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Anthrax vaccines  [cached]
Splino Miroslav,Patocka Jiri,Prymula Roman,Chlibek Roman
Annals of Saudi Medicine , 2005,
Abstract: SUMMARY : Anthrax, an uncommon disease in humans, is caused by a large bacterium, Bacillus anthracis. The risk of inhalation infection is the main indication for anthrax vaccination. Pre-exposure vaccination is provided by an acellular vaccine (anthrax vaccine adsorbed or AVA), which contains anthrax toxin elements and results in protective immunity after 3 to 6 doses. Anthrax vaccine precipitated (AVP) is administered at primovaccination in 3 doses with a booster dose after 6 months. To evoke and maintain protective immunity, it is necessary to administer a booster dose once at 12 months. In Russia, live spore vaccine (STI) has been used in a two-dose schedule. Current anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever). Serious adverse reactions occur in about 1% of vaccinations. New second-generation vaccines in current research programs include recombinant live vaccines and recombinant sub-unit vaccines.
Comparative Immunological Response of Commercial Oil Based and Liposomal Vaccines of Avian Influenza H7  [PDF]
Khalid Farooq,Abdul Hameed,Tariq Javed,Ikram Ullah
Pakistan Journal of Biological Sciences , 2006,
Abstract: Avian Influenza (AI) has been recognized as a highly contagious and lethal generalized viral disease of birds. In this study, immune response of layers to the commercial oil based and liposomal vaccines of avian influenza H7 was evaluated. Thirty commercial layers were divided into three groups, T1, T2 and T3 with 10 birds in each group. Group T1 served as control, Group T2 was immunized with conventional AI oil-based vaccines, 0.5 mL/bird and Group T3 was immunized with AI Liposomal vaccines 0.5 mL/bird through sub/cut injection. Blood samples were taken and sera were separated at day 0, 7, 14, 21, 28 and day 35. Each time at least 6 samples were taken for antibody titration through AGPT. The geometric mean titre (GMT) of birds in T1, T2 and T3 was 4 ±1.02 at day 0. No significant difference was observed in the titres at day 0 in all the groups. The GMT (Geometric Mean Titer) of control group was 4 ±1.02 at day 7, 6.79 ±1.02 at day 14 and 8 ±1.02 from day 21 to 35. The antibody titre increased slowly from 32 on day 7 to 630.3 on day 35 in birds vaccinated with oil based vaccine, whereas a somewhat quick increase in immune response from 64 on day 7 to 891.4 on day 35 was observed in birds vaccinated with liposomal vaccine. The results showed that immune response of layers in term of GMT was well established with AI liposomal vaccine as compared to that of oil based vaccine. The present study will be helpful in preventing the commercial losses of the farmers and preventing the flock mortality due to the high efficacy of liposomal vaccine against avian influenza.
Induction of a Protective Response in Mice by the Dengue Virus NS3 Protein Using DNA Vaccines  [PDF]
Simone M. Costa, Anna Paula Yorio, Ant?nio J. S. Gon?alves, Mariana M. Vidale, Emmerson C. B. Costa, Ronaldo Mohana-Borges, Marcia A. Motta, Marcos S. Freire, Ada M. B. Alves
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025685
Abstract: The dengue non-structural 3 (NS3) is a multifunctional protein, containing a serino-protease domain, located at the N-terminal portion, and helicase, NTPase and RTPase domains present in the C-terminal region. This protein is considered the main target for CD4+ and CD8+ T cell responses during dengue infection, which may be involved in protection. However, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus. In the present work, we investigate the protective efficacy of DNA vaccines based on the NS3 protein from DENV2. Different recombinant plasmids were constructed, encoding either the full-length NS3 protein or only its functional domains (protease and helicase), fused or not to a signal peptide (t-PA). The recombinant proteins were successfully expressed in transfected BHK-21 cells, and only plasmids encoding the t-PA signal sequence mediated protein secretion. Balb/c mice were immunized with the different DNA vaccines and challenged with a lethal dose of DENV2. Most animals immunized with plasmids encoding the full-length NS3 or the helicase domain survived challenge, regardless of the presence of the t-PA. However, some mice presented clinical signs of infection with high morbidity (hind leg paralysis and hunched posture), mainly in animal groups immunized with the DNA vaccines based on the helicase domain. On the other hand, inoculation with plasmids encoding the protease domain did not induce any protection, since mortality and morbidity rates in these mouse groups were similar to those detected in the control animals. The cellular immune response was analyzed by ELISPOT with a specific-CD8+ T cell NS3 peptide. Results revealed that the DNA vaccines based on the full-length protein induced the production of INF-γ, thus suggesting the involvement of this branch of the immune system in the protection.
Immunological response in mice bearing LM3 breast tumor undergoing Pulchellin treatment  [cached]
de Matos Djamile,de Ribeiro Lívia Carolina,Tansini Aline,Ferreira Lucas
BMC Complementary and Alternative Medicine , 2012, DOI: 10.1186/1472-6882-12-107
Abstract: Background Ribosome-inactivating proteins (RIP) have been studied in the search for toxins that could be used as immunotoxins for cancer treatment. Pulchellin, a type 2 RIP, is suggested to induce immune responses that have a role in controlling cancer. Methods The percentage of dendritic cells and CD4+ and CD8+ T cells in the spleen (flow cytometry), cytokines’ release by PECs and splenocytes (ELISA) and nitric oxide production by PECs (Griess assay) were determined from tumor-bearing mice injected intratumorally with 0.1 ml of pulchellin at 0.75 μg/kg of body weight. Statistical analysis was performed by one-way ANOVA with Tukey’s post hoc test. Results Pulchellin-treated mice showed significant immune system activation, characterized by increased release of IFN-γ and Th2 cytokines (IL-4 and IL-10), while IL-6 and TGF-β levels were decreased. There was also an increase in macrophage’s activation, as denoted by the higher percentage of macrophages expressing adhesion and costimulatory molecules (CD54 and CD80, respectively). Conclusions Our results suggest that pulchellin is promising as an adjuvant in breast cancer treatment.
Induction of Neutralizing Antibody Response against Four Dengue Viruses in Mice by Intramuscular Electroporation of Tetravalent DNA Vaccines  [PDF]
Eakachai Prompetchara, Chutitorn Ketloy, Poonsook Keelapang, Nopporn Sittisombut, Kiat Ruxrungtham
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092643
Abstract: DNA vaccine against dengue is an interesting strategy for a prime/boost approach. This study evaluated neutralizing antibody (NAb) induction of a dengue tetravalent DNA (TDNA) vaccine candidate administered by intramuscular-electroporation (IM-EP) and the benefit of homologous TDNA boosting in mice. Consensus humanized pre-membrane (prM) and envelope (E) of each serotypes, based on isolates from year 1962–2003, were separately cloned into a pCMVkan expression vector. ICR mice, five-six per group were immunized for three times (2-week interval) with TDNA at 100 μg (group I; 25 μg/monovalent) or 10 μg (group II; 2.5 μg/monovalent). In group I, mice received an addtional TDNA boosting 13 weeks later. Plaque reduction neutralization tests (PRNT) were performed at 4 weeks post-last immunization. Both 100 μg and 10 μg doses of TDNA induced high NAb levels against all DENV serotypes. The median PRNT50 titers were comparable among four serotypes of DENV after TDNA immunization. Median PRNT50 titers ranged 240–320 in 100 μg and 160–240 in 10 μg groups (p = ns). A time course study of the 100 μg dose of TDNA showed detectable NAb at 2 weeks after the second injection. The NAb peaked at 4 weeks after the third injection then declined over time but remained detectable up to 13 weeks. An additional homologous TDNA boosting significantly enhanced the level of NAb from the nadir for at least ten-fold (p<0.05). Of interest, we have found that the use of more recent dengue viral strain for both vaccine immunogen design and neutralization assays is critical to avoid a mismatching outcome. In summary, this TDNA vaccine candidate induced good neutralizing antibody responses in mice; and the DNA/DNA prime/boost strategy is promising and warranted further evaluation in non-human primates.
Epitope-Based Vaccines with the Anaplasma marginale MSP1a Functional Motif Induce a Balanced Humoral and Cellular Immune Response in Mice  [PDF]
Paula S. Santos, Angela A. S. Sena, Rafael Nascimento, Thaise G. Araújo, Mirian M. Mendes, Jo?o R. S. Martins, Tiago W. P. Mineo, José R. Mineo, Luiz R. Goulart
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060311
Abstract: Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based approach in mice. Mice infection with bovine anaplasmosis was demonstrated by qPCR analysis of erythrocytes after 15-day exposure. A proof-of-concept was obtained in this murine model, in which peptides conjugated to bovine serum albumin were used for immunization in three 15-day intervals by intraperitoneal injections before challenging with live bacteria. Blood samples were analyzed for the presence of specific IgG2a and IgG1 antibodies, as well as for the rickettsemia analysis. A panel containing the cytokines’ transcriptional profile for innate and adaptive immune responses was carried out through qPCR. Immunized BALB/c mice challenged with A. marginale presented stable body weight, reduced number of infected erythrocytes, and no mortality; and among control groups mortality rates ranged from 15% to 29%. Additionally, vaccines have significantly induced higher IgG2a than IgG1 response, followed by increased expression of pro-inflammatory cytokines. This is a successful demonstration of epitope-based vaccines, and protection against anaplasmosis may be associated with elicitation of effector functions of humoral and cellular immune responses in murine model.
Immunological properties of gene vaccines delivered by different routes
Oliveira, S.C.;Rosinha, G.M.S.;de-Brito, C.F.A.;Fonseca, C.T.;Afonso, R.R.;Costa, M.C.M.S.;Goes, A.M.;Rech, E.L.;Azevedo, V.;
Brazilian Journal of Medical and Biological Research , 1999, DOI: 10.1590/S0100-879X1999000200009
Abstract: gene vaccines represent a new and promising approach to control infectious diseases, inducing a protective immune response in the appropriate host. several routes and methods of genetic immunization have been shown to induce antibody production as well as t helper (th) cell and cytotoxic t lymphocyte activation. however, few studies have compared the nature of the immune responses generated by different gene vaccination delivery systems. in the present study we reviewed some aspects of immunity induced by gene immunization and compared the immune responses produced by intramuscular (im) dna injection to gene gun-mediated dna transfer into the skin of balb/c mice. using a reporter gene coding for ?-galactosidase, we have demonstrated that im injection raised a predominantly th1 response with mostly igg2a anti-?gal produced, while gene gun immunization induced a mixed th1/th2 profile with a balanced production of igg2a and igg1 subclasses. distinct types of immune responses were generated by different methods of gene delivery. these findings have important implications for genetic vaccine design. firstly, a combination between these two systems may create optimal conditions for the induction of a broad-based immune response. alternatively, a particular gene vaccine delivery method might be used according to the immune response required for host protection. here, we describe the characteristics of the immune response induced by gene vaccination and the properties of dna involved in this process.
Immunological properties of gene vaccines delivered by different routes  [cached]
Oliveira S.C.,Rosinha G.M.S.,de-Brito C.F.A.,Fonseca C.T.
Brazilian Journal of Medical and Biological Research , 1999,
Abstract: Gene vaccines represent a new and promising approach to control infectious diseases, inducing a protective immune response in the appropriate host. Several routes and methods of genetic immunization have been shown to induce antibody production as well as T helper (Th) cell and cytotoxic T lymphocyte activation. However, few studies have compared the nature of the immune responses generated by different gene vaccination delivery systems. In the present study we reviewed some aspects of immunity induced by gene immunization and compared the immune responses produced by intramuscular (im) DNA injection to gene gun-mediated DNA transfer into the skin of BALB/c mice. Using a reporter gene coding for -galactosidase, we have demonstrated that im injection raised a predominantly Th1 response with mostly IgG2a anti- gal produced, while gene gun immunization induced a mixed Th1/Th2 profile with a balanced production of IgG2a and IgG1 subclasses. Distinct types of immune responses were generated by different methods of gene delivery. These findings have important implications for genetic vaccine design. Firstly, a combination between these two systems may create optimal conditions for the induction of a broad-based immune response. Alternatively, a particular gene vaccine delivery method might be used according to the immune response required for host protection. Here, we describe the characteristics of the immune response induced by gene vaccination and the properties of DNA involved in this process.
An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock  [cached]
Morefield Garry L,Tammariello Ralph F,Purcell Bret K,Worsham Patricia L
Journal of Immune Based Therapies and Vaccines , 2008, DOI: 10.1186/1476-8518-6-5
Abstract: Background Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy. Methods As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures. Results The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B. Conclusion Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component. The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product.
Histopathological Changes in Skin and Lymph Nodes of Sheep Following Vaccination with Anthrax, Capripox and Combined and Anthrax and Capripox Vaccines
Abbas Mohamed Ahmed,A.M. Zakia,M.M. Mukhtar,A.M. El-Hussein
Journal of Animal and Veterinary Advances , 2012,
Abstract: Skin sections of sheep inoculated with live spores anthrax vaccine revealed edema, intense effusion of mononuclear cells and proliferation fibroblast in the dermis and subcutaneous tissues, whereas sections of skin of those inoculated with capripox vaccine showed hyperplasia and hydrophopic degeneration of epidermal epithelium and instance infilteration of cellular exudates in dermis and subcutaneous tissues. However, the lesions presented by the combined vaccine included the fore mentioned lesions.
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