http://www.jibtherapies.com The latest research articles published by Journal of Immune Based Therapies and Vaccines 2010-02-05T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Studies have shown that CpG oligodeoxyribonucleotides (ODN) protect mice from various bacterial pathogens, including Burkholderia pseudomallei and Francisella tularensis live vaccine strain (LVS), when administered before parenteral challenge. Given the potential to develop CpG ODN as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from CpG ODN-treated C57BL/6 mice to determine whether previously-reported protection extended to aerosolized B. pseudomallei 1026b and highly virulent F. tularensis Schu S4 infections. We found that, although CpG ODN protected mice from aerosolized B. pseudomallei challenges, the immunostimulant failed to benefit the animals exposed to F. tularensis Schu S4 aerosols. Our results, which contrast with earlier F. tularensis LVS studies, highlight potential differences in Francisella species pathogenesis and underscore the need to evaluate immunotherapies against human pathogenic species. http://www.jibtherapies.com/content/8/1/2 David Rozak Herbert Gelhaus Mark Smith Mojgan Zadeh Louis Huzella David Waag Jeffrey Adamovicz Journal of Immune Based Therapies and Vaccines 2010, 8:2 2010-02-05T00:00:00Z doi:10.1186/1476-8518-8-2 Journal of Immune Based Therapies and Vaccines 1476-8518 8 2 2010-02-05T00:00:00Z XML Active vaccination can be effective as a post-exposure prophylaxis, but the rapidity of the immune response induced, relative to the incubation time of the pathogen, is critical. We show here that CD40mAb conjugated to antigen induces a more rapid specific antibody response than currently used immunological adjuvants, alum and monophosphoryl lipid A™. http://www.jibtherapies.com/content/8/1/1 Vijay Bhagawati-Prasad Evy DeLeenheer Nadine Keefe Lorna Ryan Jennifer Carlring Andrew Heath Journal of Immune Based Therapies and Vaccines 2010, 8:1 2010-02-04T00:00:00Z doi:10.1186/1476-8518-8-1 Journal of Immune Based Therapies and Vaccines 1476-8518 8 1 2010-02-04T00:00:00Z XML Background: Conserved neutralizing epitopes are considered to be a key role for eliciting broadly neutralizing antibody (NAb). Previously, two conserved neutralizing epitopes of HIV-1 CRF01_AE envelope were identified at amino acid 93-112 of the C1 (C1E) and at 218-239 of the C2 (C2E) regions. To access the potency of antibody directed against conserved epitopes, a monoclonal antibody (MAb) specific to the C2E region was developed and characterized. Methods: The immunogenicity of two epitopes was examined by immunizing BALB/c mice with the matching synthetic peptides. One MAb, C2EB5, directed against peptide C2E, was generated by conventional methods, while C1E1 and C1E2 peptides induced slight antibody response in mice. The neutralizing activity of MAb C2EB5 was examined using a peripheral blood mononuclear cell (PBMC) based method and various HIV-1 subtypes including A, B, C, D, and CRF01_AE; C2EB5 was compared with other known neutralizing MAbs (4E10, 447-52D) and with sCD4. The exposure of the C2 epitope on native virus was investigated using virus capture by these MAbs. Results: The MAb C2EB5 demonstrated cross-neutralization against various HIV-1 subtypes. The overall potency of MAb C2EB5 against 5 subtypes was ranked in the following order: subtype C> CRF01_AE> subtype D> subtype A> subtype B. The epitope exposure for MAb C2EB5 was also correlated with the neutralization properties of each subtype. Conclusion: This study demonstrates the cross-clade neutralizing activity of a MAb directed against an epitope located in the C2 region of the HIV-1 env and highlights differences in the exposure of antigenic epitopes on the surface of various HIV-1 subtypes. The epitope for this newly identified neutralizing MAb made against a subtype CRF01_AE peptide is particularly exposed in subtype C viral isolates. http://www.jibtherapies.com/content/7/1/5 Apichai Sreepian Jongruk Permmongkol Wannee Kantakamalakul Sontana Siritantikorn Nattaya Tanlieng Ruengpung Sutthent Journal of Immune Based Therapies and Vaccines 2009, 7:5 2009-10-12T00:00:00Z doi:10.1186/1476-8518-7-5 Journal of Immune Based Therapies and Vaccines 1476-8518 7 5 2009-10-12T00:00:00Z XML Background: Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases. Methods: In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ. Results: DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete. Conclusion: The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases. http://www.jibtherapies.com/content/7/1/4 Rubens Santos-Junior Alexandrina Sartori Deison Lima Patricia Souza Arlete Coelho-Castelo Vania Bonato Celio Silva Journal of Immune Based Therapies and Vaccines 2009, 7:4 2009-09-15T00:00:00Z doi:10.1186/1476-8518-7-4 Journal of Immune Based Therapies and Vaccines 1476-8518 7 4 2009-09-15T00:00:00Z XML Experiments almost 20 years ago demonstrated that injections of a sequence of DNA encoding part of a pathogen could stimulate immunity. It was soon realized that "DNA vaccination" had numerous potential advantages over conventional vaccine approaches including inherent safety and a more rapid production time. These and other attributes make DNA vaccines ideal for development against emerging pathogens. Recent advances in optimizing various aspects of DNA vaccination have accelerated this approach from concept to reality in contemporary human trials. Although not yet licensed for human use, several DNA vaccines have now been approved for animal health indications. The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Because of recent advances in DNA vaccination, this approach has the potential to be a powerful new weapon in protecting against emerging and potentially pandemic human pathogens. http://www.jibtherapies.com/content/7/1/3 Ronald Moss Journal of Immune Based Therapies and Vaccines 2009, 7:3 2009-09-07T00:00:00Z doi:10.1186/1476-8518-7-3 Journal of Immune Based Therapies and Vaccines 1476-8518 7 3 2009-09-07T00:00:00Z XML Influenza viruses pose a permanent threat to human populations due to their ability to constantly adapt to impact immunologically susceptible individuals in the forms of epidemic and pandemics through antigenic drifts and antigenic shifts, respectively. Pandemic influenza preparedness is a critical step in responding to future influenza outbreaks. In this regard, responding to the current pandemic and preparing for future ones requires critical planning for the early phases where there is no availability of pandemic vaccine with rapid deployment of medical supplies for personal protection, antivirals, antibiotics and social distancing measures. In addition, it has become clear that responding to the current pandemic or preparing for future ones, nation states need to develop or strengthen their laboratory capability for influenza diagnosis as well as begin preparing their vaccine/antiviral deployment plans. Vaccine deployment plans are the critical missing link in pandemic preparedness and response. Rapid containment efforts are not effective and instead mitigation efforts should lead pandemic control efforts. We suggest that development of vaccine/antiviral deployment plans is a key preparedness step that allows nations identify logistic gaps in their response capacity. http://www.jibtherapies.com/content/7/1/2 Carlos Franco-Paredes Peter Carrasco Jose Ignacio Santos-Preciado Journal of Immune Based Therapies and Vaccines 2009, 7:2 2009-08-07T00:00:00Z doi:10.1186/1476-8518-7-2 Journal of Immune Based Therapies and Vaccines 1476-8518 7 2 2009-08-07T00:00:00Z XML Background: There is no safe, effective human vaccine against brucellosis. Live attenuated Brucella strains are widely used to vaccinate animals. However these live Brucella vaccines can cause disease and are unsafe for humans. Killed Brucella or subunit vaccines are not effective in eliciting long term protection. In this study, we evaluate an approach using a live, non-pathogenic bacteria (E. coli) genetically engineered to mimic the brucellae pathway of infection and present antigens for an appropriate cytolitic T cell response. Methods: E. coli was modified to express invasin of Yersinia and listerialysin O (LLO) of Listeria to impart the necessary infectivity and antigen releasing traits of the intracellular pathogen, Brucella. This modified E. coli was considered our vaccine delivery system and was engineered to express Green Fluorescent Protein (GFP) or Brucella antigens for in vitro and in vivo immunological studies including cytokine profiling and cytotoxicity assays. Results: The E. coli vaccine vector was able to infect all cells tested and efficiently deliver therapeutics to the host cell. Using GFP as antigen, we demonstrate that the E. coli vaccine vector elicits a Th1 cytokine profile in both primary and secondary immune responses. Additionally, using this vector to deliver a Brucella antigen, we demonstrate the ability of the E. coli vaccine vector to induce specific Cytotoxic T Lymphocytes (CTLs). Conclusion: Protection against most intracellular bacterial pathogens can be obtained mostly through cell mediated immunity. Data presented here suggest modified E. coli can be used as a vaccine vector for delivery of antigens and therapeutics mimicking the infection of the pathogen and inducing cell mediated immunity to that pathogen. http://www.jibtherapies.com/content/7/1/1 Jerome Harms Marina Durward Diogo Magnani Gary Splitter Journal of Immune Based Therapies and Vaccines 2009, 7:1 2009-01-06T00:00:00Z doi:10.1186/1476-8518-7-1 Journal of Immune Based Therapies and Vaccines 1476-8518 7 1 2009-01-06T00:00:00Z XML Background: The gram-positive bacterium Streptococcus pyogenes is a common pathogen of humans that causes invasive infections, toxic-shock syndrome, rheumatic fever, necrotizing fasciitis and other diseases. Detection of antibiotic resistance in clinical isolates has renewed interest in development of new vaccine approaches for control S. pyogenes sepsis. In the study presented, a novel protein vaccine was examined. The vaccine was based on a recombinant protein fusion between streptococcal pyrogenic exotoxin B (SpeB), a cysteinyl protease expressed by all clinical isolates, and streptococcal pyrogenic exotoxin A (SpeA), a superantigen produced by a large subset of isolates. Results: A novel protein was produced by mutating the catalytic site of SpeB and the receptor binding surface of SpeA in a fusion of the two polypeptides. Vaccination of HLA-DQ8 transgenic mice with the SpeA-SpeB fusion protein protected against a challenge with the wild-type SpeA that was lethal to naïve controls, and vaccinated mice were protected from an otherwise lethal S. pyogenes infection. Conclusion: These results suggest that the genetically attenuated SpeA-SpeB fusion protein may be useful for controlling S. pyogenes infections. Vaccination with the SpeA-SpeB fusion protein described in this study may potentially result in protective immunity against multiple isolates of S. pyogenes due to the extensive antibody cross-reactivity previously observed among all sequence variants of SpeB and the high frequency of SpeA-producing strains. http://www.jibtherapies.com/content/6/1/8 Robert Ulrich Journal of Immune Based Therapies and Vaccines 2008, 6:8 2008-10-31T00:00:00Z doi:10.1186/1476-8518-6-8 Journal of Immune Based Therapies and Vaccines 1476-8518 6 8 2008-10-31T00:00:00Z XML Background: Efficacious immune-based therapy in treated chronic HIV-1 infection requires the induction of virus-specific CD4+ T cells and subsequent maturation and maintenance of specific memory CD8+ T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) with highly active antiretroviral therapy (HAART) was used in chronically infected patients with lipodystrophy in an attempt to reconstitute these virus-specific T-cell responses. Methods: Individuals with chronic HIV-1 infection on HAART were enrolled on a randomized, double-blinded, placebo-controlled study to receive rhGH therapy. We assessed HIV-1-specific proliferative CD4+ and interferon-gamma (IFN-γ)-producing CD8+ T-cell responses, quantified thymic output and proviral HIV-1 DNA at the following time points: baseline; after 12 weeks of rhGH therapy; at 24 weeks, after randomization into three groups [placebo weeks 12–24 (Group A), alternate-day dosing weeks 12–24 (Group B), and twice-per-week dosing weeks 12–24 (Group C)]; and at 48 weeks after all patients had received HAART alone for the final 24 weeks. Results: We found significant increases in both proliferative CD4+ and IFN-γ-producing CD8+ HIV-1-specific T-cell responses after daily administration of rhGH. This increase was focused on HIV-1 Gag-specific T-cell responses. Following subsequent randomisation into different dosing regimens, HIV-1-specific proliferative CD4+ T-cell responses declined in patients receiving less frequent dosing of rhGH, while virus-specific IFN-γ-producing CD8+ T-cell responses were maintained for longer periods of time. There was no significant change in thymic output and the cell-associated HIV-1 DNA remained stable in most patients. An increased anti-HIV-1 Nef-specific CD4+ T-cell proliferative response was correlated to a decrease in proviral load, and an increased HIV-1 Gag-specific IFN-γ-producing CD8+ T-cell response correlated with an increase in proviral load. Conclusion: The implication of these data is that daily dosing of rhGH with HAART, in addition to improving HIV-1-associated lipodystrophy, may reverse some of the T-lymphocyte dysfunction seen in most treated HIV-1-positive patients, in a dose-dependent manner. Such immune-based therapeutic strategies used in treated, chronic HIV-1 infection may enable the induction of virus-specific CD4+ T cells essential for the subsequent 'kick-start' and expansion of virus-specific CD8+ T cells.Trial registrationGH in Lipoatrophy IMP22350. http://www.jibtherapies.com/content/6/1/7 Anna Herasimtschuk Samantha Westrop Graeme Moyle Jocelyn Downey Nesrina Imami Journal of Immune Based Therapies and Vaccines 2008, 6:7 2008-10-31T00:00:00Z doi:10.1186/1476-8518-6-7 Journal of Immune Based Therapies and Vaccines 1476-8518 6 7 2008-10-31T00:00:00Z XML Background: Alterations in serum CXCR3 ligand levels were examined in interstitial cystitis (IC) patients; similar expression patterns in serum as well as CXCR3, CXCR3 ligands, and cytokines expressed by peripheral and local leukocyte subpopulations were characterized during cyclophosphamide (CYP)-induced acute cystitis in mice. Results: Serum levels of monokine-induced by interferon-γ (IFN-γ) (MIG/CXCL9), IFN-γ-inducible protein-10 (IP-10/CXCL10), and IFN-γ-inducible T cell α chemoattractant (I-TAC/CXCL11) were elevated in patients with IC. These clinical features closely correlated with CYP-induced cystitis in mice. Serum levels of these CXCR3 ligands and local T helper type 1 (Th1) cytokines were also increased. We demonstrate that CXCR3 as well as CXCL9, CXCL10 and CXCL11 mRNA were significantly expressed by urinary bladder lymphocytes, while CXCR3 and CXCL9 transcripts were significantly expressed by iliac lymph node leukocytes following CYP treatment. We also show that the number of CD4+ T cells, mast cells, natural killer (NK) cells, and NKT cells were increased at systemic (spleen) and mucosal (urinary bladder and iliac lymph nodes) sites, following CYP-induced cystitis in mice. Importantly, CXCL10 blockade attenuated these increases caused by CYP. Conclusion: Antibody (Ab)-mediated inhibition of the most abundant serum CXCR3 ligand, CXCL10, in mice decreased the local production of CXCR3 ligands as well as Th1 cytokines expressed by local leukocytes, and lowered corresponding serum levels to reduce the severity of CYP-induced cystitis. The present study is among the first to demonstrate some of the cellular and molecular mechanisms of chemokines in cystitis and may represent new drug target for this disease. http://www.jibtherapies.com/content/6/1/6 Senthilkumar Sakthivel Udai Singh Shailesh Singh Dennis Taub Kristian Novakovic James Lillard Journal of Immune Based Therapies and Vaccines 2008, 6:6 2008-10-28T00:00:00Z doi:10.1186/1476-8518-6-6 Journal of Immune Based Therapies and Vaccines 1476-8518 6 6 2008-10-28T00:00:00Z XML