Research
Polyclonal antibodies
At Inmunova we have wide experience in the research of biological therapies based on polyclonal antibodies.
Polyclonal antibodies (PAbs) are a heterogeneous mixture of antibodies usually produced by different B cells clones in the body. They can recognize and bind to many different epitopes of a single antigen. PAbs act by quickly recognizing and neutralizing the virus or toxin, thus avoiding the disease’s progression.
EpAbs technology is used to develop medicines, treat medical emergencies such as snakebite and scorpion sting envenomation, severe poisoning (tetanus toxin, digoxin, and more recently, botulinum toxin) and severe infectious diseases like avian influenza.
Unlike monoclonal antibodies that attack the infectious agent by targeting a limited region, polyclonal antibodies recognize and attack different regions of the virus, which allows them to remain effective against possible mutations. The anti-SARS-CoV-2 hyperimmune serum based on EpAbs and developed by Inmunova demonstrated this, since in vitro viral seroneutralization assays showed its neutralizing capacity against Omicron, Delta, Gamma and Alpha variants.
Furthermore, EpAbs can be produced rapidly on a large scale.
Scientific publications
The science is in our DNA and is the base of everything we do.
We cultivate a culture of scientific excellence and innovation and we communicate our findings in specialized journals with peer reviews.
Hemolytic uremic syndrome
«Serology as an early diagnostic tool in pediatric patients with Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome: a post hoc analysis of a phase 2 clinical trial»
Stella M Landivar, Luciano J Melli, Mariana Pichel, Marta Rivas, Mariana Colonna, Carolina Massa, Vanesa Zylberman, Santiago Sanguineti, Linus Spatz, Fernando Goldbaum, Diego J Comerci, Juan E Ugalde, Andrés E Ciocchini; INM004 Study Group. PubMed.
“Cryo-EM structures of engineered Shiga toxin-based immunogens capable of eliciting neutralizing antibodies with therapeutic potential against hemolytic uremic syndrome»
Alejandro Ezequiel Cristófalo, Arvind Sharma, María Laura Cerutti, Kedar Sharma, Roberto Melero, Romina Pardo, Fernando Alberto Goldbaum, Mario Borgnia, Vanesa Zylberman, Lisandro Horacio Otero. Wiley.
“Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome»
by Marta Rivas 1,Mariana Pichel 1,Vanesa Zylberman 1,2,Mariana Colonna 1ORCID,Marina Valerio 1,Carolina Massa 1,Romina Pardo 1,Andrés E. Ciocchini 2,3,Santiago Sanguineti 1,Ian Roubicek 1,Linus Spatz 1 andFernando Alberto Goldbaum 1,2,*. MDPI
“Open-label, controlled, phase 2 clinical trial assessing the safety, efficacy, and pharmacokinetics of INM004 in pediatric patients with Shiga toxin-producing Escherichia coli–associated hemolytic uremic syndrome». Fayad, A., Principi, I., Balestracci, A., Alconcher, L., Coccia, P., Adragna, M., Amoreo, O., Bettendorff, M. C., Blumetti, M. V., Bonany, P., Tonfi, M. L. F., Flynn, L., Ghezzi, L., Montero, J., Ramírez, F., Seminara, C., Suarez, Á., Spizzirri, A. P., Rivas, M., & Pichel, M. (2024). Pediatric Nephrology.
“A phase I study to evaluate the safety, tolerance and pharmacokinetics of anti‐Shiga toxin hyperimmune equine F (ab′)2 fragments in healthy volunteers».Yanina Hiriart, Scibona, P., Ferraris, A., Belloso, W. H., Beruto, V., Facundo Garcia Bournissen, Zylberman, V., Muñoz, L., Goldbaum, F., Spatz, L., Colonna, M., Sanguineti, S., & Simonovich, V. A. (2024). British Journal of Clinical Pharmacology, 90(4), 1142–1151.
“Development of a anti-Shiga toxin product for prevention of the hemolytic uremic syndrome”. Hiriart Y, Pardo R, Bukata L, Lauché C, Muñoz L, Colonna M, Goldbaum F, Sanguineti S, Zylberman V. Medicina, 2018;78(2):107-112.
“Development of camelid single chain antibodies against Shiga toxin type 2 (Stx2) with therapeutic potential against Hemolytic Uremic Syndrome (HUS)”. Mejias M, Hiriart Y, Lauché C, Fernandez-Brando RJ, Pardo R, Bruballa A, Ramos MV, Goldbaum FA, Palermo M and Zylberman V. Scientific Reports, 6: 24913. 2016.
“Protection of mice against Stx2-associated damage by maternal immunization with a Brucella Lumazine Synthase-Stx2 B Subunit Chimera”. Mejias MP, Cabrera G, Fernández-Brando RJ, Baschkier A, Ghersi G, Abrey-Recalde MJ, Miliwebsky E, Meiss R, Goldbaum FA, Zylberman V, Rivas M, Palermo MS. Infection and Immunity, (82-4, 1491-1499) 2014.
“Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice”. Mejias MP, Ghersi G, Craig PO, Panek CA, Bentancor LV, Baschkier A, Goldbaum FA, Zylberman V and Palermo MS. The Journal of Immunology, 191(5):2403-2411, 2013.
“Polymeric Display of Proteins through High Affinity Leucine Zipper Peptide Adaptors”. Craig PO, Alzogaray V and Goldbaum FA. Biomacromolecules, 13(4):1112-1121, 2012.
Hantavirus
“Hantavirus GnH Nanoparticle Immunogen Elicits a Cross-Neutralizing Antibody Response in Mice»
Kevin E Ramos. Margarette C Mariano. Eva Mittler. Romina Pardo. Vanessa Zylberman. Pablo Guardado-Calvo. Kartik Chandran. Jonathan R Lai. PubMed.
COVID-19
“Safety and effectiveness of RBD-specific polyclonal equine F(ab´)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: A retrospective cohort study”. Farizano Salazar DH, Achinelli F, Colonna M, Pérez L, Giménez AA, et al. (2022). PLOS ONE 17(9): e0274796. https://doi.org/10.1371/journal.pone.0274796
“Non-clinical safety assessment and and in vivo biodistribution of CoviFab, an RBD-specific F(ab’)2 fragment derived from equine polyclonal antibodies”. F. Salinas et al. Toxicology and Applied Pharmacology, Volume 434 (2022) 115796.
“RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial”. G. Lopardo et al. EClinicalMedicine, 34 (2021) 100843.
“Development of a Hyperimmune Equine Serum Therapy for COVID-19 in Argentina”. Zylberman, V., Sanguineti, S., Pontoriero, A. V., Higa, S. V., Cerutti, M. L., Morrone Seijo, S. M., et al. Medicina, (Buenos Aires) 2020; Vol. 80 (Supl. III): 1-6.
BLS Technology
“Evaluation of the efficacy of polymeric antigen BLSOmp31 formulated in a new cage-like particle adjuvant (ISPA) administered by parenteral or mucosal routes against Brucella ovis in BALB/c mice”. María Celeste Moran, María Paula Dominguez, Angel Ricardo Bence, Marcelo Gastón Rodriguez, Fernando Alberto Goldbaum, Vanesa Zylberman, Pardo Romina Paola, Giuliana Lupi, Ivan Sergio Marcipar, Claudia María Lützelschwab, Silvia Marcela Estein. PubMed
“Mucosal immunization with polymeric antigen BLSOmp31 using alternative delivery systems against Brucella ovis in rams”. Alejandra Graciela Díaz, Daniela Alejandra Quinteros, Fernando Alberto Paolicchi, Mariana Alejandra Rivero, Santiago Daniel Palma, Romina Paola Pardo, María Clausse, Vanesa Zylberman, Fernando Alberto Goldbaum, Silvia Marcela Estein. PubMed
“The polymeric antigen BLSOmp31 confers protection against Brucella ovis infection in rams”. Silvia M Estein, María A Fiorentino, Fernando A Paolicchi, María Clausse, Jorge Manazza, Juliana Cassataro, Guillermo H Giambartolomei, Lorena M Coria, Vanesa Zylberman, Carlos A Fossati, Rune Kjeken, Fernando A Goldbaum. PubMed
“Spray dried microspheres based on chitosan: A promising new carrier for intranasal administration of polymeric antigen BLSOmp31 for prevention of ovine brucellosis”. Alejandra Graciela Díaz, Daniela Alejandra Quinteros, Juan Manuel Llabot, Santiago Daniel Palma, Daniel Alberto Allemandi, Giselle Ghersi, Vanesa Zylberman, Fernando Alberto Goldbaum, Silvia Marcela Estein. PubMed
“Immune response and serum bactericidal activity against Brucella ovis elicited using a short immunization schedule with the polymeric antigen BLSOmp31 in rams”. Alejandra G Díaz, María Clausse, Fernando A Paolicchi, María A Fiorentino, Giselle Ghersi, Vanesa Zylberman, Fernando A Goldbaum, Silvia M Estein. PubMed
“Immune response induced by conjunctival immunization with polymeric antigen BLSOmp31 using a thermoresponsive and mucoadhesive in situ gel as vaccine delivery system for prevention of ovine brucellosis”. Alejandra Graciela Díaz, Daniela Alejandra Quinteros, Silvina Elena Gutiérrez, Mariana Alejandra Rivero, Santiago Daniel Palma, Daniel Alberto Allemandi, Romina Paola Pardo, Vanesa Zylberman, Fernando Alberto Goldbaum, Silvia Marcela Estein. PubMed
“Polymeric antigen BLSOmp31 formulated with class B CpG-ODN in a nanostructure (BLSOmp31/CpG-ODN/Coa-ASC16) administered by parenteral or mucosal routes confers protection against Brucella ovis in Balb/c mice”. María Celeste Moran, Angel Ricardo Bence, María Fernanda Sánchez Vallecillo, Claudia María Lützelschwab, Marcelo Gastón Rodriguez, Romina Pardo, Fernando Alberto Goldbaum, Vanesa Zylberman, Santiago Daniel Palma, Belkys Angélica Maletto, Silvia Marcela Estein. PubMed
“Evaluation of the efficacy of polymeric antigen BLSOmp31 formulated in a new cage-like particle adjuvant (ISPA YOLK) administered by parenteral or mucosal routes against Brucella ovis in rams”. María Celeste Moran, Agostina Tammone Santos, Paula Dominguez, Lucila Moriones, María Victoria Nieto Farias, Laura Maté, Juan Agustín García, Tobias Kuhn , Fernando Alberto Paolicchi, María Andrea Fiorentino, Marcelo Gastón Rodriguez, Jorge Pablo García, Claudio Santiago Cacciato, Fernando Alberto Goldbaum, Vanesa Zylberman, Romina Paola Pardo, Sabrina Foscaldi, Claudia María Lützelschwab, Giuliana Lupi, Iván Santiago Marcipar, Silvia Marcela Estein. PubMed
“Polymeric antigen BLSOmp31 in aluminium hydroxide induces serum bactericidal and opsonic antibodies against Brucella canis in dogs”. Maria Clausse, Alejandra G Díaz, Romina P Pardo, Vanesa Zylberman, Fernando A Goldbaum, Silvia M Estein. PubMed
“The vaccine candidate BLSOmp31 protects mice against Brucella canis infection”. Maria Clausse, Alejandra G Díaz, Giselle Ghersi, Vanesa Zylberman, Juliana Cassataro, Guillermo H Giambartolomei, Fernando A Goldbaum, Silvia M Estein. PubMed
“Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein”. Nicolas Torres, María Victoria Regge, Florencia Secchiari, Adrián David Friedrich, Raúl Germán Spallanzani, Ximena Lucía Raffo Iraolagoitia, Sol Yanel Núñez, Jessica Mariel Sierra, Andrea Ziblat, María Cecilia Santilli, Nicolás Gilio, Evangelina Almada, Constanza Lauche, Romina Pardo 2, Carolina Inés Domaica, Mercedes Beatriz Fuertes, Kevin Patrick Madauss, Kenneth W Hance, Israel S Gloger, Vanesa Zylberman, Fernando Alberto Goldbaum, Norberto Walter Zwirner. PubMed
“Multiple display of a protein domain on a bacterial polymeric scaffold”. Craig, P. O., Berguer, P. M., Ainciart, N., Zylberman, V., Thomas, M. G , Martinez Tosar, L. J., Bulloj, A., Boccaccio, G.L. and Goldbaum, F. A. Proteins, Structure, Function and Bioinformatics, 1;61(4):1089-1100, 2005.
“Brucella spp. lumazine synthase: a novel antigen delivery system” Sciutto, E., Toledo, A., Cruza, C., Rosas, G., Meneses, G., Laplagne, D., Ainciart, N., Cervantes, J., Fragoso, G. and Goldbaum, F. A. Vaccine, 23(21):2784-90, 2005.
“Engineering of a polymeric bacterial protein as a scaffold for the multiple display of peptides”. Laplagne, D. A., Zylberman, V., Ainciart, N., Steward M. W., Sciutto, E., Fossati, C. A. and Goldbaum, F. A. Proteins, Structure, Function and Bioinformatics, 57(4):820-828, 2004.
“High order quaternary arrangement confers increased stability to Brucella spp. lumazine synthase”. Zylberman, V., Craig, P., Klinke S., Braden, B.C., Cauerhff, A. and Goldbaum F. A. Journal of Biological Chemistry, 279(9):8093-8101, 2004.
VHH
“Development and Evaluation of a Novel VHH-Based Immunocapture Assay for High-Sensitivity Detection of Shiga Toxin Type 2 (Stx2) in Stool Samples”. Luciano J Melli, Vanesa Zylberman, Yanina Hiriart, Constanza E Lauche, Ariela Baschkier, Romina Pardo, Elizabeth Miliwebsky, Isabel Chinen, Marta Rivas, Fernando A Goldbaum, Juan E Ugalde, Diego J Comerci, Andrés E Ciocchini. PubMed
“Development of camelid single chain antibodies against Shiga toxin type 2 (Stx2) with therapeutic potential against Hemolytic Uremic Syndrome (HUS)”. Maria P Mejías, Yanina Hiriart, Constanza Lauché, Romina J Fernández-Brando, Romina Pardo, Andrea Bruballa, María V Ramos, Fernando A Goldbaum, Marina S Palermo, Vanesa Zylberman. PubMed
Influenza
“Tandem repeats of the extracellular domain of Matrix 2 influenza protein exposed in Brucella lumazine synthase decameric carrier molecule induce protection in mice”. Paula Alvarez, Vanesa Zylberman, Giselle Ghersi, Lorena Boado, Carlos Palacios, Fernando Goldbaum, Nora Mattion. PubMed
Patents
“Isolated chimeric proteins of modified lumazine synthase”. PCT WO 2005/121330, Diciembre 2005. Fernando Alberto Goldbaum, Diego Andres Laplagne, Vanesa Zylberman, Patricio Craig, Paula Mercedes Berguer, Natalia Ainciart, Carlos Alberto Fossati, Carlos Alejandro Velikovsky, Juliana Cassataro, Guillermo Giambartolomei.
“Chimeras of Brucella lumazine synthase and beta subunit of AB5 toxins”, filed on May 26, 2014, under No. PCT/IB2014/061731, Goldbaum, Fernando; Zylberman, Vanesa; Craig, Patricio; Ghersi, Giselle; Palermo, Marina; Mejías, Pilar; Bentancor. Titulares Inmunova S.A. / Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).
