RESUMEN
BACKGROUND: Klebsiella pneumoniae (KP), responsible for acute lung injury (ALI) and inflammation of the gastrointestinal tract, is a zoonotic pathogen that poses a threat to livestock farming worldwide. Nevertheless, there is currently no validated vaccine to prevent KP infection. The development of mucosal vaccines against KP using Lactobacillus plantarum (L. plantarum) is an effective strategy. RESULTS: Firstly, the L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c were constructed via homologous recombination to express the aCD11c protein either inducibly or constitutively. Both NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c strains could enhance the adhesion and invasion of L. plantarum on bone marrow-derived dendritic cells (BMDCs), and stimulate the activation of BMDCs compared to the control strain NC8-pSIP409 in vitro. Following oral immunization of mice with NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c, the cellular, humoral, and mucosal immunity were significantly improved, as evidenced by the increased expression of CD4+ IL-4+ T cells in the spleen, IgG in serum, and secretory IgA (sIgA) in the intestinal lavage fluid (ILF). Furthermore, the protective effects of L. plantarum against inflammatory damage caused by KP infection were confirmed by assessing the bacterial loads in various tissues, lung wet/dry ratio (W/D), levels of inflammatory cytokines, and histological evaluation, which influenced T helper 17 (Th17) and regulatory T (Treg) cells in peripheral blood and lung. CONCLUSIONS: Both the inducible and constitutive L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c have been found to stimulate cellular and humoral immunity levels and alleviate the inflammatory response caused by KP infection. These findings have provided a basis for the development of a novel vaccine against KP.
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Inmunidad Celular , Infecciones por Klebsiella , Klebsiella pneumoniae , Lactobacillus plantarum , Animales , Infecciones por Klebsiella/prevención & control , Infecciones por Klebsiella/veterinaria , Infecciones por Klebsiella/inmunología , Klebsiella pneumoniae/inmunología , Ratones , Administración Oral , Femenino , Ratones Endogámicos BALB C , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Células Dendríticas/inmunología , InflamaciónRESUMEN
INTRODUCTION: Clostridioides difficile (C.diff) infection (CDI) causes significant morbidity and mortality among older adults. Vaccines to prevent CDI are in development; however, data on the target population's preferences are needed to inform vaccination recommendations in the United States (US). This study assessed US adults' willingness to receive a C.diff vaccine and examined how vaccine attributes influence their choices. METHODS: A cross-sectional online survey with a discrete choice experiment (DCE) was conducted among US adults aged ≥50 years. DCE attributes included effectiveness, duration of protection, reduction in symptom severity, out-of-pocket (OOP) costs, number of doses, and side effects. The DCE included 11 choice tasks, each with two hypothetical vaccine profiles and an opt-out (i.e., no vaccine). Attribute-level preference weights were estimated using hierarchical Bayesian modeling. Attribute relative importance (RI) was compared between select subgroups. RESULTS: Of 1216 adults in the analyses, 29.9% reported they knew either 'a little' (20.7%) or 'a lot' (9.2%) about C.diff before the study. A C.diff vaccine was chosen 58.0% of the time (vs. opt-out) across choice tasks. It was estimated that up to 75.0% would choose a vaccine when OOP was $0. Those who were immunocompromised/high-risk for CDI (vs. not) more frequently chose a C.diff vaccine. Decreases in OOP costs (RI = 56.1), improvements in vaccine effectiveness (RI = 17.7), and reduction in symptom severity (RI = 10.3) were most important to vaccine choice. The rank ordering of attributes by importance was consistent across subgroups. CONCLUSION: OOP cost, improvements in vaccine effectiveness, and reduction in CDI severity were highly influential to vaccine selection. Most adults aged ≥50 years were receptive to a C.diff vaccine, especially with little-to-no OOP cost, suggesting that mandating insurance coverage of vaccination with no copayment may increase uptake. The limited awareness about C.diff among adults presents an opportunity for healthcare providers to educate their patients about CDI prevention.
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Vacunas Bacterianas , Clostridioides difficile , Infecciones por Clostridium , Humanos , Persona de Mediana Edad , Femenino , Estados Unidos , Masculino , Infecciones por Clostridium/prevención & control , Estudios Transversales , Anciano , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/economía , Clostridioides difficile/inmunología , Vacunación/psicología , Prioridad del Paciente/estadística & datos numéricos , Encuestas y Cuestionarios , Anciano de 80 o más Años , Teorema de BayesRESUMEN
Syphilis, caused by Treponema pallidum subsp. pallidum, is a global health concern with increasing rates worldwide. Current prevention strategies, including screen-and-treat approaches, are not sufficient to resolve rising infection rates, emphasizing the need for a vaccine. Developing a syphilis vaccine necessitates a range of cross-disciplinary considerations, including essential disease-specific protection, technical requirements, economic feasibility, manufacturing constraints, public acceptance, equitable vaccine access, alignment with global public vaccination programs, and identification of essential populations to be vaccinated to achieve herd immunity. Central to syphilis vaccine development is prioritization of global vaccine availability, including access in low- to middle-income settings. Various vaccine platforms, including subunit, virus-like particle (VLP), mRNA, and outer membrane vesicle (OMV) vaccines, present both advantages and challenges. The proactive consideration of both manufacturing feasibility and efficacy throughout the pre-clinical research and development stages is essential for producing an efficacious, inexpensive, and scalable syphilis vaccine to address the growing global health burden caused by this disease.
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Vacunas Bacterianas , Sífilis , Treponema pallidum , Desarrollo de Vacunas , Sífilis/prevención & control , Sífilis/inmunología , Humanos , Treponema pallidum/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Salud Global , Animales , Vacunas de Partículas Similares a Virus/inmunologíaRESUMEN
Bacterial septicemia represents a significant disease affecting cultured grass carp culture, with the primary etiological agent identified as the Gram-negative bacterium Aeromonas veronii. In response to an outbreak of septicemia in Guangzhou, we developed a formaldehyde-inactivated vaccine against an A. veronii strain designated AV-GZ21-2. This strain exhibited high pathogenicity in experimental infections across at all developmental stages of grass carp. Mortality rates for grass carp weighing 15 ± 5 g ranged from 16 % to 92 % at exposure temperatures of 19 °C-34 °C, respectively. The median lethal dose (LD50) for grass carp groups weighing 15 ± 5 g, 60 ± 10 g, 150 ± 30 g and 500 ± 50 g were determined to be 1.43, 2.52, 4.65 and 7.12 × 107(CFU/mL), respectively. We investigated the inactivated vaccine in conbination with aluminum hydroxide gel (AV-AHG), Montanide ISA201VG (AV-201VG), and white oil (AV-WO) adjuvants. This study aimed to optimize inactivation conditions and identify the adjuvant that elicits the most robust immune response. The AV-GZ21-2 inactivated bacterial solution (AV),when combined with various adjuvants, was capable of inducing a strong specific immune response in grass carp. The relative percent survival (RPS) following a lethal challenge with AV-GZ21-2 were 94 % for AV-AHG, 88 % for AV-201VG, 84 % for AV-WO and 78 % for AV alone. The minimum immunization dose of the AV-AHG vaccine was determined to be 6.0 × 107 CFU per fish, providing immunity for a duration of six months with an immune protection level exceeding 75 %. Furthermore, the AV-AHG vaccine demonstrated significant protective efficacy against various epidemic isolates of A. veronii. Consequently, we developed an inactivated vaccine targeting a highly pathogenic strain of A. veronii, incorporating an aluminum hydroxide gel adjuvant, which resulted in high immune protection and a duration of immunity exceeding six months. These findings suggest that the AV-AHG vaccine holds substantial potential for industrial application.
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Adyuvantes Inmunológicos , Aeromonas veronii , Vacunas Bacterianas , Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Vacunas de Productos Inactivados , Animales , Carpas/microbiología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Aeromonas veronii/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/inmunología , Virulencia , Adyuvantes Inmunológicos/administración & dosificación , Dosificación Letal Mediana , Temperatura , China/epidemiología , Hidróxido de Aluminio/administración & dosificaciónRESUMEN
Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted by Ixodes spp ticks. The rise in Lyme disease cases since its discovery in the 1970s has reinforced the need for a vaccine. A vaccine based on B burgdorferi outer surface protein A (OspA) was approved by the Food and Drug Administration (FDA) several decades ago, but was pulled from the market a few years later, reportedly due to poor sales, despite multiple organizations concluding that it was safe and effective. Newer OspA-based vaccines are being developed and are likely to be available in the coming years. More recently, there has been a push to develop vaccines that target the tick vector instead of the pathogen to inhibit tick feeding and thus prevent transmission of tick-borne pathogens to humans and wildlife reservoirs. This review outlines the history of Lyme disease vaccines and this movement to anti-tick vaccine approaches.
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Borrelia burgdorferi , Ixodes , Vacunas contra Enfermedad de Lyme , Enfermedad de Lyme , Enfermedad de Lyme/prevención & control , Enfermedad de Lyme/inmunología , Humanos , Animales , Borrelia burgdorferi/inmunología , Vacunas contra Enfermedad de Lyme/inmunología , Ixodes/microbiología , Vacunación , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Antígenos de Superficie/inmunología , Lipoproteínas/inmunologíaRESUMEN
Klebsiella pneumoniae is a primary cause of clinical mastitis in dairy cows, with prevention being crucial, as treatments often fail due to antimicrobial resistance. Recent studies identified type I fimbrial antigens of K. pneumoniae as promising vaccine candidates, but there are limited research data. In this study, 3 fimbriae genes (fimA, fimC and fimG) were cloned and recombinantly expressed in Escherichia coli and their protective efficacy against K. pneumoniae evaluated in a mouse model. All 3 recombinant fimbriae proteins elicited strong humoral immune responses in mice, significantly increasing IgG, IgG1 and IgG2a. Notably, using a model of mice challenged with an intraperitoneal injection of bacteria, FimG significantly reduced bacterial loads in the spleen and lung, whereas FimA and FimC had limited protection for these organs. Either active or passive immunization with FimG produced substantial protective effects in mice challenged with K. pneumoniae LD100; in contrast, the mortality rate in the FimA-immunized group was similar to that of the control group, whereas FimC had weak protection. We concluded that the FimG recombinant protein vaccine had a favorable protective effect, with potential for immunization against K. pneumoniae mastitis.
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Anticuerpos Antibacterianos , Vacunas Bacterianas , Modelos Animales de Enfermedad , Proteínas Fimbrias , Infecciones por Klebsiella , Klebsiella pneumoniae , Ratones Endogámicos BALB C , Animales , Klebsiella pneumoniae/inmunología , Ratones , Infecciones por Klebsiella/prevención & control , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/microbiología , Proteínas Fimbrias/inmunología , Proteínas Fimbrias/genética , Femenino , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Proteínas Recombinantes/inmunología , Fimbrias Bacterianas/inmunología , Inmunoglobulina G/sangre , Inmunidad HumoralRESUMEN
INTRODUCTION: Chickens with Necrotic Enteritis (NE), caused by Clostridium perfringens, exhibit acute and chronic symptoms that are difficult to diagnose, leading to significant economic losses. Vaccination is the best method for controlling and preventing NE. However, only two vaccines based on the CPA and NetB toxins have been commercialized, offering partial protection, highlighting the urgent need for more effective vaccines. OBJECTIVE: This review aimed to identify promising antigens for NE vaccine formulation and discuss factors affecting their effectiveness. METHODS: A systematic review using five scientific databases identified 30 eligible studies through the Rayyan tool, which were included for quality review. RESULTS: We identified 25 promising antigens, including CPA, NetB, FBA, ZMP, CnaA, FimA, and FimB, categorized by their role in disease pathogenesis. This review discusses the biochemical, physiological, and genetic traits of recombinant antigens used in vaccine prototypes, their expression systems, and immunization potential in chickens challenged with virulent C. perfringens strains. Market supply challenges, immunogenic potential, vaccine platforms, adjuvants, and factors related to vaccination schedules-such as administration routes, dosing intervals, and age at immunization-are also addressed. Additionally, the study notes that vaccine formulations tested under mild challenges may not offer adequate field-level protection due to issues replicating aggressive conditions, strain virulence loss, and varied methodologies. CONCLUSIONS: An ideal NE vaccine should incorporate multiple antigens, molecular adjuvants, and delivery systems via in ovo and oral routes. The review underscores the challenges in developing and validating NE vaccines and the urgent need for a standardized protocol to replicate aggressive challenges accurately.
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Vacunas Bacterianas , Pollos , Infecciones por Clostridium , Clostridium perfringens , Enteritis , Enfermedades de las Aves de Corral , Animales , Clostridium perfringens/inmunología , Clostridium perfringens/genética , Enteritis/prevención & control , Enteritis/veterinaria , Enteritis/microbiología , Enteritis/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/microbiología , Infecciones por Clostridium/prevención & control , Infecciones por Clostridium/veterinaria , Infecciones por Clostridium/inmunología , Antígenos Bacterianos/inmunología , Desarrollo de Vacunas/métodos , Vacunación/veterinaria , Vacunación/métodos , Necrosis/veterinariaRESUMEN
INTRODUCTION: Producing 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. OBJECTIVE: Considering 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. METHODS: Subcutaneously, 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). RESULTS: Both 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)]. CONCLUSION: While 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.
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Anticuerpos Antibacterianos , Anticuerpos Neutralizantes , Vacunas Bacterianas , Botulismo , Enterotoxemia , Animales , Botulismo/prevención & control , Botulismo/veterinaria , Botulismo/inmunología , Ovinos , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/genética , Anticuerpos Antibacterianos/sangre , Enterotoxemia/prevención & control , Enterotoxemia/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Enfermedades de las Ovejas/prevención & control , Enfermedades de las Ovejas/inmunología , Enfermedades de las Ovejas/microbiología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Inmunoglobulina G/sangre , Escherichia coli/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , FemeninoRESUMEN
INTRODUCTION: Clostridioides difficile is the main cause of antibiotic-associated diarrhea in humans and is a major enteropathogen in several animal species. In newborn piglets, colonic lesions caused by C. difficile A and B toxins (TcdA and TcdB, respectively) cause diarrhea and significant production losses. OBJECTIVE: The present study aimed to develop two recombinant vaccines from immunogenic C-terminal fragments of TcdA and TcdB and evaluate the immune response in rabbits and in breeding sows. Two vaccines were produced: bivalent (rAB), consisting of recombinant fragments of TcdA and TcdB, and chimeric (rQAB), corresponding to the synthesis of the same fragments in a single protein. Groups of rabbits were inoculated with 10 or 50 µg of proteins adjuvanted with aluminum or 0.85 % sterile saline in a final volume of 1 mL/dose. Anti-TcdA and anti-TcdB IgG antibodies were detected in rabbits and sows immunized with both rAB and rQAB vaccines by ELISA. The vaccinated sows were inoculated intramuscularly with 20 µg/dose using a prime-boost approach. RESULTS: Different antibody titers (p ≤ 0.05) were observed among the vaccinated groups of sows (rAB and rQAB) and control. Additionally, newborn piglets from vaccinated sows were also positive for anti-TcdA and anti-TcdB IgGs, in contrast to control piglets (p ≤ 0.05). Immunization of sows with the rQAB vaccine conferred higher anti-TcdA and anti-TcdB responses in piglets, suggesting the superiority of this compound over rAB. CONCLUSION: The synthesized recombinant proteins were capable of inducing antibody titers against C. difficile toxins A and B in sows, and were passively transferred to piglets through colostrum.
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Animales Recién Nacidos , Anticuerpos Antibacterianos , Toxinas Bacterianas , Vacunas Bacterianas , Clostridioides difficile , Infecciones por Clostridium , Enfermedades de los Porcinos , Vacunas Sintéticas , Animales , Femenino , Porcinos , Conejos , Infecciones por Clostridium/prevención & control , Infecciones por Clostridium/veterinaria , Infecciones por Clostridium/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/genética , Embarazo , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Clostridioides difficile/inmunología , Clostridioides difficile/genética , Anticuerpos Antibacterianos/sangre , Toxinas Bacterianas/inmunología , Toxinas Bacterianas/genética , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/genética , Enterotoxinas/inmunología , Enterotoxinas/genéticaRESUMEN
Pseudomonas plecoglossicida is one of most important pathogenic bacterial species in large yellow croaker and several other commercially valuable fish species. In our previous study, a GacS deficient mutant (ΔgacS) was constructed and its virulence showed substantially attenuated. In present study, the safety, immunogenicity and protective effect of the ΔgacS were evaluated in large yellow croaker as a live-attenuated vaccine candidate. It was shown that the ΔgacS strain exhibited good safety to large yellow croaker and there was no mortality or clinical symptoms observed in all fish that infected by ΔgacS strain with the doses range from 2 × 105ï½107 CFU per fish via intraperitoneal injection (IP) or immersion (IM), and almost all bacteria were cleaned up in the spleen of the fish at 14-day post infection. Specific antibodies could be detected at 7-day and 14-day post infection by direct agglutination method, and the valences of antibodies and bactericidal activities of the serum were significant increased with vaccination doses and vaccination time. Moreover, the expressions of some molecules and cytokines involved in specific immune responses were detected in the ΔgacS strain immunization group and control group. After challenged by the wild-type (WT) strain XSDHY-P, the relative percentage survival (RPS) showed highly correlated with the immunized dosage regardless of vaccination methods. It showed that the RPS of the IP groups were 39.47 %, 57.89 %, 71.05 % with the immune dosage in a descending order, respectively, and the RPS of the IM groups were 26.31 %, 36.84 %, 76.31 % with the immune dosage in a descending order, respectively. In summary, the ΔgacS strain exhibited safety and good protective effect to large yellow croaker and was a potential live vaccine candidate.
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Enfermedades de los Peces , Perciformes , Infecciones por Pseudomonas , Pseudomonas , Vacunas Atenuadas , Animales , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/prevención & control , Perciformes/inmunología , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/administración & dosificación , Infecciones por Pseudomonas/veterinaria , Infecciones por Pseudomonas/prevención & control , Infecciones por Pseudomonas/inmunología , Pseudomonas/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas contra la Infección por Pseudomonas/inmunología , Vacunas contra la Infección por Pseudomonas/genética , Inmunogenicidad VacunalRESUMEN
Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen and the major cause of healthcare-associated infections, which are increasingly complicated by the prevalence of highly invasive and hyper-virulent K. pneumoniae strains, necessitating the development of alternative strategies for combatting infections caused by this bacterium. In this study, we successfully constructed a fusion antigen called KP-Ag1, comprising three antigens (GlnH, FimA, and KPN_00466) that were previously identified through reverse vaccinology. Immunization with KP-Ag1 formulated with Al(OH)3 adjuvant elicited robust humoral and cellular immune response in mice, and conferred protective immunity in a murine model of K. pneumoniae lung infection. Further analysis of serum IgG subtypes from mice immunized with KP-Ag1 revealed a predominant IgG1 response, indicating that KP-Ag1 predominantly induces a Th2-biased immune response. Additionally, opsonophagocytic killing assay suggested that humoral immune responses play a pivotal role in mediating protection conferred by KP-Ag1. Moreover, KP-Ag1 was found to promote the activation and maturation of BMDCs in vitro, which is essential for subsequent efficient antigen presentation. More importantly, vaccination with KP-Ag1 demonstrated cross-protective efficacy against clinical isolates of K. pneumoniae varying in serotypes, antibiotic resistance, and virulence profiles. Therefore, KP-Ag1 holds promise as a candidate for K. pneumoniae vaccine development.
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Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Vacunas Bacterianas , Modelos Animales de Enfermedad , Inmunoglobulina G , Infecciones por Klebsiella , Klebsiella pneumoniae , Animales , Klebsiella pneumoniae/inmunología , Infecciones por Klebsiella/prevención & control , Infecciones por Klebsiella/inmunología , Ratones , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Femenino , Inmunidad Humoral , Vacunación/métodos , Antígenos Bacterianos/inmunología , Neumonía Bacteriana/prevención & control , Neumonía Bacteriana/inmunología , Ratones Endogámicos BALB C , Inmunidad Celular , Protección Cruzada/inmunologíaRESUMEN
Sheep farming contributes to the socioeconomic development of small and medium-scale livestock farmers. However, several factors can hinder successful animal production, as is the case for infectious diseases, such as the one caused by Corynebacterium pseudotuberculosis, known as caseous lymphadenitis (CLA). CLA has >90% prevalence in Brazilian herds and antibiotic treatment is not effective, consequently causing significant economic losses to farmers. Given the above, effective vaccines need to be developed to prevent this disease. This study aimed to evaluate the adjuvant activity of the lipid extract from the macroalgae Iridaea cordata as a candidate for developing an effective vaccine formulation. For such, four groups of six sheep each were inoculated with sterile 0.9% saline solution (G1), rCP01850 (G2), rCP01850 + I. cordata (G3), and rCP01850 + saponin (G4). Each sheep received two vaccine doses 30 days apart. Total IgG production levels significantly increased in experimental groups G3 and G4 on days 30, 60, and 90. On day 90, G3 showed higher total IgG production (p < 0.05) when compared to G4. When analyzing cytokine production, G3 was the only experimental group with significantly increased IFN-γ, IL-12, TNF-α, and IL-10 mRNA expression levels. Our results show the vaccine formulation containing rCP01850 adjuvanted with the I. cordata lipid extract elicited a Th1 immune response in sheep, indicating I. cordata lipid extract may be a promising adjuvant for developing an effective vaccine against infection caused by C. pseudotuberculosis.
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Adyuvantes Inmunológicos , Vacunas Bacterianas , Corynebacterium pseudotuberculosis , Enfermedades de las Ovejas , Células TH1 , Animales , Ovinos , Enfermedades de las Ovejas/prevención & control , Enfermedades de las Ovejas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Células TH1/inmunología , Corynebacterium pseudotuberculosis/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Citocinas/metabolismo , Citocinas/inmunología , Inmunoglobulina G/sangre , Infecciones por Corynebacterium/prevención & control , Infecciones por Corynebacterium/inmunología , Lípidos/inmunología , Brasil , Proteínas Bacterianas/inmunologíaRESUMEN
Mycoplasma (M.) hyopneumoniae is a primary etiological agent of porcine enzootic pneumonia (PEP), a disease that causes significant economic losses to pig farming worldwide. Current commercial M. hyopneumoniae vaccines induce partial protection, decline in preventing transmission of this pathogen or inducing complete immunity, evidencing the need for improving vaccines against PEP. In our study, we aimed to test the effectiveness of the SBA-15 ordered mesoporous silica nanostructured particles as an immune adjuvant of a vaccine composed of M. hyopneumoniae strain 232 proteins encapsulated in SBA-15 and administered by intramuscular route in piglets to evaluate the immune responses and immune-protection against challenge. Forty-eight 24-day-old M. hyopneumoniae-free piglets were divided into four experimental groups with different protocols, encompassing a commercial vaccine against M. hyopneumoniae, SBA-15 vaccine, SBA-15 adjuvant without antigens and a non-immunized group. All piglets were challenged with the virulent strain 232 of M. hyopneumoniae. Piglets that received the SBA-15 and commercial vaccine presented marked immune responses characterized by anti-M. hyopneumoniae IgA and IgG antibodies in serum, anti-M. hyopneumoniae IgA antibodies in nasal mucosa and showed an upregulation of IL-17 and IL-4 cytokines and downregulation of IFN-γ in lungs 35 days post-infection. Piglets immunized with SBA-15 vaccine presented a reduction of bacterial shedding compared to piglets immunized with a commercial bacterin. In addition, piglets from SBA-15 adjuvant suspension group presented increased IL-17 gene expression in the lungs without involvement of Th1 and Th2 responses after challenge. These results indicated that SBA-15 vaccine induced both humoral and cell-mediated responses in the upper respiratory tract and lungs, first site of replication and provided protection against M. hyopneumoniae infection with a homologous strain with reduction of lung lesions and bacterial shedding. Finally, these results enhance the potential use of new technologies such as nanostructured particles applied in vaccines for the pig farming industry.
Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Vacunas Bacterianas , Mycoplasma hyopneumoniae , Nanoestructuras , Neumonía Porcina por Mycoplasma , Dióxido de Silicio , Vacunas de Productos Inactivados , Animales , Mycoplasma hyopneumoniae/inmunología , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/inmunología , Neumonía Porcina por Mycoplasma/prevención & control , Neumonía Porcina por Mycoplasma/inmunología , Porcinos , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Anticuerpos Antibacterianos/sangre , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Derrame de Bacterias , Citocinas/inmunología , Pulmón/inmunología , Pulmón/microbiología , Inyecciones IntramuscularesRESUMEN
Lawsonia intracellularis is the causative agent of ileitis in swine that manifests as slower weight gain, mild or hemorrhagic diarrhea and/or death in severe cases. As an economically important swine pathogen, development of effective vaccines is important to the swine industry. In developing a subunit vaccine with three recombinant antigens - FliC, GroEL and YopN - we wanted to identify a formulation that would produce robust immune responses that reduce disease parameters associated with Lawsonia intracellularis infection. We formulated these three antigens with four adjuvants: Montanide ISA 660 VG, Montanide Gel 02 PR, Montanide IMS 1313 VG NST, and Montanide ISA 61 VG in an immunogenicity study. Groups vaccinated with formulations including Montanide ISA 660 VG or Montanide ISA 61 VG had significantly more robust immune responses than groups vaccinated with formulations including Montanide Gel 02 PR or Montanide IMS 1313 VG NST. In the challenge study, animals vaccinated with these antigens and Montanide ISA 61 VG had reduced lesion scores, reduced lesion lengths, and increased average daily gain, but no reduction in shedding relative to the control animals. This work shows that this vaccine formulation should be considered for future study in a field and performance trial.
Asunto(s)
Infecciones por Desulfovibrionaceae , Lawsonia (Bacteria) , Enfermedades de los Porcinos , Vacunas de Subunidad , Animales , Porcinos , Lawsonia (Bacteria)/inmunología , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/microbiología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Infecciones por Desulfovibrionaceae/prevención & control , Infecciones por Desulfovibrionaceae/inmunología , Infecciones por Desulfovibrionaceae/veterinaria , Vacunación/métodos , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Emulsiones , Derrame de BacteriasRESUMEN
BACKGROUND: This field efficacy study was designed to determine the efficacy of a new bivalent vaccine containing porcine circovirus type 2d (PCV2d) and Mycoplasma hyopneumoniae at three independent pig farms. METHODS: Three pig farms were selected based on their history of subclinical PCV2 infection and enzootic pneumonia. Each farm housed a total of 40, 18-day-old pigs that were randomly allocated to 1 of 2 treatment groups. Pigs were administered a 2.0 mL dose of the bivalent vaccine intramuscularly at 21 days of age in accordance with the manufacturer's recommendations, whereas unvaccinated pigs were administered a single dose of phosphate-buffered saline at the same age. RESULTS: Clinically, the average daily weight gain of vaccinated groups was significantly higher (p < 0.05) than those of unvaccinated animals during the growing (70-112 days of age), finishing (112-175 days of age) and overall (3-175 days of age) stages of production. Vaccinated animals elicited neutralizing anti-PCV2 antibodies and PCV2d-specific interferon-γ secreting cells (IFN-γ-SC), which reduced the amount of PCV2d genomic copies in blood and reduced lymphoid lesions severity when compared with unvaccinated animals. Similarly, vaccinated animals elicited M. hyopneumoniae-specific IFN-γ-SC, which reduced the amount of M. hyopneumoniae in the larynx and reduced lung lesions severity. CONCLUSIONS: The result of the field trial demonstrated that the bivalent vaccine was efficacious in the protection of swine herds suffering from subclinical PCV2d infection and enzootic pneumonia.
Asunto(s)
Vacunas Bacterianas , Infecciones por Circoviridae , Circovirus , Mycoplasma hyopneumoniae , Neumonía Porcina por Mycoplasma , Vacunas Virales , Animales , Circovirus/inmunología , Mycoplasma hyopneumoniae/inmunología , Infecciones por Circoviridae/veterinaria , Infecciones por Circoviridae/prevención & control , Porcinos , Neumonía Porcina por Mycoplasma/prevención & control , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Combinadas/inmunología , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/microbiología , Distribución Aleatoria , Sus scrofa , Infecciones AsintomáticasRESUMEN
BACKGROUND: The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. METHODS: In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18 years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30 days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. FINDINGS: We screened 2802 patients and enrolled 233 participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28 years (IQR 22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. INTERPRETATION: Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. FUNDING: US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.
Asunto(s)
Epidemiología Molecular , Sífilis , Treponema pallidum , Secuenciación Completa del Genoma , Humanos , Treponema pallidum/genética , Treponema pallidum/inmunología , Masculino , Femenino , Sífilis/epidemiología , Sífilis/microbiología , Adulto , Estudios Transversales , Genoma Bacteriano , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Persona de Mediana Edad , Adulto Joven , Variación Genética/genética , Filogenia , Estados Unidos/epidemiología , Genómica , TreponemaRESUMEN
The development and growth of fish farming are hindered by viral and bacterial infectious diseases, which necessitate effective disease control measures. Furunculosis, primarily caused by Aeromonas salmonicida, stands out as a significant bacterial disease affecting salmonid fish farms, particularly rainbow trout. Vaccination has emerged as a crucial tool in combating this disease. The objective of this experiment was to assess and compare the efficacy and duration of different vaccine protocols against furunculosis in large trout under controlled rearing conditions, utilizing single and booster administrations via intraperitoneal, oral, and immersion routes. Among the various vaccination protocols tested, only those involving intraperitoneal injection, administered at least once, proved truly effective in preventing the expression of clinical signs of furunculosis and reducing mortality rates. A single intraperitoneal administration provided protection for up to 2352°-days, equivalent to approximately 5 months in water at 16 °C. However, intraperitoneal vaccination may lead to reduced growth in the fish due to resultant intraperitoneal adhesions. Additionally, protocols incorporating booster doses via intraperitoneal injection demonstrated efficacy regardless of the administration route of the primary vaccination. Nevertheless, the use of booster vaccinations via the intraperitoneal route did not confer any significant advantage over a single intraperitoneal injection in terms of efficacy.
Asunto(s)
Aeromonas salmonicida , Enfermedades de los Peces , Forunculosis , Infecciones por Bacterias Gramnegativas , Oncorhynchus mykiss , Animales , Oncorhynchus mykiss/inmunología , Forunculosis/prevención & control , Forunculosis/inmunología , Aeromonas salmonicida/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/inmunología , Inyecciones Intraperitoneales/veterinaria , Autovacunas/administración & dosificación , Autovacunas/inmunología , Vacunación/veterinaria , Administración Oral , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunologíaAsunto(s)
Gonorrea , Neisseria gonorrhoeae , Humanos , Gonorrea/prevención & control , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/inmunología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/uso terapéutico , Masculino , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunologíaRESUMEN
A Coxiella burnetii vaccination program, targeting only doelings, was introduced on a German goat farm to curb bacterial shedding. In 2018, adults were vaccinated with a C. burnetii Phase I vaccine at three-weeks apart following pathogen diagnosis, with a booster administered six months later due to sustained high shedding. From 2018 to 2021, doelings received two vaccine doses without any further boosters. To assess the program's efficacy, vaginal swabs from up to 40 animals per age group were collected during kidding seasons from 2019 to 2022. Bulk tank milk (BTM) samples were gathered monthly from January 2018 to October 2022 to monitor herd-level shedding. Real-time PCR analysis determined genome equivalents in all three sample types. Serum samples were taken before the initial immunization and during the post-kidding season from up to 40 goats per age group annually from 2018 to 2022. Phase-specific ELISAs determined IgG Phase I and Phase II antibodies. Additionally, two serum samples per age group from 2022 were analyzed using a neutralization assay. A few goats continued shedding small quantities during subsequent kidding seasons. Although positive BTM samples decreased, they displayed an undulating trend. Most age groups exhibited robust IgG Phase I responses and lower IgG Phase II levels post immunization. Mean IgG levels remained elevated until the study ended compared to pre-vaccination levels in most age groups. Additionally, neutralizing antibodies were present regardless of IgG response. Overall, double vaccination induced lasting antibody levels, but did not entirely prevent C. burnetii shedding. The resilience of the observed humoral immune activity requires further investigation.
Asunto(s)
Anticuerpos Antibacterianos , Derrame de Bacterias , Vacunas Bacterianas , Coxiella burnetii , Enfermedades de las Cabras , Cabras , Fiebre Q , Vacunación , Animales , Coxiella burnetii/inmunología , Fiebre Q/prevención & control , Fiebre Q/inmunología , Fiebre Q/veterinaria , Enfermedades de las Cabras/prevención & control , Enfermedades de las Cabras/microbiología , Enfermedades de las Cabras/inmunología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunación/métodos , Vacunación/veterinaria , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Femenino , Leche/inmunología , Leche/microbiología , Inmunoglobulina G/sangre , Industria Lechera , AlemaniaRESUMEN
Staphylococcus aureus, Escherichia coli and Mycoplasma bovis are the most commonly isolated mastitis pathogens. The aim of this study was to evaluate the efficacy of a new mixed vaccine against mastitis caused by Staphylococcus aureus, Escherichia coli, and Mycoplasma bovis. For this purpose, a mixed inactivated vaccine was administered subcutaneously to 24 heifers as one dose (2 mL) on the 45th day before birth and the second dose 21 days later. In 9 heifers, 2 mL of PBS was administered as placebo instead of vaccine. Then, heifers were divided into 3 groups as 7 vaccinated and 3 unvaccinated animals. Staphylococcus aureus, Escherichia coli, and Mycoplasma bovis were administered to the groups through intramammary route. Three vaccinated heifers were considered the common control without bacteria in all groups. The parameters considered to assess the effect of vaccination were clinical findings, bacterial count in milk, somatic cell count, and antibody titers. Clinical signs were observed only in the unvaccinated placebo group. Bacteria count and somatic cell count in milk increased in vaccinated and unvaccinated heifers. However, this increase was less in vaccinated animals and gradually returned to the normal level. In the unvaccinated heifers, it was ever high. Serum antibody titers were measured before and after vaccination. Antibody titers were high in vaccinated heifers after vaccination and were negative in unvaccinated heifers. In conclusion, the mixed vaccine had beneficial effect against Staphylococcus aureus, Escherichia coli, and Mycoplasma bovis mastitis and stimulated the immune response of vaccinated heifers.