Effectiveness Of Oral Vaccination Research Articles

Attenuated Streptococcus agalactiae WC1535 ∆Sia perturbs the gut microbiota of Oreochromis niloticus, massively colonizes the intestine, and induces intestinal mucosal immunity after intraperitoneal inoculation.

We previously developed and assessed the effectiveness of the attenuated Streptococcus agalactiae (Group B Streptococcus, GBS) strain WC1535 ∆Sia (with neuA-D gene cluster deletion) vaccine in tilapia (Oreochromis niloticus). In this study, we characterized the bacterial communities of the tilapia intestines by 16S rRNA high-throughput sequencing and assessed the serum antibody response, expression of immune-related genes, and histological changes following formalin-killed GBS vaccine (FKV) and the live attenuated vaccine ∆Sia (LAV). Results showed that FKV and LAV induced robust systemic and intestinal mucosal immune responses in tilapia without causing obvious pathological changes in the hindgut, spleen, and head kidney but exerted different effects on intestinal bacterial communities. The richness or diversity of the intestinal bacterial community of FKV tilapia showed no significant changes compared with that of the control fish (p > 0.05) at either day 21 post-initial vaccination (21 dpiv) or day 35 (day 14 after the second immunization) (35 dpiv). The community composition of FKV tilapia and controls was significantly similar, although the relative abundance of some genera was significantly altered. Relative to control fish, the gut ecosystem of LAV tilapia was significantly disturbed with a substantial increase in community diversity at 21 dpiv (p < 0.05) and a significant decrease at 35 dpiv in fish with high serum antibody response (ΔSia35H) (p < 0.05). However, there was no significant difference between ΔSia35H and ΔSia35L (low serum antibody response) fish (p > 0.05). Moreover, the community composition of LAV tilapia at 21 dpiv or 35 dpiv was considerably different from that of the controls. Particularly, GBS ∆Sia was found to be abundant in the intestine at 21 and 35 dpiv. This result suggested that the parenteral administration of the LAV (∆Sia) may also have the effect of oral vaccination in addition to the immune effect of injection vaccination. In addition, a significant correlation was found between the expression of immune-related genes and certain bacterial species in the intestinal mucosal flora. Our findings will contribute to a better understanding of the effects of inactivated and attenuated vaccines on gut microbiota and their relationship with the immune response.

Type II NKT Cell Agonist, Sulfatide, Is an Effective Adjuvant for Oral Heat-Killed Cholera Vaccines.

Oral vaccination has the potential to offer a safer and more efficacious approach for protection against enteric pathogens than injection-based approaches, especially in developing countries. One key advantage is the potential to induce intestinal immune responses in addition to systemic immunity. In general, antigen delivery via the oral route triggers weak immune responses or immunological tolerance. The effectiveness of oral vaccination can be improved by co-administering adjuvants. However, a major challenge is the absence of potent and safe oral adjuvants for clinical application. Here, the Type II NKT cell activator sulfatide is shown for the first time to be an effective oral adjuvant for Vibrio cholerae vaccine antigens in a mouse model. Specifically, administration of sulfatide with the oral cholera vaccine Dukoral® resulted in enhancement of intestinal antigen-specific IgA in addition to Th1 and Th17 immune responses. In summary, sulfatide is a promising adjuvant for inclusion in an oral cholera vaccine and our data further support the potential of adjuvants targeting NKT cells in new vaccine strategies.

Effectivity of oral recombinant DNA vaccine against Streptococcus agalactiae in Nile tilapia

The effects of oral vaccination by two immune routes (gavage and mixed fodder administration) using a recombinant DNA vaccine SL7207-pVAX1-sip against Streptococcus agalactiae were assessed. SL7207-pVAX1-sip significantly enhanced various innate immune responses of tilapia, such as total serum protein, superoxide dismutase activity, lysozyme activity, complement C3 concentration in serum, serum antibacterial activity, and interleukin 1β and tumor necrosis factor-α. Vaccinated fish had higher relative percent survival values (57% and 63% for gavage group and mix fodder administration, respectively) at 10 weeks after S. agalactiae infection. When administered mixed fodder, the DNA vaccine SL7207-pVAX1-sip against S. agalactiae may produce more effective protection. These findings can promote the application and development of DNA vaccines in aquaculture.

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles).

The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or to know whether oral vaccination of wild badgers with BCG will significantly reduce transmission of the disease.

Does the infection with endoparasites influence the effect of oral vaccination against classical swine fever in wild boar?

Classical swine fever is a highly contagious viral disease that affects domestic and wild suids and could cause important economic losses. It is the most dangerous infectious disease of the wild boar that can cause severe death in densely populated areas. The aim of the study was to determine the effect of endoparasites on the oral vaccination against classical swine fever in wild boar. The study compared classical swine fever antibody titres in wild boar treated and untreated with antiparasitics. Fourteen six-month-old wild boar piglets were tested via direct ELISA to detect specific antibodies in blood serum after vaccination. Before the vaccination, one group of piglets was administered antiparasitic therapy; the other group of animals remained untreated. Twenty-eight days post vaccination, piglets from the first group (free of parasites) showed significantly (P = 0.0015) higher concentrations of specific antibodies than the infected animals. Obtained results proved that parasitic infections substantially influence the efficacy of oral vaccination against classical swine fever and may support the ability of the virus to produce infectious diseases and its transmission in the wild boar population. For that reason, antiparasitic therapy of wild boar populations before their vaccination is highly recommended in order to increase the vaccine’s efficacy.

Oral immunization with whole yeast producing viral capsid antigen provokes a stronger humoral immune response than purified viral capsid antigen

Weak antibody responses to protein antigens after oral immunization remain a serious problem. Yeasts have a rigid cell wall and are inherently resistant to harsh conditions, suggesting that recombinant antigens made in yeast could have a greater chance of making contact with the immune cells of the gastrointestinal (GI) tract in intact form. We compared antibody responses to oral immunization with purified recombinant antigen, used in the conventional manner, and responses to whole recombinant yeast producing the antigen intracellularly. Recombinant capsid protein (CP) of red-spotted grouper necrosis virus (RGNNV) was used as model antigen and Saccharomyces cerevisiae as host. The purified CP was obtained from the S.cerevisiae producing the RGNNV CP. Whole recombinant yeast producing RGNNV CP provoked 9-27 times higher anti-RGNNV CP IgG titres than purified RGNNV CP. Moreover, sera from mice immunized with the recombinant yeast had neutralizing activity against RGNNV, while those from mice immunized with purified CP did not. These results show that whole recombinant yeast is a promising platform for antigen delivery by oral immunization. Provoking sufficient antibody responses by oral immunization has been an enormous challenge because of the harsh conditions of the gastrointestinal (GI) tract. Immunization strategies using purified antigen to make oral vaccines are incapable of commercialization because excessive amount of antigen is required to provoke antibody responses. Therefore, resolving the problems concerning the cost and effectiveness of oral vaccines is a high priority. Our results suggest that recombinant yeast has great potential for inducing antigen-specific immune responses by oral immunization. We believe that oral immunization using recombinant yeast can be a breakthrough technology.

Rabies - epizootiological situation at the territory of Serbia and countries in the region from 2006. to 2012.

Rabies is a disease that occurs both in animals and people, with relatively long period of incubation, intense clinical course and fatal ending. Majority of cases of illnes and death in people are caused by the standard rabies virus. According to books of regulations on suppression and eradiction of rabies from 1988. and 2009., each suspected rabies has to be laboratory confirmed. From 2006. to 2012. within the passive surveilance, 3549 samples of brain tissue were examined for the presence of rabies virus. The virus was confirmed in 923 samples by using the method of direct imunofluorescence. From 2006. to 2012. there were diagnosed 192, 160, 233, 181, 104, 43 and 10 positive cases, respectively. For the purpose of rabies eradiction at the territory of the Republic of Serbia, a regional project of oral vaccination of foxes against rabies has been implemented since 2010.Within monitoring of the effectiveness of oral vaccination against rabies which was carried out at the end of 2011. and at the beginning of 2012., there were examined 1385 samples, out of which 11 reacted positively. The virus was dominantly present in the fox population. During 2008. and 2009., a relatively large number of rabid cats was registered, what indicates a transmission of rabies from the fox to the cat population. The incidence of rabies at the territory of Serbia significantly differs from one epizootic area to another. Northern parts of the country (Sombor and Subotica epizootic regions) have more favorable situation with only two cases of rabies for the last 7 years. In the period until 2010., in Pozarevac, Novi Sad, Jagodina, Pancevo, Belgrade and Nis epizootic region, a gradual decline in number of positive cases was noticed. International project for oral vaccination of foxes against rabies which has been implemented at the territory of the Republic of Serbia and neighboring countries, influenced a significant reduction of registered rabies cases.

Efficacy of oral vaccination against swine erysipelas in growing-finishing pigs in a clinically infected Slovakian pig herd

In a large Slovakian growing-finishing pig production unit, the effects of oral vaccination against swine erysipelas (SE) were investigated in three groups of pigs of 10 weeks of age. In group 1, the pigs were vaccinated intramuscularly at 1 and 3 weeks after arrival in the growing-finishing barn using an Erysipelothrix rhusiopathiae bacterin. Group 2 pigs were vaccinated at the same time as group 1 using an oral avirulent live SE vaccine administered through drinking water; the pigs in the third group were placebo treated. Clinical signs of acute SE, arthritic changes, average daily weight gain (ADG), feed conversion ratio, and mortality were evaluated. None of the pigs in groups 1 and 2 but 31.7% of the control animals (group 3) showed typical clinical signs of acute SE. More ( P < 0.01) non-vaccinated pigs had chronic arthritic changes compared with groups 1 and 2. No significant differences in mortality were recorded between the groups. Groups 1 and 2 had higher ( P < 0.05) ADG and lower feed conversion ratios compared with group 3 pigs. The results demonstrated that the oral avirulent live culture was efficacious in significantly reducing the clinical symptoms caused by E. rhusiopathiae infection, so enhancing the pigs’ performance.

Effects of oral vaccination and immunomodulation by cholera toxin on experimental Helicobacter pylori infection, reinfection, and gastritis.

Therapeutic vaccination is an attractive strategy to control infection and disease caused by Helicobacter pylori. In mice infected with H. pylori we have studied the protective effect of oral immunization with an H. pylori lysate preparation given together with the mucosal adjuvant cholera toxin (CT), both against the initial infection and against a later reinfection challenge. We have also examined the effects of treatment with the CT adjuvant alone on H. pylori infection and reinfection. Specific immunization with lysate was found to result in a sixfold reduction of the extent (bacterial load) of the primary infection and also to provide similar levels of protection against reinfection. However, these effects were associated with severe postimmunization gastritis. In contrast, oral treatment with CT alone at the time of initial infection, while unable to suppress the initial infection, gave rise to a 20-fold reduction in bacterial load upon reinfection without causing any associated gastric inflammation. Both the infected animals that were specifically immunized and those that were treated with CT only displayed increased in vitro proliferative responses of mononuclear cells to H. pylori antigens. Antibody levels in response to H. pylori were on the other hand only marginally increased after treatment with CT, whereas they were markedly elevated after immunization with lysate plus CT, with a rise in both (Th2-driven) immunoglobulin G1 (IgG1) and, especially, (Th1-driven) IgG2a antibodies. The results illustrate the complex balance between protection and harmful inflammation after postinfection vaccination against H. pylori as studied in a mouse model.

Effects of oral vaccination against vibriosis in turbot, Scophthalmus maximus (L.), and sea bass, Dicentrarchus labrax (L.)

Abstract. Turbot, Scophthalmus maximus (L.), and sea bass, Dicentrarchus labrax (L.), are susceptible to vibriosis, a septicaemia caused in France by Vibrio anguillarum 408. A bacterin produced with this strain by Rhône–Merieux has been tested orally in both species and, as a comparison, by intraperitoneal injection. During a challenge carried out 4 weeks later by intraperitoneal inoculation, the protection observed in orally vaccinated fishes was significant (72 % in sea bass and 70 % in turbot). Eleven weeks after vaccination, this protection is still significant. The mean titre of serum agglutinins was weakly increased in orally vaccinated fishes. Bacteriostatic antibodies have also been searched for in serum, but compared to agglutination, the applied technique leads to lower titres and it has not been possible to prove the presence of such antibodies after oral vaccination. Passive immunizations using serum from orally vaccinated fishes (2 months after vaccination) confers some protection against a challenge carried out by inoculation of virulent vibrio. Therefore, the production of serum factors following oral vaccination of sea bass and turbot may be involved in generalized protection of fish.

The effect of oral immunization on the population of lymphocytes migrating to the mammary gland of the sow

Sows were immunized orally with live Escherichia coli according to various immunization schedules. Six pregnant gilts were used; 4 immunized at various intervals during the last month of gestation, 1 control immunized after parturition following suppression of lactation by weaning and 1 non-immunized control. The effect of oral vaccination on cell populations from lymphoid organs was studied. The in vitro proliferative responses of the cell populations to K88 antigen, anti-Ig sera and mitogens were used to demonstrate the distribution of sensitized lymphocytes over different lymphoid organs. The capacity of these cells to produce antigen-specific Ig was determined by in ovo translation of their mRNA. Oral administration of antigen resulted in the appearance of K88-positive cells in lymphoid organs. In lactating sows, sensitized cells preferentially occured in the mammary lymph nodes, whereas after suppression of lactation such a distribution was not seen. A possible route of migration of sensitized lymphocytes is discussed in relation to the local immune response. The antibody isotype produced by sensitized lymphocytes seemed to depend on the immunization schedule. The most effective schedule was one starting early in gestation and comprising frequent administration of antigen. This caused an optimal distribution of sensitized lymphocytes capable of IgA production.

Secretory IgA and direct killing of Shigella by serum components.

Shigellosis is an enteric infection in which bacteria are restricted to the intestinal lumen and mucosa, and deeper systemic invasion is rare, even in nonimmune individuals. Spontaneous recovery is common, and subsequent resistance to reinfection may occur, but field trials with parenteral vaccines have shown systemic antibodies to be nonprotective. However, the effectiveness of oral vaccines suggests that local or intestinal immunity may exist. Since previous studies have shown large quantities of secretory IgA to be present in Shigella diarrhea stools (1), it seems possible that local immunity may be mediated by this immunoglobulin. The following studies investigate direct serum killing as one possible mechanism through which secretory IgA could exert an anti-Shigella effect.

Canine copro-immunoglobulins.

Coproantibodies [1] in experimental cholera have been investigated to assess the effectiveness of oral vaccination [1-3], but the levels of intestinal antibody have been difficult to measure and to correlate with protective effects of the cholera vaccine. Recently, the canine species has been used as an animal model for experimental cholera because the syndrome of fluid and electrolyte loss can be produced [4]. Also, the lack of demonstrable gastrointestinal histopathology in this canine model [5] makes further analogy with the human illness possible. Since the dog is a useful experimental model and is subject to many of the diseases that occur in man, we have been interested in the canine immunological system, particularly in describing the immunoglobulins in serum [6, 7] and in external secretions [8, 9]. This paper will include a discussion of the immunoglobulin content of normal canine intestinal secretions and will quantitate the concentrations of these copro-immunoglobulins. An isolation procedure for recovery of the copro-immunoglobulins, particularly secretory IgA, will be outlined; in addition, some of the physical properties of the IgA molecule and its polypeptide-chain components will be examined.