Scientists at EpiVax are widely considered to be thought-leaders in the fields of immunogenicity screening, deimmunization, immunomodulation and T cell vaccine design. They have produced a prolific volume of quality publications in top journals and continue to do so annually. Many of our papers are available on this site. (Please see the tabs to the left).
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De-immunized and Functional Therapeutic (DeFT) versions of a long lasting recombinant alpha interferon for antiviral therapy. Clin Immunol. 2017 Jan 10;176:31-41. doi: 10.1016/j.clim.2017.01.003. PMID: 28089609
Repeated IFN-α administration induces neutralizing antibodies (NAb) against the therapeutic in a significant number of patients. Associations between IFN-α immunogenicity and loss of efficacy have been described. In order to develop a safer and more efficient IFN therapy, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of 4N-IFN. Using the OptiMatrix in silico tool in ISPRI, the 4N-IFN sequence was modified to reduce HLA binding potential of specific T cell epitopes. Following verification of predictions by HLA binding assays, eight modifications were selected and integrated in three variants: 4N-IFN(VAR1), (VAR2) and (VAR3). Two of the three variants (VAR1 and VAR3) retained anti-viral function and demonstrated reduced T-cell immunogenicity in terms of T-cell proliferation and Th1 and Th2 cytokine levels, when compared to controls (commercial NG-IFN (non-glycosylated), PEG-IFN, WT-IFN and 4N-IFN). Taking into consideration the present results and previously reported immunogenicity data for commercial IFN-α2b variants, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be promising candidates for improved IFN-α therapy of HCV and HBV.
Computational vaccine design, also known as computational vaccinology, encompasses epitope mapping, antigen selection and immunogen design using computational tools. The iVAX toolkit is an integrated set of tools that has been in development since 1998 by De Groot and Martin. It comprises a suite of immunoinformatics algorithms for triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, eliminating regulatory T cell epitopes, and optimizing antigens for immunogenicity and protection against disease. iVAX has been applied to vaccine development programs for emerging infectious diseases, cancer antigens and biodefense targets.
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- De Groot AS, Ross TM, Levitz L, Messitt TJ, Tassone R, Boyle CM, Vincelli AJ, Moise L, Martin W, Knopf PM. C3d adjuvant effects are mediated through the activation of C3d-specific autoreactive T cells. Immunol Cell Biol. 2015;93(2):189-97. PMCID: PMC4323994 http://bit.ly/C3d_Adjuvants
- Hoffmann PR, Panigada M, Soprana E, Terry F, Bandar IS, Napolitano A, Rose AH, Hoffmann FW, Ndhlovu LC, Belcaid M, Moise L, De Groot AS, Carbone M, Gaudino G, Matsui T, Siccardi A, Bertino P. Preclinical development of HIvax: human survivin Highly Immunogenic vaccines. Hum Vaccin Immunother. 2015;11(7):1585-95. PMID: 26042612 http://bit.ly/Preclinical_Development_HIvax
- Eickhoff CS, Van Aartsen D, Terry FE, Meymandi SK, Traina MM, Hernandez S, Martin WD, Moise L, De Groot AS, Hoft DF. An immunoinformatic approach for identification of Trypanosoma cruzi HLA-A2-restricted CD8+ T cell epitopes. Hum Vaccin Immunother. 2015;11(9):2322-8. PMID: 26107442 http://bit.ly/Trypanosoma_cruzi_Epitopes
- Liu R, Moise L, Tassone R, Gutierrez AH, Terry FE, Sangare K, Ardito MT, Martin WD, De Groot AS. H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance. Hum Vaccin Immunother. 2015;11(9):2241-52. PMID: 26090577 http://bit.ly/H7N9_Epitopes_Mimic_Human
- Gutiérrez AH, Martin WD, Bailey-Kellogg C, Terry F, Moise L, De Groot AS. Development and validation of an epitope prediction tool for swine (PigMatrix) using the pocket profile method. BMC Bioinformatics. BMC Bioinformatics. 2015 Sep 15;16(1):290. doi: 10.1186/s12859-015-0724-8. http://bit.ly/PigMatrix_2015.
- Lu He, Anne S. De Groot, Chris Bailey Kellog. Hit-and-run, hit-and-stay, and commensal bacteria present different peptide content when viewed from the perspective of the T cell. Vaccine. 2015 Oct 1. doi: 10.1016/j.vaccine.2015.08.099. http://bit.ly/Bacterial_Camouflage_2015
- Review. Terry FE, Moise L, Martin RF, Torres M, Pilotte N, Williams SA, De Groot AS. Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases. Expert Rev Vaccines. 2015;14(1):21-35. PMID: 25193104 http://bit.ly/NTD-iVAX-2014
- Review. Moise L, Terry F, Gutierrez AH, Tassone R, Losikoff P, Gregory SH, Martin WD, De Groot AS. Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection. In: Why vaccines to HIV, HCV and Malaria have so far failed – challenges to developing vaccines against immunoregulating pathogens. Frontiers in Microbiology. 2014. Editor (Gowans). http://bit.ly/Smarter_Vaccines_2014
- Cousens LP, Moise L, De Groot AS. Novel Methods for Addressing Immunogenicity in Therapeutic Enzymes. In A. Rosenberg, B. Demeule (eds.), Biobetters, AAPS Advances. American Association of Pharmaceutical Scientists 2015 in the Pharmaceutical Sciences Series 19, DOI: 10.1007/978-1-4939-2543-8_5
- Moise L, Beseme S, Tassone R, Liu R, Kibria F, Terry F, Martin W, De Groot AS. T Cell Epitope Redundancy: Cross-conservation of the TCR-face between Pathogens and Self and its Implications for Vaccines and Autoimmunity. Expert Review of Vaccines. (Accepted for publication). Expert Review of Vaccines, 2015 (Accepted, in Press). http://bit.ly/Epitope_Redundancy_2015
- Lenny Moise, Sarah Beseme, and Anne S. De Groot. In Silico Vaccine Design: Accelerating the Response to BioThreats and Emerging Infectious Disease. IQT Quarterly, Winter 2016. Vol. 7 No. 3, 21, 2015.