Print Nanoparticle Vaccine Carrying Bacterial Polysaccharide And Protein Antigens Induces Enhanced B- And T-Cell (Il-17) Immunity
Poster Oct 03, 2014
Anton Beletskii,1 Camille Bernasconi,1 Jinny Conley, Meredith Earl,1 Gabe Fawcett,1 Jeremy Hansen,1 Lara Kelly,1 Marquita Lilly,1 Frank Malinoski,1 Joseph Marchand,1 Nicole Meyer,1 Shyam Rele,1 RiLee Robeson,1 Michele Stone,1 Ben Yerxa,1 Jeff Maisonneuve,2 Mark Alderson 2
Pneumococcus is a common organism causing invasive bacterial disease, especially in children < 2 years and elderly adults. Using nanoparticles in vaccine formulations allows for improved antigen stability and immunogenicity, but also targeted delivery and slow release. A nanoparticle vaccine consisting of pneumococcal polysaccharides (PnPs) and protein antigens (toxoids, surface proteins) has the potential to offer broader and enhanced protective immunity (antibody/cellular) against invasive pneumococcal disease and carriage/colonization. In partnership with PATH, Liquidia is developing a next generation multivalent nanoparticle polysaccharide protein vaccine for Streptococcus pneumoniae based on roll-to-roll PRINT technology. Specifically, a PRINT nanoparticle multivalent vaccine developed co-delivers 2 components – (i) key capsular polysaccharides (PnPs 1, 4, 5, 14, 6A, 19A, 23F) and (ii) pneumococcal carrier protein. Conjugation of antigens onto NPs can allow presentation of the immunogen to the immune systems in much the same way that it would be presented by the pathogen, leading to potent and specific antibody (IgG) and cellular (IL-17) immune responses against target antigens.
Preclinical vaccination studies in mice and rabbits with single and multivalent non-adjuvanted PRINT formulations produced polysaccharide-specific functional antibody (IgG and OPK) responses greater than or equivalent to Prevnar-13. Additionally, existing PRINT particle formulations were translated to all of Prevnar-13 serotypes and multiple proteins (CRM197, pneumococcal specific surface proteins and toxoids, TT), further demonstrating the wide-ranging multi-antigen formulation capability.
Antigenic multivalent PRINT nanoparticle formulations leverage precise control of size, shape and composition, sterile filterability and scalable cGMP roll-to roll manufacturing to offering a low cost and simplified manufacturing advantage over traditional conjugate vaccines. Moreover, the broad flexibility of the current PRINT approach has been applied to other antigen targets such as typhoid, and H. influenzae. The expectation is that PRINT particulate vaccines will provide potent antigen-specific humoral and cellular immune responses and will allow development of next generation vaccines against a range of infectious diseases.
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE
This abstract discusses three cases of pediatric heart transplant patients who suffered from parvovirus (B19) infection. Of these patients, two ( B & C) responded well to standard intravenous Ig therapy. Patient A however, did not respond to standard treatment and was begun on subcutaneous Ig, which effectively diminished his viral load. Thus, subcutaneous Ig infusions might serve as a second line treatment for transplant patients with parvovirus who do not respond well to the standard approach.READ MORE
Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma. AITL can be missed until lymphadenopathy develops in patients initially presenting with skin lesions, as skin biopsy may lack conclusive findings. Our case highlights the extranodal presentation of AITL with cutaneous lesions displaying the TFH phenotype.READ MORE