de Lima Monique Ribeiro, Leandro Ana Cristina C S, de Souza Andreia Lamoglia, Barradas Marcio Mantuano, Roma Eric Henrique, Fernandes Ana Teresa Gomes, Galdino-Silva Gabrielle, Carvalho Joyce Katiuccia M Ramos, Marchevsky Renato Sergio, Coelho Janice M C Oliveira, Gonçalves Eduardo Dantas Casillo, VandeBerg John L, Silva Celio Lopes, Bonecini-Almeida Maria da Gloria
Laboratory of Immunology and Immunogenetic in Infectious Diseases, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, RJ, Brazil.
Division of Human Genetics, South Texas Diabetes and Obesity Institute, The University of Texas Rio Grande Valley, Brownsville, TX 78520, USA.
Vaccines (Basel). 2023 Dec 18;11(12):1863. doi: 10.3390/vaccines11121863.
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.
卡介苗（BCG）仍然是唯一获得许可用于预防结核病的疫苗，在成年期对结核分枝杆菌感染提供有限的保护。在过去十年中，通过电穿孔递送DNA疫苗取得了新进展。我们评估了在食蟹猴中通过肌肉内电穿孔（EP）接种DNA-hsp65疫苗的安全性和免疫原性。动物每隔30天接受三剂DNA-hsp65。我们证明，与接种疫苗前的参数相比，食蟹猴肌肉内电穿孔DNA-hsp65疫苗免疫是安全的，并且对血液学、肾脏或肝脏指标没有疫苗相关影响。未发现结核菌素皮肤试验转化或肺部X光改变。此外，主要在第三剂DNA-hsp65疫苗后观察到低水平和短暂的外周细胞免疫反应及细胞因子表达。电穿孔DNA-hsp65疫苗接种是安全的，但对外周细胞免疫反应的增强有限。通过EP递送DNA-hsp65的临床前疫苗试验可能包括质粒细胞因子佐剂和/或蛋白初免-加强方案的组合，以帮助诱导更强的细胞免疫反应。
