Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system
Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system
复制标题
DOI：
10.1016/j.vaccine.2006.05.094
复制
发表时间：
2006-09-11
期刊：
影响因子：
5.5
通讯作者：
Hohmann, Elizabeth L.
中科院分区：
文献类型：
--
作者：
Kotton, Camille N.;Lankowski, Alexander J.;Hohmann, Elizabeth L.
背景资料：CKS 257（Sabnonella typhimurium SL 1344 Delta phoP/phoQ Delta aroA Delta asd Delta strA/strB pSB 2131）是一种表达HIV Gag的口服活疫苗载体。18名健康成年人单次口服递增剂量的5 × 10（6）至1 × 10（10）CFU的CKS 257，并监测临床事件、脱落和免疫应答。志愿者平均脱落5.1天（范围0-13天）。83%（15/18）的受试者对沙门氏菌LPS和鞭毛有粘膜免疫应答。72%（13/18）的受试者血清转化为沙门氏菌抗原。通过血清学、伊加ELISPOT或对Gag肽池的即时离体γ-干扰素ELISPOT应答测量，没有志愿者对重组Gag有应答。通过IL-2 ELISPOT，两名志愿者对Gag肽有应答，在培养的γ-干扰素ELISPOT测定中，10名接受≥ 5 × 10（8）CFU的志愿者中有4名对HIV肽有应答。结论：尽管HIV抗原的免疫原性需要增强，但减毒沙门氏菌菌株被证明是疫苗开发的极好平台。(c)2006爱思唯尔有限公司保留所有权利。
Background: CKS257 (Sabnonella typhimurium SL1344 Delta phoP/phoQ Delta aroA Delta asd Delta strA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag.Methods: HIV Gag was expressed as a fusion protein of a Salmonella Type III secretion system protein SopE, from a balanced lethal asd-based plasmid. Eighteen healthy adults were given single escalating oral doses of 5 x 10(6) to 1 x 10(10) CFU of CKS257 and were monitored for clinical events, shedding and immune responses.Results: Adverse events were mild except at the highest dose. Volunteers shed the organism an average of 5.1 days (range 0-13 days). Eighty-three percent (15/18) of subjects had a mucosal immune response to Salmonella LPS and flagella by IgA ELISPOT assay. Seventy-two percent (13/18) of subjects seroconverted to Salmonella antigens. No volunteer had a response to recombinant Gag as measured by serology, IgA ELISPOT, or immediate ex vivo gamma-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving >= 5 x 10(8) CFU had a response to HIV peptides in a cultured gamma-interferon ELISPOT assay.Conclusions: Although immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development. (c) 2006 Elsevier Ltd. All rights reserved.