Mucosal Immunization with Attenuated Salmonella enterica Serovar Typhi Expressing Protective Antigen of Anthrax Toxin (PA83) Primes Monkeys for Accelerated Serum Antibody Responses to Parenteral PA83 Vaccine

被引：27

作者：

Galen, James E. ^{[1
,2
]}

Chinchilla, Magaly ^{[1
,2
]}

Pasetti, Marcela F. ^{[1
,3
]}

Wang, Jin Yuan ^{[1
,2
]}

Zhao, Licheng ^{[1
,2
]}

Arciniega-Martinez, Ivonne ^{[1
,3
]}

Silverman, David J. ^{[4
]}

Levine, Myron M. ^{[1
,2
,3
]}

机构：

[1] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA

[2] Univ Maryland, Sch Med, Dept Med, Div Geog Med, Baltimore, MD 21201 USA

[3] Univ Maryland, Sch Med, Dept Pediat, Div Infect Dis & Trop Pediat, Baltimore, MD 21201 USA

[4] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2009年 / 199卷 / 03期

关键词：

IMMUNE-RESPONSES; ADSORBED AVA; INHALATIONAL ANTHRAX; IMMUNOGENICITY; PROGRAM; CORRELATE; EFFICACY; STRAIN; SAFETY; ADULTS;

D O I：

10.1086/596066

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Salmonella enterica serovar Typhi vaccine strain CVD 908-htrA was genetically engineered for stable plasmid-based expression of protective antigen of anthrax toxin (PA83) fused with the export protein ClyA (ClyA-PA83). The priming potential of CVD 908-htrA expressing ClyA-PA83 was assessed in 12 rhesus and 20 cynomolgus macaques that were immunized mucosally (i.e., intranasally) on days 0 and 14. A parenteral booster with purified PA83 plus alum was given to rhesus macaques on days 42 and 225; cynomolgus monkeys received a booster with either PA or licensed anthrax vaccine (BioThrax; Emergent Biosolutions) only one time, 3 months after priming. Monkeys primed with S. Typhi expressing ClyA-PA83 developed high levels of serum toxin-neutralization activity (TNA) antibodies (50% effective dose [ED50], > 1.3 x 10(3)), 7 days after receipt of the booster, whereas unprimed controls lacked serum TNA(ED50, 0). In nonhuman primates, the success of this anthrax vaccine strategy based on heterologous mucosal priming followed by a parenteral subunit vaccine booster paves the way for clinical trials.

引用

页码：326 / 335

页数：10