Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage

Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd.

Bacille Calmette-Guérin/DNAhsp65 prime-boost is protective against diabetes in non-obese diabetic mice but not in the streptozotocin model of type 1 diabetes

Type I diabetes is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this study was to evaluate the prophylactic potential of a prime-boost strategy involving bacille Calmette-Guérin (BCG) and the pVAXhsp65 vaccine (BCG/DNAhsp65) in diabetes induced by streptozotocin (STZ) in C57BL/6 mice and also in spontaneous type 1 diabetes in non-obese diabetic (NOD) mice. BCG/DNAhsp65 vaccination in NOD mice determined weight gain, protection against hyperglycaemia, decreased islet inflammation, higher levels of cytokine production by the spleen and a reduced number of regulatory T cells in the spleen compared with non-immunized NOD mice. In the STZ model, however, there was no significant difference in the clinical parameters. Although this vaccination strategy did not protect mice in the STZ model, it was very effective in NOD mice. This is the first report demonstrating that a prime-boost strategy could be explored as an immunomodulatory procedure in autoimmune diseases. © 2013 British Society for Immunology.

An approach to local immunotoxicity induced by adjuvanted vaccines

The occurrence of injection site reactions following immunization is the most frequently reported toxicity manifestation of vaccines; however, the different types of local reactions and the different mechanisms involved are still unclear. Here, the current advances in adjuvants and the role that adjuvants play in local reactions are reviewed. The role of adjuvants in the formation of the loco-regional complex (LRC), which consists of the injection site, draining lymphatic vessels and regional lymph nodes, is also discussed. Finally, strategies and recommendations for the rational design of adjuvanted vaccines are discussed, with a particular interest in the reduction of local inflammation. © 2013 Elsevier B.V.

Effect of vaccination and the immunomodulators bacillus of Calmette-Guerin, Avridine and Propionibacterium acnes on rabies in mice

Responses: of vaccination and treatment to immunomodulators against rabies in mice were evaluated through macrophage inhibition factor (MIF), intra-pad inoculation (IPI) and serum neutralization (SN) tests and by the detection of gamma-interferon (IFN-gamma). Onco-BCG, Avridine and Propionibacterium acnes were administered to groups of mice. Higher survival rates were found in animals treated with P. acnes. Lower levels of IFN-gamma were observed in the groups of infected and vaccinated mice. The IPI was not effective on detecting the response of delayed-type hypersensitivity. Vaccine induced in the infected animals a more intense response to MIF reaction. (C) 1998 Elsevier B.V. Ltd. All rights reserved.

Effect of the bacillus of Calmette-Guerin, Propionibacterium acnes and avridine as immunomodulators in antirabies vaccination of mice using the Fuenzalida-Palacios mouse brain vaccine

Using the laboratory mice, Fuenzalida-Palacios mouse brain human rabies vaccine was administered in groups of animals previously inoculated with rabies virus and then submitted to treatments with the immunomodulators onco-BCG, avridine and Plopionibacterium acnes. Humoral and cellular immune responses were evaluated through the macrophage inhibition factor (MIF), intra-pad inoculation (IPI) and serum neutralization (SN) tests and by the detection of gamma-interferon (IFN-gamma). The IPI test was not effective in detecting the response of delayed-type hypersensitivity, contrary to MIF, which showed the immune cellular response. Higher levels of IFN-gamma were observed in the groups of mice vaccinated and treated with avridine and P. acnes. Although immunomodulating activities have been detected, the use of adjuvants with the Fuenzalida-Palacios type vaccine in mice did not reveal any encouraging results. (C) 1999 Elsevier B.V. Ltd. All rights reserved.

Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis

The FML antigen of Leishmania donovani, in combination with either Riedel de Haen (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis (VL). Significant and specific increases in anti-FML IgG and IgM responses were detected for all adjuvants, and in anti-FML IgG1, IgG2a and IgG2b and delayed type of hypersensitivity to L. donovani lysate (DTH), only for all saponins and IL12. The QS21-FML and QuilA-FML groups achieved the highest IgG2a response. QuilA-FML developed the strongest DTH and QS21-FML animals showed the highest serum IFN-gamma concentrations. The reduction of parasitic load in the liver in response to each FML-vaccine formulation was: 52% (P < 0.025) for BCG-FML, 73% (P < 0.005) for R-FML, 93% (P < 0.005) for QuilA-FML and 79.2% (P < 0.025) for QS21-FML treated animals, respectively. Protection was specific for R-FML and QS21-FML while the QuilA saponin treatment itself induced 69% of LDU reduction. The FML-saponin vaccines promote significant, specific and strong protective effects against murine visceral leishmaniasis. BCG-FML induced minor and non-specific protection while IL 12-FML, although enhancing the specific antibody and IDR response, failed to reduce the parasitic load of infected animals. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Newcastle disease in white Pekin ducks: response to experimental vaccination and challenge

A total of 120 Pekin ducks were distributed at random into four experimental groups, vaccinated or not against Newcastle disease (ND): G1 (Ulster 2C strain), G2 (B1 strain), G3 (LaSota strain), and G4 (nonvaccinated group). At 60 days of age, all groups were challenged with a pathogenic ND virus (NDV) suspension, and a group of specific pathogen free (SPF) chicks (G5) was also inoculated. Cloacal and tracheal swabs from all birds were collected after six, 14, 20, and 30 days post-challenge for virus isolation. NDV was isolated in 100% of SPF chicks. Pekin ducks from all groups, vaccinated or not, did not show any ND clinical signs, demonstrating that these birds are not susceptible to ND clinical disease. In the control group (G4), the virus was isolated 20 to 30 days after challenge, suggesting their possible NDV carrier state. In the vaccinated groups, no virus was isolated. This demonstrates that vaccination of white Pekin ducks against NDV is important to reduce NDV shedding in the field.

Efficacy of several Salmonella vaccination programs against experimental challenge with Salmonella gallinarum in commercial brown layer and broiler breeder hens

The protective effect of various Salmonella vaccines regimens against an experimental Salmonella Gallinarum challenge (SGNalr strain at 12 wk of age) was evaluated in two experiments. In Experiment 1 commercial brown layers were vaccinated according to one of the following programs: (i) two doses of a SE bacterin (Layermune SE; group 1); (ii) a first dose of a live SG9R vaccine (Cevac SG9R) followed by a SE bacterin (Layermune SE; group 2); (iii) one dose of each of two different multivalent inactivated vaccines containing SE cells (Corymune 4 & Corymune 7; group 3) or (iv) not vaccinated (group 4). In Experiment 2, broiler breeders were given the same vaccination treatments except for the group vaccinated with the multivalent vaccines. Overall, in both experiments, all vaccination schemes were effective in reducing mortality after challenge with a SG field strain. Primary vaccination with an initial dose of a live SG9R vaccine followed some weeks later by a dose of an inactivated SE bacterin was the most effective (p<0.05) vaccination program against mortality induced by field SG experimental challenge in both experiments. In conclusion, Salmonella vaccination programs containing SE bacterins alone or in combination with a live SG9R vaccine are effective in preventing mortality induced by infection of field SG. Nevertheless, it is important to emphasize that any vaccination program against any Salmonella serotype will only be effective if it is part of a sound and comprehensive biosecurity program designed for Salmonella control in poultry farms.

Inflammatory responses of Nile tilapia Oreochromis niloticus to Streptococcus agalactiae: effects of vaccination and yeast diet supplement

This study evaluated the effects of dietary supplementation with 0.3% Saccharomyces cerevisiae yeast cell wall and of vaccination against Streptococcus agalactiae on the cellular component of acute inflammation induced in the coelomic cavity of Nile tilapia Oreochromis niloticus and on survival of the fish after challenge. A total of 84 tilapia of mean (+/- SD) weight 125.0 +/- 1.5 g were distributed among twelve 310 l fiberglass tanks according to a 2 x 2 x 3 factorial design in the following manner: with and without supplementation; 2 stimulations (oily solution without S. agalactiae vaccine and vaccination); 15 d later all fish were intracoelomically challenged with 10(8) CFU ml(-1) of a homologous strain of S. agalactiae, and evaluated after 6, 24 and 48 h, with 7 replicates. The fish received the non-supplemented or supplemented diet for a total of 77 d. The vaccination was performed on the 60th day, intracoelomically, as a single injection of 0.5 ml of the vaccine containing 10(8) CFU ml(-1). Fifteen days later, all the fish were challenged with S. agalactiae by means of an intracoelomic inoculation of 10(8) CFU ml(-1). No mortality was observed among the supplemented fish. The fish that were fed the non-supplemented diet and immunized with the bacterium presented a mortality rate of 28.5%. Among the non-supplemented and non-immunized fish, the mortality rate was 38.09%. Supplementation, in both vaccinated and non-vaccinated fish, induced larger accumulations of thrombocytes, lymphocytes and macrophages at the inflammatory focus. The results suggest that supplementation with 0.3% yeast cell wall, in both vaccinated and non-vaccinated fish, improved the inflammatory response of the fish and protected against the challenge. Vaccination increased the defense response, but the effect was stronger when associated with supplementation with S. cerevisiae.

Efficacy of several vaccination programmes in commercial layer and broiler breeder hens against experimental challenge with Salmonella enterica serovar Enteritidis

Two experiments were performed to evaluate the protective effect of various vaccination combinations given at 5 and 9 weeks of age against experimental challenge with Salmonella enterica serovar Enteritidis ( SE) phage type 4 at 12 weeks of age. In Experiment 1, groups of commercial layers were vaccinated by one of the following programmes: Group 1, two doses of a SE bacterin (Layermune SE); Group 2, one dose of a live Salmonella enterica serovar Gallinarum vaccine (Cevac SG9R) followed by one dose of the SE bacterin; Group 3, one dose of each of two different multivalent inactivated vaccines containing SE cells (Corymune 4K and Corymune 7K; and Group 4, unvaccinated, challenged controls. In Experiment 2, groups of broiler breeders were vaccinated by the same programmes as Groups 1 and 2 above while Group 3 was an unvaccinated, challenged control group. All vaccination programmes and the challenge induced significant (P<0.05) seroconversion as measured by enzyme-linked immunosorbent assay. Overall, in both experiments, all vaccination schemes were significantly effective in reducing organ (spleen, liver and caeca) colonization by the challenge strain as well as reducing faecal excretion for at least 3 weeks. Vaccinated layers in Groups 1 and 2 and broiler breeders in Group 2 showed the greatest reduction in organ colonization and the least faecal excretion. In Experiment 1, layers vaccinated with multivalent inactivated vaccines containing a SE component (Group 3) were only moderately protected, indicating that such a vaccination programme may be useful in farms with good husbandry and housing conditions and low environmental infectious pressure by Salmonella.

Predictors of adherence to influenza vaccination for healthcare workers from a teaching hospital: a study in the prepandemic era

Introduction: Even before the 2009 pandemics, influenza in healthcare workers (HCW) was a known threat to patient safety, while Influenza vaccine coverage in the same group was generally low. Identification of predictors for HCW adherence to Influenza vaccination has challenged infection control committees. Methods: Our group conducted a cross-sectional survey in December 2007, interviewing 125 HCWs from a teaching hospital to identify adherence predictors for Influenza vaccination. The outcomes of interest were: A - adherence to the 2007 vaccination campaign; B - adherence to at least three yearly campaigns in the past five years. Demographic and professional data were assessed through univariate and multivariate analysis. Results: of the HCWs interviewed, 43.2% were vaccinated against Influenza in 2007. However, only 34.3% of HCWs working in healthcare for more than five years had adhered to at least three of the last five vaccination campaigns. Multivariate analysis showed that working in a pediatric unit (OR = 7.35, 95% I = 1.90-28.44, p = 0.004) and number of years in the job (OR = 1.32, 95%CI = 1.00-1.74, p = 0.049) were significant predictors of adherence to the 2007 campaign. Physicians returned the worst outcome performances in A (OR = 0.40, 95%CI = 0.16-0.97, p = 0.04) and B (OR = 0.17, 95%CI = 0.05-0.60, p = 0.006). Conclusions: Strategies to improve adherence to Influenza vaccination should focus on physicians and newly-recruited HCWs. New studies are required to assess the impact of the recent Influenza A pandemics on HCW-directed immunization policies.

Evaluation of Experimental Vaccination Against Newcastle Disease in Lovebirds (Agapornis roseicollis): Investigation of the State of Virus Carrier.

The aim of this study was to evaluate the importance of vaccination against Newcastle Disease (ND) in lovebirds (Agapornis roseicollis) and to investigate the state of carrier of the virus (NDV) in this species. There were used 48 lovebirds, distributed at random into 4 experimental groups: GI (Ulster 2C strain), Gil (B1 strain), Gill (LaSota strain) and GIV (non-vaccinated group). At 12 months of age, all groups were challenged with a pathogenic virus (NDV) suspension (ElD50 = 1081510.1 mL) and a group of Specific-Pathogen-Free (SPF) chicks were used as control of the virus. Cloaca) swabs from each bird were collected after 9, 14 and 21 days post-challenge for detection of genome viral excretion by Reverse Transcription Polymerase Chain Reaction RT-PCR. Lovebirds of GI, Gil and Gill did not demonstrate any signs of ND. They were refractory to the clinical disease. In lovebirds from the control group, NDV genome was detected 9 and 21 days after challenge. Therefore it was demonstrated the state of carrier of NDV by lovebirds. In birds from the vaccinated groups, genome viral excretion was not detected by RT-PCR. It was also demonstrated the importance of the vaccination in the suppression of the state of virus carrier of ND in lovebirds.

Antibody response to newcastle disease vaccination in a flock of young partridges (Rhynchotus rufescens)

Ten young partridges (Rhynchotus rufescens) were vaccinated with the lentogenic strain of Newcastle disease virus. Another eight unvaccinated birds were kept in close contact with the treated flock. Antibodies levels were measured over the course of 3 mo in all birds using the hemagglutination inhibition (HI) test and the liquid-phase blocking enzyme-linked immunosorbent assay (LPB-ELISA). The LPB-ELISA was standardized, and the results were compared with those obtained with the HI test. Antibodies increased after 23 days postvaccination in 16 birds with no side effects as determined by both the HI test and the LPB-ELISA.

Vaccination protocol and bacterial strain affect the serological response of beef calves against blackleg

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