Vindurampulle Christofer J, Cuberos Lilian F, Barry Eileen M, Pasetti Marcela F, Levine Myron M
Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
Vaccine. 2004 Sep 9;22(27-28):3744-50. doi: 10.1016/j.vaccine.2004.03.025.
This study investigated the utility of attenuated Salmonella enterica serovar Typhi strain CVD 908-htrA (908 h) in a heterologous prime-boost strategy. Mice primed intranasally (i.n.) with 908 h expressing fragment C (Frag C) of tetanus toxin and boosted intramuscularly (i.m.) with tetanus toxoid (TT) mounted enhanced and accelerated serum IgG anti-Frag C responses in comparison to unprimed, vector-primed and homologously-primed and boosted mice. Serum antitoxin responses were also determined; mice that were vaccinated following a heterologous prime-boost regimen exhibited the highest levels of Frag C-specific toxin neutralizing antibodies 1 week after boosting. Mice primed and boosted i.m. with TT developed a significantly greater proportion of serum IgG1 antibodies and weaker IFN-gamma levels in contrast to those primed intranasally (i.n.) with rS. Typhi that were homologously or heterologously boosted. These encouraging pre-clinical data provide a rational basis for undertaking a pilot clinical trial to evaluate this strategy. An ability to stimulate enhanced, accelerated responses to parenteral vaccination following mucosal priming may be advantageous in the immunoprophylaxis of many infectious diseases, including those of biodefense importance.
本研究调查了减毒伤寒沙门氏菌血清型 Typhi 菌株 CVD 908-htrA（908 h）在异源初免-加强策略中的效用。与未初免、载体初免、同源初免和加强的小鼠相比，经鼻内（i.n.）用表达破伤风毒素片段 C（Frag C）的 908 h 初免并经肌肉内（i.m.）用破伤风类毒素（TT）加强的小鼠产生了增强且加速的血清 IgG 抗 Frag C 反应。还测定了血清抗毒素反应；按照异源初免-加强方案接种疫苗的小鼠在加强后 1 周表现出最高水平的 Frag C 特异性毒素中和抗体。与经鼻内（i.n.）用鼠伤寒沙门氏菌初免并同源或异源加强的小鼠相比，经 TT 肌肉内初免和加强的小鼠产生的血清 IgG1 抗体比例显著更高，而 IFN-γ 水平更低。这些令人鼓舞的临床前数据为开展一项试点临床试验以评估该策略提供了合理依据。粘膜初免后能够刺激对肠外疫苗接种产生增强、加速的反应，这在许多传染病的免疫预防中可能具有优势，包括那些具有生物防御重要性的传染病。
