Oral vaccination of piglets against Mycoplasma hyopneumoniae using silica SBA-15 as an adjuvant effectively reduced consolidation lung lesions at slaughter

Mycoplasma (M.) hyopneumoniae is the main pathogen of porcine enzootic pneumonia (PEP). Its controlling is challenging, and requires alternative strategies. This study aimed to develop an oral vaccine against M. hyopneumoniae using a nanostructured mesoporous silica (SBA-15) as an adjuvant, and compare its effect with an intramuscular (IM) commercial vaccine (CV). Fifty 24 day-old M. hyopneumoniae-free piglets composed five equal groups for different immunization protocols, consisting of a CV and/or oral immunization (OI). Control piglets did not receive any form of immunization. All piglets were challenged with M. hyopneumoniae strain 232 on D49 by tracheal route. IgA antibody response in the respiratory tract, bacterial shedding and serum IgG were evaluated. The piglets were euthanized on 28 (D77) and 56 (D105) days post-infection. Lung lesions were macroscopically evaluated; lung fragments and bronchoalveolar fluid (BALF) were collected for estimation of bacterial loads by qPCR and/or histopathology examination. All immunization protocols induced reduction on Mycoplasma-like macroscopic lung lesions. IgA Ab responses anti-M. hyopneumoniae, the expression of IL-4 cytokine and a lower expression of IL-8 were induced by CV and OI vaccines, while IgG was induced only by CV. Oral immunization using silica as a carrier-adjuvant can be viable in controlling M. hyopneumoniae infection.

Immunogenicity of a new enhanced tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine against Bordetella pertussis in a murine model

Background The necessity of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine in adolescence and adults has been emphasized since the resurgence of small-scale pertussis in Korea and worldwide due to the waning effect of the vaccine and variant pathogenic stains in the late 1990s. GreenCross Pharma (GC Pharma), a Korean company, developed the Tdap vaccine GC3111 in 2010. Recently, they enhanced the vaccine, GC3111, produced previously in 2010 to reinforce the antibody response against filamentous hemagglutinin (FHA). In this study, immunogenicity and efficacy of the enhanced Tdap vaccine compared and evaluated with two Tdap vaccines, GC3111 vaccine produced in 2010 previously and commercially available Tdap vaccine in a murine model. Methods Two tests groups and positive control group of Balb/c mice were primed with two doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine followed by a single booster Tdap vaccine at 9 week using the commercially available Tdap vaccine or 2 Tdap vaccines from GC Pharma (GC3111, enhanced GC3111). Humoral response was assessed 1 week before and 2 and 4 weeks after Tdap booster vaccination. The enhanced GC3111 generated similar humoral response compare to the commercial vaccine for filamentous hemagglutinin (FHA). The interferon gamma (IFN-γ) (Th1), interleukin 5 (IL-5) (Th2) and interleukin 17 (IL-17) (Th17) cytokines were assessed 4 weeks after booster vaccination by stimulation with three simulators: heat inactivated Bordetella pertussis (hBp), vaccine antigens, and hBp mixed with antigens (hBp + antigen). A bacterial challenge test was performed 4 weeks after booster vaccination. Results Regarding cell-mediated immunity, cytokine secretion differed among the three simulators. However, no difference was found between two test groups and positive control group. All the vaccinated groups indicated a Th1 or Th1/Th2 response. On Day 5 post-bacterial challenge, B. pertussis colonies were absent in the lungs in two test groups and positive control group. Conclusions Our results confirmed the immunogenicity of GC Pharma’s Tdap vaccine; enhanced GC3111 was equivalent to the presently used commercial vaccine in terms of humoral response as well as cell-mediated cytokine expression.

Effect of Bivalent Vaccines against Vibrio anguillarum and Aeromonas salmonicida subspecie achromogenes on Health and Survival of Turbot

The efficacy of intraperitoneal injection of an oil-based bivalent autogenous vaccine and the commercial vaccine AlphaJect 3000 (Pharmaq AS) to prevent atypical furunculosis and vibriosis in turbot was analyzed. The effect of both vaccines on health parameters and survival of fish after challenge with V. anguillarum and A. salmonicida subsp. achromogenes was tested. The autogenous vaccine conferred high levels of protection and long-lasting immunity against both pathogens with a single dose. However, severe side effects were observed in turbot injected with this autovaccine and minor negative effects with the AlphaJect 3000 vaccine and the adjuvant Montanide or Eolane. All vaccinated fish showed remarkable antibody agglutination titers, higher than those of control fish, which were maintained 160 d after vaccination. In conclusion, the autogenous bivalent vaccine induces long-lasting protection against atypical furunculosis and vibriosis in turbot, after administration of a single dose, at the cost of high side effects in fish. Therefore, the development of new vaccines should focus on autovaccines and the use of liquid paraffin adjuvants that increase protection with reduced or no side effects.

Efficacy of Two Chlamydia abortus Subcellular Vaccines in a Pregnant Ewe Challenge Model for Ovine Enzootic Abortion

Chlamydia abortus, the aetiological agent of enzootic abortion of ewes, is a major cause of reproductive loss in small ruminants worldwide, accounting for significant economic losses to the farming industry. Disease can be managed through the use of commercial inactivated or live whole organism-based vaccines, although both have limitations particularly in terms of efficacy, safety and disease-associated outbreaks. Here we report a comparison of two experimental vaccines (chlamydial outer membrane complex (COMC) and octyl glucoside (OG)-COMC) based on detergent extracted outer membrane preparations of C. abortus and delivered as prime-boost immunisations, with the commercial live vaccine Cevac® Chlamydia in a pregnant sheep challenge model. No abortions occurred in either experimental vaccine group, while a single abortion occurred in the commercial vaccine group. Bacterial shedding, as a measure of potential risk of transmission of infection to naïve animals, was lowest in the COMC vaccinated group, with reductions of 87.5%, 86.4% and 74% observed for the COMC, OG-COMC and live commercial vaccine groups, respectively, compared to the unvaccinated challenge control group. The results show that the COMC vaccine performed the best and is a safer efficacious alternative to the commercial vaccines. However, to improve commercial viability, future studies should optimise the antigen dose and number of inoculations required.

Immunological evaluation of inactivated Newcastle disease vaccine depending on adjuvant composition

Newcastle disease is a global problem that is being recorded in most countries and also a serious obstacle to exchange of genetic material of poultry in various countries of the world. Control of the Newcastle disease comprises correct injection of efficacious vaccines so as to decrease or eliminate the clinical disease. Our goal was to perform comparative studies of the vaccines against Newcastle disease of water in oil type, the adjuvant being mineral oil mixed with emulsifiers (Span-80 and Tween-80) and ready-to-use adjuvant system (Montanide ISA 70), and study the impact of composition of adjuvant constituent on physical-chemical and immunogenic properties of inactivated vaccines. To reproduce virus-containing material and carried out titration of the viruses, we used chicken embryos free of pathogenic microflora. Aqueous phase for the preparation of emulsion-based vaccines of water in oil type consisted of antigen to Newcastle disease of La-Sota strain, manufactured by Biotestlab Ltd, and phosphate-saline buffer. To evaluate the effectiveness of the vaccine and induce immune response, we used 1-day old pathogen-free chickens, which were obtained from chicken embryos free of pathogenic microflora. As the positive control in the experiment, we used commercial vaccine. One-day chickens were divided into 3 groups (I, II, III) comprising 12 individuals each and one group (IV) consisting of 8 individuals as the control group with individual numeration. Chickens in groups I, II and III were divided into two subgroups (n = 8 and n = 4) to determine immunogenic efficiency and safety of the vaccine. Immunization was carried out through single subcutaneous injections in the region of the neck. To study immunogenic efficiency, the chickens were immunized with the dose of 0.1 mL (1 dose), and 0.2 mL (2 doses) to determine safety. After the immunization of 1-day old pathogen-free chickens with 0.1 mL dose, the obtained level of antibodies in the serum of vaccinated chickens on days 14, 21, 28, 35 and 42 after the vaccination indicated the ability of provoking the immune response to Newcastle disease at high level and safety of the vaccination for chickens. All the recipes of the examined series of the vaccines and the commercial vaccine produced appropriate level of viscosity according to the criterion equaling ≤ 200 mm2/s at Р <0.05, promoting fluidity of the vaccine and providing easier passage through the needle during the application. Both of the studied vaccines may be used in poultry farming for prophylaxis of Newcastle disease among chickens.

Metallacarborane Derivatives Effective against Pseudomonas aeruginosa and Yersinia enterocolitica

Pseudomonas aeruginosa is an opportunistic human pathogen that has become a nosocomial health problem worldwide. The pathogen has multiple drug removal and virulence secretion systems, is resistant to many antibiotics, and there is no commercial vaccine against it. Yersinia pestis is a zoonotic pathogen that is on the Select Agents list. The bacterium is the deadliest pathogen known to humans and antibiotic-resistant strains are appearing naturally. There is no commercial vaccine against the pathogen, either. In the current work, novel compounds based on metallacarborane cage were studied on strains of Pseudomonas aeruginosa and a Yersinia pestis substitute, Yersinia enterocolitica. The representative compounds had IC50 values below 10 µM against Y. enterocolitica and values of 20–50 μM against P. aeruginosa. Artificial generation of compound-resistant Y. enterocolitica suggested a common mechanism for drug resistance, the first reported in the literature, and suggested N-linked metallacarboranes as impervious to cellular mechanisms of resistance generation. SEM analysis of the compound-resistant strains showed that the compounds had a predominantly bacteriostatic effect and blocked bacterial cell division in Y. enterocolitica. The compounds could be a starting point towards novel anti-Yersinia drugs and the strategy presented here proposes a mechanism to bypass any future drug resistance in bacteria.

Salmonella Bacterin Vaccination Decreases Shedding and Colonization of Salmonella Typhimurium in Pigs

Since the occurrence of swine salmonellosis has increased over time and control strategies other than biosecurity are highly recommended, the present study aimed to evaluate the efficacy of vaccination with Salmonella Choleraesuis and Salmonella Typhimurium bacterins in pigs. Two experimental groups were formed: G1, animals immunized with two doses of a commercial vaccine (n = 20); G2, control group (n = 20). After vaccination, all pigs were orally challenged (D0) with 108 CFU of Salmonella Typhimurium and evaluated for 40 days. Every 10 days after D0, five piglets from each experimental group were euthanized and submitted to the necroscopic examination, when organ samples were collected. Blood samples and rectal swabs were collected before the first dose of the vaccine (D−42), before the second dose (D−21), before the challenge (D0), and thereafter, every three days until D39. Blood count, serum IgG measurement by ELISA, and the excretion of Salmonella Typhimurium in feces were evaluated. While the results from blood count and serum IgG concentration did not differ, the detection and excretion of Salmonella between G1 and G2 differed (p < 0.05). Therefore, it was observed that this vaccine partially protected the animals against experimental infection with Salmonella Typhimurium, reducing the excretion of bacteria in feces.

Vaccine advertising: preach to the converted or to the unaware?

Encouraging people to vaccinate is a challenging endeavor, but one which has tremendous public health benefits. Doing so requires overcoming barriers of awareness, availability, and (sometimes) vaccine hesitancy. Here we focus on nudging people to vaccinate through online advertising. We conducted a pre-registered online ads campaign encouraging people to vaccinate against three diseases: influenza, human papillomavirus, and herpes zoster. Ads were shown to ~69,000 people and were compared to similar ads shown to 8.6 million people. Outcome measures were clicks on ads and future searches for relevant terms. We find that ads have two main effects: First, a congruence effect whereby ads increase the likelihood of clicks and future searches by up to 116% in people who express an interest in the disease or the vaccine. Most commercial vaccine advertising is aimed entirely at this population. Second, we observed a priming effect, where ads shown to people who were searching for terms unrelated to the vaccine could be encouraged to click on them (odds ratios of 7.5–33.0) and, more often, search for the vaccine later (hazard ratios of 6.9–157.3). We provide analysis for optimizing vaccine advertising campaign budgets to balance the two populations. These findings demonstrate that digital advertising campaigns should consider not just advertising to direct keywords or to individuals that look exactly like existing customers, but consider tangential keywords that draw a wider target population who are likely earlier in their conversion funnel, thus increasing the number of people who vaccinate and maximizing vaccines uptake.

THE EFFECTS OF IBD FIBROGUM-BOVAC VACCINE AND A COMMERCIAL VACCINE ON THE BODY WEIGHT BURSAL WEIGHT AND DEVELOPMENT OF ANTIBODIES IN BROILERS

A CHICKEN embryo-fibroblast (CEF) cell culture-adapted infectious bursal disease vaccine (Fibrogumbovac) and a commercial vaccine were studied for their effects on the rate of growth, bursal atrophy and the attainment of antibody level in 450 broilers. No appreciable difference in weight was observed in vaccinated birds when compared with unvaccinated control birds. The birds were vaccinated at the age of 4 week and at 9 week of age the average weights for birds vaccinated with IBD Fibrogum-bovac, the commercial vaccine and unvaccinated controls were respectively 1.949, 2.014 and 1,900kg. The vaccinated birds did not gain weight as rapidly as the controls between the 9th and 14th week (Table 1). The relative weight loss per week for the last five weeks (10th to 14th week) averaged 0.7 per cent for the IBD Fibrogumbovac vaccinated birds as compared with control birds. The highest antibody levels recorded in vaccinated birds at the end of two weeks were 1:1024 for Fibrogumbovac, and 1:16 for the commercial vaccine. On the third day after vaccination when the bursa of Fabricius was expected to be largest the average weight of the buçsa of 5 birds was found to be 0.250, 0.135 and 0.245 per cent of body weight respectively for birds vaccinated with IBD Fibrogun-bovac vaccine, the commercial vaccine, and unvaccinated controls.