Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons

被引:65
|
作者
Wald, Anna [1 ]
Koelle, David M. [2 ]
Fife, Kenneth
Warren, Terri [3 ]
LeClair, Kenneth [4 ]
Chicz, Roman M. [4 ]
Monks, Stephen [4 ]
Levey, Daniel L. [4 ]
Musselli, Cristina [4 ]
Srivastava, Pramod K. [5 ]
机构
[1] Univ Washington, Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Dept Med Epidemiol & Lab Med, Seattle, WA 98195 USA
[2] Fred Hutchinson Canc Res Ctr, Dept Med Lab Med & Global Hlth Med, Seattle, WA 98104 USA
[3] Westover Hts Clin, Portland, OR USA
[4] Agenus Inc, Lexington, MA USA
[5] Univ Connecticut, Sch Med, Farmington, CT USA
关键词
Heat shock protein; CD8(+) T cell; Genital herpes; Therapeutic vaccine; HERPES-SIMPLEX-VIRUS; CYTOTOXIC T-LYMPHOCYTE; RECURRENT GENITAL HERPES; HEAT-SHOCK PROTEINS; GLYCOPROTEIN-D; ANTIGEN PRESENTATION; CONFERS PROTECTION; PERIPHERAL-BLOOD; CONTROLLED-TRIAL; SENSORY GANGLIA;
D O I
10.1016/j.vaccine.2011.09.046
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
HSV-2, the primary causative agent of genital herpes, establishes latency in sensory ganglia and reactivates causing recurrent lesions and viral shedding. Induction or expansion of CD4(+) and CD8(+) T cell responses are expected to be important for a successful therapeutic vaccine against HSV-2. A candidate vaccine consisting of 32 synthetic 35mer HSV-2 peptides non-covalently complexed with recombinant human Hsc70 protein (named HerpV, formerly AG-707) was tested for safety and immunogenicity in a Phase I study. These peptides are derived from 22 HSV-2 proteins representative of all phases of viral replication. Thirty-five HSV-2 infected participants were randomized and treated in one of four groups: HerpV+QS-21 (saponin adjuvant), HerpV. QS-21, or vehicle. The vaccine was well tolerated and safe. All seven participants with evaluable samples who were administered HerpV with QS-21 demonstrated a statistically significant CD4(+) T cell response to HSV-2 antigens, and the majority of such participants demonstrated a statistically significant CD8(+) T cell response as well. To our knowledge, this is the first candidate vaccine against HSV-2 to demonstrate a broad CD4(+) and CD8(+) T cell response in HSV-2(+) participants, and the first HSP-based vaccine to show immune responses against viral antigens in humans. (C) 2011 Elsevier Ltd. All rights reserved.
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页码:8520 / 8529
页数:10
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