultsThree multi-epitope vaccine constructs, namely DdRp_MPXV (V1), DdRp_VARV (V2), and DdRp_VPXV (V3) were designed. These vaccine constructs were found to be antigenic, non-allergenic, non-toxic, and soluble with desired physicochemical properties. Protein-protein docking and interaction profiling analysis depicts a strong binding pattern between the targeted immune receptor TLR2 and the structural models of the designed vaccine constructs, and manifested a number of biochemical bonds (hydrogen bonds, salt bridges, and non-bonded contacts). State-of-the-art all-atoms molecular dynamics simulations revealed highly stable interactions of vaccine constructs with TLR2 at the atomic level throughout the simulations on 300 nanoseconds. Additionally, the outcome of the immune simulation analysis suggested that designed vaccines have the potential to induce protective immunity against targeted poxviruses. ConclusionsTaken together, formulated next-generation polyvalent vaccines were found to have good efficacy against closely related poxviruses (MPXV, VARV, and VPXV) as demonstrated by our extensive immunoinformatics and molecular modeling evaluations; however, further experimental investigations are still needed.

In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses.

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox virus pose a significant threat to public health, and effective prevention and treatment strategies are needed. This study utilized a reverse vaccinology approach to retrieve conserved epitopes for monkeypox virus and construct a vaccine that could provide cross-protection against related viruses with similar antigenic properties. The selected virulent proteins of monkeypox virus, MPXVgp165, and Virion core protein P4a, were subjected to epitope mapping for vaccine construction. Two vaccines were constructed using selected T cell epitopes and B cell epitopes with PADRE and human beta-defensins adjuvants conjugated in the vaccine sequence. Both constructs were found to be highly antigenic, non-allergenic, nontoxic, and soluble, suggesting their potential to generate an adequate immune response and be safe for humans. Vaccine construct 1 was selected for molecular dynamic simulation studies. The simulation studies revealed that the TLR8-vaccine complex was more stable than the TLR3-vaccine complex. The lower RMSD and RMSF values of the TLR8 bound vaccine compared to the TLR3 bound vaccine suggested better stability and consistency of hydrogen bonds. The Rg values of the vaccine chain bound to TLR8 indicated overall stability, whereas the vaccine chain bound to TLR3 showed deviations throughout the simulation. These results suggest that the constructed vaccine could be a potential preventive measure against monkeypox and related viruses however, further experimental validation is required to confirm these findings.

Gamma Irradiated Pasteurella multocida Vaccine induces strong humoral immunity and protects rabbits from disease

Pasteurella multocida is affecting a multitude of animals and severely affects livestock production. Existing vaccines are mostly chemically inactivated and do not lead to wide protection. Irradiated vaccines are enjoying a renaissance and the concept of “replication defficient but metabolically active” vaccines was recently evaluated in several vaccine trials. P. multocida was isolated from the nasal swab, blood, and lung swab samples from infected rabbits. Gamma irradiation of P. multocida for inhibition of replication was evaluated at an optimized irradiation dose of 10 Kgy established. Four groups of rabbits were (mock) vaccinated with a commercial P. multocida vaccine and three irradiated formulations as liquid, lyophilized formulations with added Trehalose and lyophilized-Trehalose with an “activation” culturing the irradiated bacteria for 24 in broth. Evaluation of humoral immune response by ELISA showed that all three irradiated vaccines produced an effective, protective, and continued IgG serum level after vaccination and bacterial challenge. The IFN-γ expression is maintained at a normal level, within each individual group however, the lyophilized trehalose irradiated vaccine showed peak mean of IFN-γ titer at one week after booster dose (day 21) which was statistically significant. Cumulatively, the results of this study show that gamma-irradiated P. multocida vaccines are safe and protect rabbits against disease. Moreover, Rabbits’ immunization with the three irradiated formulations avoided adverse side effects as compared to commercial polyvalent vaccine, the body weight gain for the irradiated vaccine groups indicates less stress compared to the commercial polyvalent vaccine.

Characterization of human papillomavirus genotypes and their coverage in vaccine delivered to Ethiopian women

Cervical cancer is a significant public health concern in Ethiopia. It is mainly caused by persistent infection with the human papillomaviruses. The aim of this study was to assess the relationship between carcinogenic risk of probable, possible and low risk HPV infection and those of cervical intraepithelial neoplasia (CIN) and cervical cancer. A cross sectional study nested from prospective cohort study was conducted in Bahir Dar, northwest Ethiopia. Statistical analyses were performed using SPSSversion 26.0. HPV-16 was associated with a relatively higher risk of CIN II+, (AOR = 15.42; 95% CI 6.81–34.91). In addition, HPV-52, -18, -53 and -58, were significantly associated with an increased risk of CIN II+, (AOR = 7.38 (1.73–31.54), 5.42 (1.61–18.31), 4.08 (1.53–10.87), and 3.17 (1.00–10.03)), respectively. The current study shows high rate of HPV with predominance of HPV-16, -53, -58, -18, -35, and -52. The quadrivalent and nonavalent vaccine had only covered 27.1% and 45% of the circulating HPV genotypes. Ethiopia may need to consider introduction of nonavalent vaccine into the national public health strategy. Polyvalent vaccine which includes the genotypes not covered by existing approved vaccines should be considered.

Recent advances on vaccines against malaria: A review

This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines. Data on malaria vaccine development was collected through a comprehensive review. The literature search was performed using databases including Google Scholar, PubMed, NIH, and Web of Science. Various novel approaches of vaccination are being developed, including those based on radiation-attenuated strategies, monoclonal antibodies, targeted immunogenic peptides, RNA and DNA vaccines, nanoparticle-based vaccines, protein-based vaccination protocols, and whole organism-based vaccination strategies. Trials on RTS, S have entered phase III testing, and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials. Mathematical modeling, combined drug and vaccine strategies, mass drug administration, polyvalent vaccine formulations, and targeted vaccination campaigns is playing an important role in malarial prevention. Furthermore, assessing coverage, accessibility, acceptability, deployment, compilation, and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.

Evaluation of Two Vaccines against Foot-and-Mouth Disease Used in Transcaucasian Countries by Small-Scale Immunogenicity Studies Conducted in Georgia, Azerbaijan and Armenia.

In countries endemic for foot-and-mouth disease (FMD), routine or emergency vaccinations are strategic tools to control the infection. According to the WOAH/FAO guidelines, a prior estimation of vaccine effectiveness is recommendable to optimize control programs. This study reports the results of a small-scale immunogenicity study performed in Transcaucasian Countries. Polyvalent vaccines, including FMDV serotypes O, A (two topotypes) and Asia1 from two different manufacturers, were evaluated in Georgia, Azerbaijan and Armenia. Naïve large and small ruminants were vaccinated once and a subgroup received a second booster dose. The titers of neutralizing antibodies in sera collected sequentially up to 180 DPV were determined through the Virus Neutralization Test versus homologous strains. This study led to the estimate that both the vaccines evaluated will not induce a protective and long-lasting population immunity, even after a second vaccination, stressing that consecutive administrations of both vaccines every three months are mandatory if one aspires to achieve protective herd immunity.

Evaluation of protective efficacy, serological responses, and cytokine modulation induced by polyvalent Leptospira vaccines in hamsters

Whole-cell inactivated vaccines (bacterins) are the only licensed vaccines available for leptospirosis prevention and control, especially in domestic and farm animals. However, despite their widespread use, inconsistencies in their efficacy have been reported. Because immunity induced by bacterins is mainly mediated by antibodies against leptospiral lipopolysaccharides, the involvement of cellular responses is not well-known. The aim of this study was to investigate the efficacy and characterize the humoral and cellular immune responses induced by whole-cell inactivated leptospirosis bacterin formulations containing serovars Bratislava, Canicola, Copenhageni, Grippotyphosa, Hardjoprajitno, and Pomona. For the potency test, hamsters were immunized with one dose of polyvalent bacterins (either commercial or experimental) and then challenged with a virulent Pomona strain. Serological (MAT and IgM and IgG-ELISA) and cellular (cytokine transcription in blood evaluated by RT-qPCR) analyses were performed. The results revealed that vaccination with either bacterin formulation was able to protect 90–100% of the hamsters infected with the Pomona serovar, although most of the surviving animals remained as renal carriers. Specific agglutinating antibodies and significant levels of IgM, IgG, and IgG2 (P < 0.05) that were able to react with the six serovars present in the vaccine formulations were produced, indicating that the vaccines can potentially provide immunity against all strains. The protective immunity of these vaccines was mainly mediated by balanced a Th1/Th2 response, characterized by increased IFN-γ, IL-10 and IL-α transcription. These data support the importance of characterizing immunological responses involved in bacterin efficacy and investing in the improvement of these vaccine formulations.

A polyvalent RNA vaccine reduces the immune imprinting phenotype in mice and induces neutralizing antibodies against omicron SARS-CoV-2

Immune imprinting is now evident in COVID-19 vaccinated people. This phenomenon may impair the development of effective neutralizing antibodies against variants of concern (VoCs), mainly Omicron and its subvariants. Consequently, the boost doses with bivalent vaccines have not shown a significant gain of function regarding the neutralization of Omicron. The approach to design COVID-19 vaccines must be revised to improve the effectiveness against VoCs. Here, we took advantage of the self-amplifying characteristic of RepRNA and developed a polyvalent formulation composed of mRNA from five VoCs. LION/RepRNA Polyvalent induced neutralizing antibodies in mice previously immunized with LION/RepRNA D614G and reduced the imprinted phenotype associated with low neutralization capacity of Omicron B.1.1.529 pseudoviruses. The polyvalent vaccine can be a strategy to handle the low neutralization of Omicron VoC, despite booster doses with either monovalent or bivalent vaccines.

Effect of two different commercial vaccines against bovine respiratory disease on cell-mediated immunity in Holstein cattle.

Bovine respiratory disease (BRD) is a complex illness that impacts the respiratory system of domestic cattle, resulting in significant financial losses for the agriculture industry. Inactivated or modified live (MLV) pathogen vaccines are often used as a management tool to prevent and control BRD effectively. The purpose of this study is to assess the cell-mediated immune response (CMI) induced by two commercially available polyvalent vaccines, namely the MLV (cattle master gold FP) and the inactivated (CATTLEWIN-5K) vaccine. A total of 20 seronegative heifers against 4 BRD viruses, bovine alphaherpisvirus-1 (BoAHV-1), bovine viral diarrhea virus (BVDV BVDV-1: Pesti virus A; BVDV-2: Pesti virus B), bovine respiratory syncytial virus (BRSV) and bovine parainfluenza virus-3 (BPIV3) were chosen for this study. The heifers were divided into three groups. The first group (n = 6) received no vaccination and was kept as a control. The second and third groups (seven heifers each) were vaccinated twice with either an MLV or inactivated vaccine. The gene expression level of interleukin-6 (IL-6) and interferon-gamma (INF-γ) was measured using real-time quantitative polymerase chain reaction on the 7th, 14th, 21st, 28th, and 60th days post-vaccination. The results were compared with the control group to study the effectiveness of the vaccines. There was an upregulation in the expression level of IL-6 and INF-γ in both MLV and inactivated vaccinated groups. The level of IL-6 mRNA expression was statistically increased from the 14th and 28th days post-vaccination in MLV and inactivated vaccine groups, respectively. The expression level of INF-γ increased significantly from the 2nd and 4th weeks post-vaccination in the MLV and inactivated vaccine groups, respectively. The mean expression level of IL-6 and INF-γ mRNAs was significantly higher in the MLV vaccine group than in the inactivated vaccine group at each examination time. Both investigated vaccines are efficient in stimulating CMI, particularly with the MLV vaccine showing a higher preponderance in IL-6 and INF-γ.