Development and assessment of a new cage-like particle adjuvant

Author:

Bertona Daiana1,Pujato Nazarena1,Bontempi Iván1,Gonzalez Verónica23,Cabrera Gabriel12,Gugliotta Luis23,Hozbor Daniela4,Nicastro Alcides5,Calvinho Luis6,Marcipar Iván Sergio12ORCID

Affiliation:

1. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

2. Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina

3. INTEC (Universidad Nacional del Litoral and CONICET), Santa Fe, Argentina

4. Laboratorio VacSal, Facultad de Ciencias Exactas, Instituto de Biotecnología y Biología Molecular, CCT La Plata CONICET, Universidad Nacional de La Plata, Buenos Aires, Argentina

5. LIPOMIZE SRL Santa Fe Argentina, Santa Fe, Argentina

6. Estación Experimental Agropecuaria Rafaela, Santa Fe, Argentina

Abstract

Abstract Objectives To obtain and assess stable cage-like particles with low surface charge density, which can be prepared using a standardized, economic and scalable method. Methods To form these nanoparticles, the lipid composition and proportion as well the method were modified in relation to cage-like particles previously described elsewhere. Bovine albumin was used to compare ISPA performance with that of other adjuvants in mice and to assess stability. Adjuvant efficacy was analysed using a mouse model of Trypanosoma cruzi infection, which shows protection against an intracellular infection that needs a strong cellular response. Key findings The new particles were better in terms of level, kinetics and profile of humoral responses than Freund Adjuvant, aluminium hydroxide and Montanide TM ISA 206; they also tended to improve ISCOMATRIX™ performance. Particle size and adjuvant performance were conserved during the 6-month period assessed after preparation. In the model of Trypanosoma cruzi infection, mice immunized with ISPA and trans-sialidase developed high protection. Conclusions The obtained nanoparticles were stable and outperformed the other assessed adjuvants in joining together the capacity of most adjuvants to enhance the immune response against specific antigen, to reduce the number of doses, to homogenize the response between individuals and to reach a balanced TH1/TH2 response.

Funder

Argentine National Agency for the Promotion of Science and Technology

National Scientific and Technical Research Council

Universidad Nacional del Litoral, Argentina

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference34 articles.

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2. Mechanisms of action of adjuvants;Awate;Front Immunol,2013

3. Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses;Morein;Nature,1984

4. ISCOMs and ISCOMATRIX;Sun;Vaccine,2009

5. Meta-analysis on randomized controlled trials of vaccines with qs-21 or iscomatrix adjuvant: safety and tolerability;Bigaeva;PLoS ONE,2016

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