Administration Of Oral Vaccine Research Articles

Investigation of 3-D ordered materials with a high adsorption capacity for BSA and their potential application as an oral vaccine adjuvant

3-D ordered macroporous (3DOM) materials were customized for BSA adsorption and further oral immunization. These carriers have a high adsorption capacity and our customized carrier showed a distinctive double-plateau adsorption behavior. Different BSA release rates (between the two plateaus) could be obtained by adjusting the ratio of the protein adsorbed on the internal surface and the external surface. This suggests that the release pattern was determined by the adsorption state. One benefit is that the same carrier could have different release profiles making it possible to study the relationship between the release behavior and adjuvant effects without any distractions. Compared with free BSA alone, a significantly higher level of serum IgG, IgA induced by BSA/3DOM was observed and the release profile had an effect on the immunity. The IgG1 and IgG2a titers suggesting that both the Th1 and Th2 mediated immune response were induced. Therefore, this research could help in the development of a novel inorganic oral adjuvant and provide a new avenue for the administration of oral vaccine.

Rotavirus oral vaccine administration errors are rare

Rotavirus oral vaccine administration errors are rare

Directional Activation of Intestinal Dendritic Cells by an Oral Targeted Multivalent Vaccine

Parenteral injectionis the most common routeof administration for vaccines and therapeutics. Despite their frequent use, needle-based immunizations have several limitations; (i) needle phobias that are common in both adults and children, (ii) the requirement of trained medical personnel to administer vaccines, creating a limitation for mass vaccination, and (iii) accidental needle sticks, a serious concern in both developed and developing countries. Possible alternatives to injections have recently emerged and include (i) dermal and (ii) oral administration of vaccines. Here, we describe a methodology developed in our laboratory using intestinal bacteria that are considered safe for human consumption. Additionally, we have designed a dendritic cell (DC)-targeting sequence that delivers antigens directly to DCs. In this report, we discuss how DC-targeting peptide binding is not limited to human and murine antigen presenting cells; rather, it consistently binds with DCs of different species. Our data suggest that a DC-targeted oral vaccine platform could be used to develop vaccines for a variety of host animals.

Adsoption of two vaccine-related proteins to montmorillonite and organo-montmorillonite

Adsorption of proteins to clay minerals is widely studied, mostly in agricultural issues, due to its importance in soil. The poultry industry experiences an increasing need for new generations of effective vaccines, requiring minimal handling of bird during administration. Among the problems of vaccination with genetically engineered vaccines is low immunogenicity. Therefore, the development of effective adjuvants for vaccination is a central task. In addition, oral administration of vaccines is more convenient and economic for the poultry industry. The modified heat-labile eteroxin (LT) protein was found to be a safe and immunogenic adjuvant, and showed the ability to enhance immune responses against an antigen co-administered with, for example—the viral protein 2 (VP2). As a model of a possible combination for an oral administrated vaccine, adsorption of VP2 and LT on SWy-2 montmorillonite and on an organo-montmorillonite (berberine adsorbed on SWy-2) were tested. Results of this multidisciplinary study, which combines methods used in clay mineral studies with biological assays, prove feasibility to attach two vaccine-related proteins to organoclay mineral particles, yielding close vicinity between the proteins that may lead to an immune response via the monosialoganglioside (GM1) receptor. Such complexes may be used as vaccine carriers to stimulate desired immune responses.

Alpha-galactosylceramide is an effective mucosal adjuvant for repeated intranasal or oral delivery of HIV peptide antigens

Mucosal delivery of vaccines against sexually transmitted pathogens is important to elicit strong immune responses at biologically relevant sites. However, inclusion of appropriate adjuvants is essential to overcome the inherent mucosal tolerance. We present evidence in support of the effectiveness of co-administering alpha-galactosylceramide (α-GalCer) as an adjuvant with a CTL-inducing HIV envelope peptide, via either oral or intranasal route, to prime antigen-specific immune responses in multiple systemic and mucosal compartments. Contrary to the known potential of repeated parenteral dosing with α-GalCer to induce NKT cell anergy that could compromise adoptive immunity development, we have observed that two and three doses delivered by the intranasal or oral route were more efficient in priming broader antigen-specific immune responses. These results demonstrate the effectiveness of α-GalCer as adjuvant for repeated intranasal or oral administration of vaccines for protection against mucosally transmitted pathogens.

Immunogenicity and tolerance following HIV-1/HBV plant-based oral vaccine administration

Transgenic tobacco plants expressing a HIV-1 polyepitope associated with hepatitis B (HBV) virus-like particles (VLPs) were previously described. It is demonstrated here that oral administration of these transgenic plants to humanized HSB mice to boost DNA-priming can elicit anti-HIV-1 specific CD8+ T cell activation detectable in mesenteric lymph nodes. Nevertheless, a significant regulatory T cell activation was induced in vivo by the vaccination protocols. The balance between tolerance and immunogenicity remains the main concern in the proof of concept of plant-based vaccine.

Possible Relationship between Systemic Side Effects and Sensitization to rPar j 2 in Allergic Patients Submitted to an Ultra-Rush (20 min) Sublingual Immunotherapy and Selected by Component Resolved Diagnosis

Background: The pollen of Parietaria spp., a weed of the Urticaceae family, is a major cause of respiratory allergy in the Mediterranean area, where the most common species are Parietaria judaica and Parietaria officinalis. In this study, we evaluated the specific serum IgE-binding profiles to individual P. judaica pollen recombinant major allergen, and Phleum pratense cytoskeletal profilin and a 2-EF-hand calcium-binding allergen homologous to cross-reactive Parietaria pollen allergens, in patients allergic to pollen with positive skin test towards Parietaria spp. extract. Methods: The present observation included 220 patients from the province of Cuneo, north-west Italy, all suffering from rhino-conjunctivitis and/or asthma selected on the basis of skin test positive to P. judaica extract. The sera were evaluated for specific IgE reactivity to P. judaica pollen major recombinant(r) allergen Par j 2, Phleum pratense pollen allergens rPhl p 7 (2-EF-hand calcium binding protein) and rPhl p 12 (profilin), both identified as cross-reactive Parietaria spp. allergens, using Pharmacia CAP System. Out of 220 patients, 37 patients with IgE reactivity to rPar j 2 and 105 patients sensitized to at least one timothy pollen major allergen (i. e. rPhl p 1, rPhl p 2, natural Phl p 4 and rPhl p 6) were submitted to an ultra-rush protocol of sublingual immunotherapy (SLIT). The occurrence of adverse reactions were evaluated in both groups. Results: All 220 patients with pollinosis and positive in vivo skin prick tests had in vitro positive CAP results to P. judaica natural extract. On the contrary, in these patients the prevalence of Par j 2-specific IgE was only 33.2% (73/220). In fact, 116/220 (52.7%) patients with serum specific IgE to crude Parietaria pollen extract had specific IgE to Phl p 12, 18/220 (8.1%) subjects with specific IgE to rPhl p 12 also exhibited specific IgE to Phl p 7 and 26/220 (11.8%) subjects had specific IgE against rPhl p 7. Particularly, geometric mean (25th–75th percentile) of specific IgE to rPar j 2 were as follows: 2.87 kUA/l (1.005–7.465). Out of 73 patients with specific IgE to rPar j 2, 7 subjects (9.6%) had also specific IgE to rPhl p 7, 12 (16.4%) had specific IgE to rPhl p 12 and 4 (4.1%) patients had specific IgE to both recombinant allergens. Of 37 patients under an ultra-rush protocol of SLIT, 3 subjects (8.1%) experienced generalized urticaria, and 1 of them also had diarrhea 3 h after the last dose of Parietaria judaica extract oral-vaccine administration. On the contrary, no systemic reactions were observed in 105 patients after Phleum pratense extract oral intake after a similar ultra-rush SLIT protocol (p = 0.0046). Conclusions: In the light of present findings, allergen extract-based diagnosis, in vivo and in vitro, cannot discriminate allergic patients that are genuinely sensitized to Parietaria spp. major allergens or to other major allergens to which current immunotherapeutic allergy extracts are standardized. Therefore, in vitro component resolved diagnosis is the unique tool to define the disease eliciting molecule(s). Finally, during sublingual immunotherapy, not only the dose of allergen, but also the biochemical characteristic of the major allergen administered may be an important factor in determining possible systemic reactions.

EFEKTIVITAS VAKSIN POLIVALEN UNTUK PENGENDALIAN VIBRIOSIS PADA KERAPU TIKUS (Cromileptes altivelis)

The objective of this research was to know the effectiveness of polyvalen Vibrio vaccine to control vibriosis in humpback grouper (Cromileptes altivelis). The effectiveness of vaccine was evaluated by the survival rate (SR), relative percent survival (RPS), mean time to death (MTD) as well as growth rate of vaccinated fish. This research consisted of 4 treatments (control, injection, immersion, and oral vaccinations) in quadruplicates. Injection vaccination was conducted by intraperitoneal injection of polyvalen vaccine at 107 cells/fish. Immersion vaccination was done by immersing the fishes at 107 cells/ml for 30 minutes. Oral administration of vaccine was also carried out at 107 cells/fish. One week after the first vaccination, second vaccination (booster) was carried out at the same dosage and by the same administration. One week after the second vaccination, fishes were challenged with 3.16x104 cells/fish of Vibrio ordalii 3J by intraperitoneal injection, and reared for 20 days post infection. Results indicated that polyvalen Vibrio vaccine increased SR (P<0.01) up to 100%. Vaccination was also able to delay MTD of fishes. However, the vaccination was not influence the growth rate of fish.

Gastrointestinal transit time of nondisintegrating radio-opaque pellets in suckling and recently weaned piglets

The objective was to determine the gastrointestinal (GI) transit times of pellets in piglets at different time points around weaning, as transit times are essential criteria to develop oral drug delivery systems. Nondisintegrating radio-opaque pellets were given orally in order to define the transit times by radiography. The radiographs were analysed with a software programme to calculate the number of pellets present in the different parts of the GI tract. In suckling piglets, the gastric emptying was faster (75% in 1.5 to 3.5 h), and the colonic accumulation (to 73%) was greater than in weaned piglets (3 days, 2 and 3 weeks postweaning, 65% gastric emptying in 18 h, 75% in 17 h, and 75% in 7 h, respectively; maximal colonic accumulations of 48%). Immediately after weaning, the transit was markedly prolonged but shortened with increased postweaning time (3 days, 2 and 3 weeks postweaning, 85% excretion in 175.5, 77, and 50.5 h, respectively). Three weeks postweaning, the transit was no longer affected by weaning as transit times were similar to values reported in growing and adult pigs, and retention appeared to be restricted to the stomach and the colon. These data are of crucial importance in the design of enteric-coated formulations for oral administration of vaccines and therapeutics to young piglets and for human research using the pig model.

Probiotics in the third millennium

Probiotics are “living microorganisms which upon ingestion in certain numbers exert health benefits beyond inherent general nutrition”. Since 1987, when the first publication on the properties of the Lactobacillus GG was done, overall, there have been over 200 publications in peer-reviewed scientific journals. This paper will report the status and the prospectus of probiotics research at the beginning of the Third Millennium. Probiotics have proven benefits in treatment and prevention of rotavirus diarrhoea in children and reduction of antibiotic-associated intestinal side-effects. Interesting results have recently been published regarding food allergies and atopic eczema in children. Prevention of vaginitis and of travellers' diarrhoea have also been reported. Promising results are being reported in patients with inflammatory bowel disease, cystic fibrosis, dental caries and irritable bowel syndrome. It has also been suggested that probiotics could enhance oral vaccine administration, and that they may help treatment against Helicobacter pylori infection, but further studies are needed. Future areas of research regard probiotics' role in the process of carcinogenesis, given their influence on the gut microflora, and as immune modulators in autoimmune disorders. The possibility of introducing appropriate genes to the probiotics to make them produce various compounds is also under investigation. However, there is still confusion in the minds of the authorities over whether a probiotic is a drug, a food, or a dietary supplement. The challenge is to continue research to define the appropriate uses of probiotics and discover new applications which will bring benefit to humankind.

PLG microparticles stabilised using enteric coating polymers as oral vaccine delivery systems

Novel poly(dl-lactide-co-glycolide) microparticles for oral vaccine delivery were formulated using the enteric polymers Eudragit ® L100-55 and carboxymethylethylcellulose (CMEC) as stabilisers. To serve as a control, microparticles were also produced using the conventional PVA surfactant. In all three cases the antigen, ovalbumin (OVA)-loaded microparticles produced were less than 5 μm in diameter and had a spherical, smooth rounded appearance. The presence of surfactants at the microparticle surface was demonstrated by the surface analysis techniques, XPS and SSIMS. Incubation of microparticles with solutions of pepsin or trypsin led to the removal of a proportion of the antigen associated with all three systems. However, in three CMEC-stabilised microparticle formulations and one of three Eudragit formulations, a high percentage of the associated antigen was protected from removal by a solution of pepsin at pH 1.2 compared with the PVA-stabilised microparticles. In addition, with certain CMEC and Eudragit formulations a degree of protection was also afforded to the associated OVA against removal by trypsin at pH 7.4. Following the incubation of microparticles in simulated gastric fluid a higher percentage of intact antigenic OVA was detected in microparticles stabilised using CMEC than in the PVA - and Eudragit - stabilised formulations. Oral immunisation of mice with OVA-loaded microparticles stabilised using either of the three surfactants led to the induction of specific serum IgG and salivary IgA antibodies. Significantly higher levels of specific salivary IgA antibody to OVA were measured in mice immunised with the CMEC-stabilised microparticles than with the other two formulations. This novel approach in PLG microparticle formulation may have potential in increasing the efficacy of microparticulate systems for the oral administration of vaccines.

Polymer-grafted starch microparticles for oral and nasal immunization.

Microparticle delivery systems for oral vaccine administration are receiving considerable attention. A novel silicone polymer-grafted starch microparticle system was developed that is efficacious both orally and intranasally. Unlike most other microparticle systems, this novel system does not appear to retard the release of antigen or to protect antigen from degradation. The results indicate that a unique physiochemical relationship occurs between protein antigen and silicone in a starch matrix that facilitates the mucosal immunogenicity of antigen. This leads to predominance of Th2 antibody response. Taken together, these findings indicate that this novel microparticle system may be advantageous for the delivery of small quantities of antigen, especially intranasally, and may be useful for the induction of oral tolerance.

Altenative Routes of Measles Immunization: a Review

Measles is one of the major causes of childhood mortality in developing countries, despite current prevention of over 2 million child deaths each year by measles vaccination programmes. New strategies, such as mass campaigns, and possibly new preparations of measles vaccines, may facilitate further progress in controlling the disease and improving the prospects for its ultimate eradication. To evaluate the potential for non-percutaneous routes of vaccine administration to improve control, we reviewed studies of serological responses to measles vaccine after intradermal, conjunctival, oral, aerosol and intranasal administration.The response to intradermal vaccination exceeded percutaneous results in only one of eight instances in five studies where such comparisons could be made, often producing substantially lower seroresponses. Further, intradermal administration using a needle and syringe is more difficult than subcutaneous vaccination. After oral administration of vaccine, less than 50% of children seroconverted in three small studies. Intranasal administration has not yet been studied extensively, but it may be susceptible to interference by upper respiratory infections. Seroconversion after conjunctival administration was very variable, and this route was difficult practically in young children.In infants below 9 months of age, aerosol administration of vaccine resulted in 80% or better seroresponse in seven of nine trials, with the Edmonston–Zagreb strain in standard titre doses consistently producing better results than the Schwarz strain. However, seroresponses after subcutaneous administration clearly exceeded those from aerosols of the same vaccine in four of six comparisons. Several trials noted practical difficulties in aerosol administration in young infants. In contrast, older seronegative children generally responded well to aerosol administration of vaccine (above 90% and often 100% seroresponse), regardless of vaccine strain and often with surprisingly low estimated retained doses. In each of three studies where it was possible to compare the same vaccines given percutaneously and by aerosol to seropositive children, better seroresponses followed aerosols. In older children, aerosols of the Edmonston–Zagreb strain also rather consistently provided better seroresponses than aerosols of the Schwarz strain, with the most notable differences in seropositive children. Thus, with the possible exception of very young infants, the aerosol route is promising and offers several theoretical and practical advantages as well.Further randomized trials should be conducted to evaluate comparative responses to aerosolized, intranasal, and subcutaneous vaccine, especially in those age ranges targeted for mass campaigns (most commonly 9 months to 15 years). The development of improved technology for aerosol delivery of measles vaccine would greatly advance the potential for wide scale use of this route, especially in mass campaigns in low income countries.

Oral vaccination with alginate microsphere systems

Oral vaccination is a simple, efficient way of inducing immunity at mucosal surfaces. The slow development of oral vaccines has been mainly due to the lack of suitable delivery systems. We have used hydrogel microspheres to deliver various vaccines to several animal species by oral administration. Oral delivery of vaccines using alginate microspheres elicited the production of secretory IgA (sIgA) at the mucosal surfaces in mice, rabbits, and cattle. Oral vaccination of chicken resulted in an increased delayed-type hypersensitivity, a cell-mediated immune response, indicating a positive response to the vaccine. Our studies have clearly shown that alginate microspheres are effective for the oral administration of vaccines.

Enteric immunization of mice against influenza with recombinant vaccinia.

Intrajejunal administration to mice of a recombinant vaccinia virus containing the influenza virus hemagglutinin gene induced IgA antibody in nasal, gut, and vaginal secretions. It also induced IgG antibody in serum and cell-mediated immunity. The immunization provided significant protection against an influenza virus challenge. This work suggests that enteric-coated recombinant vaccinia could be an orally administered, inexpensive, multivalent, temperature-stable, safe, and effective vaccine for children that could be particularly useful in developing nations, where multiple injections are not easily administered. Oral administration of vaccines should also reduce children's fear of shots at the doctor's office.

Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine

The efficacy of a rhesus rotavirus vaccine (MMU 18006, serotype 3) against infantile diarrhea was evaluated by active home surveillance of a group of 320 children 1-10 months of age in Caracas, Venezuela. During a 1 year period following oral administration of vaccine or placebo under a double-masked code, over 600 diarrheal episodes were detected. Etiologic studies revealed that heat-stable toxin (ST) producing enterotoxigenic E. coli (ETEC) was the most common diarrheal agent detected (34%) followed by enteropathogenic E. coli (EPEC, 10.9%), heat-labile toxin (LT) producing ETEC (7.6%), rotavirus (6.9%), Cryptosporidium (4.8%) and Campylobacter (1.3%). ST-producing ETEC were also recovered from over 20% of control stool specimens obtained during diarrhea-free periods, whereas EPEC, rotavirus, Cryptosporidium, and Campylobacter were rarely detected in such control specimens. Rotavirus was responsible for about one-half of the more severe cases of diarrhea. Twenty-two of 151 infants who received placebo (14.6%) and eight of 151 receiving a 10(4) PFU dose of vaccine (5.3%) had rotavirus diarrhea during the follow-up period for an efficacy level of 64% against any rotavirus diarrhea. However, vaccine efficacy reached 90% against the more severe cases of rotavirus diarrhea and was noticeably high in the 1-4 month age group. Serotypic analysis of the rotaviruses detected suggests that the resistance induced by the vaccine was type specific since significant protection was only evident against serotype 3 rotaviruses. A 10(3) PFU dose tested initially in 18 children did not appear to protect against rotavirus diarrhea.

Vaccination route, infectivity and thioglycollate broth administration: effects on live vaccine efficacy of auxotrophic derivatives of Salmonella choleraesuis

An aromatic-dependent, therefore non-virulent, derivative of a mouse-virulent strain of Salmonella choleraesuis previously shown not to be effective as a live vaccine when given intraperitoneally (i.p.) to lty s mice, was administered to BALB/c mice. Two doses given i.p. or by feeding did not protect against i.p. or oral challenge with 50 to 5000 LD 60 of the virulent ancestor strain. By contrast two doses given intravenously (i.v.) gave almost complete protection against i.p. or oral challenge with 500 LD 50 and some protection against larger doses. The number of live bacteria (cfu) in the liver and spleen 24 h after administration of the live vaccine was less than 1% of the number inoculated i.p., but c. 25% of the number injected i.v. The number of cfu in the gut 24 h after oral vaccine administration was only c. 10 −5 of the number fed. Administration of thioglycollate broth i.p. 5 days before i.p. vaccination increased recovery of live vaccine cfu in the liver and spleen and its protective efficacy. In each case the live vaccine did not multiply extensively in vivo. We have previously shown that a purine- and a thymine-requiring derivative of S. choleraesuis were each considerably attenuated but unlike the aro derivative were effective as i.p. live vaccines in mice. Doses of these strains ( c. 10 4 cfu) found protective were administered i.p. to BALB/c mice. Each strain multiplied extensively in the liver and spleen to c. 10 7 cfu by day 6. All these results are in agreement with a correlation of protective efficacy of a live vaccine with the persistence of a large number of the vaccine bacteria in the liver and spleen for several days.

Alteration in oligonucleotide fingerprint patterns of the viral genome in poliovirus type 2 isolated from paralytic patients.

A close relationship was demonstrated by oligonucleotide fingerprinting between genomes of the poliovirus type 2 Sabin vaccine strain and recent isolates from paralytic cases associated with vaccination in Japan. The oligonucleotide maps of isolates from an agammaglobulinemic patient, who continued to excrete poliovirus type 2 for 3.5 years after the administration of oral vaccine, showed that the genomic alteration proceeded gradually, retaining the majority of the oligonucleotides characteristic of the vaccine strain for a long period, indicating vaccine origin for the isolates. The final isolate at month 41, however, lost the majority of these oligonucleotides. The heterologous antigenic relationship between the final isolate and the previous isolates was also observed. The serial alteration in electrophoretic mobility of the major structural proteins (VP1, VP2, and VP3) was observed throughout the excreting period. These results indicate that the population of the virus in this individual changed markedly during the last short period (about 3 months), in which the treatment with secretory immunoglobulin A was carried out. Genome comparisons in oligonucleotide maps show that some oligonucleotides in the genome of the vaccine strain are highly mutable after passage in humans.

Genetic marker studies of poliovirus. II. Strains isolated from cases of poliomyelitis associated with the administration of live attenuated vaccine.

Strains of poliovirus were obtained from 13 of the 18 persons in England and Wales with paralytic episodes after administration of oral vaccine in 1962. They have been studied using three marker tests: the R.C.T.40 test, intratypic serodifferentiation and inhibition by dextran sulphate. For comparison a number of strains from subjects with non-paralytic vaccine-associated reactions and from patients with paralytic poliomyelitis not related to vaccine were also tested.Of the eight patients excreting type 1 strains seven came from South Wales where an outbreak was in progress. They all resemble naturally occurring strains from the outbreak in growing at 39·3° but not at 39·8° C.Only one subject excreted type 2 virus which was of vaccine type.The type 3 strains included a series from a family group where a range of results from vaccine to the wild range was obtained. Three other patients with vaccineassociated paralysis excreted type 3 strains with the characteristic of naturally occurring strains.

Live Poliovirus Vaccines

A five-day conference dealing with the status of live poliovirus vaccines was held under the auspices of the World Health Organization and the Pan American Sanitary Bureau in June, 1959. Although the conference was organized because of pressures on the sponsoring agencies to provide advice on the use of live polio vaccines, the objective of the meeting was not to make recommendations but to marshal pertinent data and to elicit differences of opinion in order to define areas requiring further investigation. The participation of the proponents of the three different sets of live virus strains, of individuals responsible for field trials that already have involved administration of oral vaccine to some millions of people, and of a distinguished group of virologists, epidemiologists, and public health administrators provides an interesting 692-page conference record that summarizes the knowledge of live poliovirus vaccines as of mid-year 1959.