Vaccines (Dec 2023)

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

  • Monique Ribeiro de Lima,
  • Ana Cristina C. S. Leandro,
  • Andreia Lamoglia de Souza,
  • Marcio Mantuano Barradas,
  • Eric Henrique Roma,
  • Ana Teresa Gomes Fernandes,
  • Gabrielle Galdino-Silva,
  • Joyce Katiuccia M. Ramos Carvalho,
  • Renato Sergio Marchevsky,
  • Janice M. C. Oliveira Coelho,
  • Eduardo Dantas Casillo Gonçalves,
  • John L. VandeBerg,
  • Celio Lopes Silva,
  • Maria da Gloria Bonecini-Almeida

DOI
https://doi.org/10.3390/vaccines11121863
Journal volume & issue
Vol. 11, no. 12
p. 1863

Abstract

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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 the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day 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 provides 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.

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