Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys

Monique Ribeiro de Lima
,
Ana Cristina C.S. Leandro
ORCID logo ,
Andreia Lamoglia Souza
,
Marcio Mantuano Barradas
,
Eric Henrique Roma
,
Ana Teresa Gomes Fernandes
,
Gabrielle Galdino-Silva
,
Joyce Katiuccia M. Ramos Carvalho
,
Renato Sérgio Marchevisky
,
Janice M C Oliveira Coelho
,
Eduardo Dantas Casillo Gonçalves
,
John L. VandeBerg
,
Celio Lopes Silva
,
Maria da Gloria Bonecini-Almeida
*
Version 1 : Received: 20 October 2023 / Approved: 23 October 2023 / Online: 23 October 2023 (11:15:50 CEST)

A peer-reviewed article of this Preprint also exists.

de Lima, M.R.; Leandro, A.C.C.S.; de Souza, A.L.; Barradas, M.M.; Roma, E.H.; Fernandes, A.T.G.; Galdino-Silva, G.; Carvalho, J.K.M.R.; Marchevsky, R.S.; Coelho, J.M.C.O.; Gonçalves, E.D.C.; VandeBerg, J.L.; Silva, C.L.; Bonecini-Almeida, M.G. Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys. Vaccines 2023, 11, 1863. de Lima, M.R.; Leandro, A.C.C.S.; de Souza, A.L.; Barradas, M.M.; Roma, E.H.; Fernandes, A.T.G.; Galdino-Silva, G.; Carvalho, J.K.M.R.; Marchevsky, R.S.; Coelho, J.M.C.O.; Gonçalves, E.D.C.; VandeBerg, J.L.; Silva, C.L.; Bonecini-Almeida, M.G. Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys. Vaccines 2023, 11, 1863.

Abstract

A Bacille Calmette-Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-days intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low, and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provided limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime-boost regimen, to help the induction of a stronger cellular immune response.

Keywords

tuberculosis; electroporation; vaccine; DNA-hsp65; nonhuman primate

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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