
携带有基孔肯亚病毒的蚊子(图)
基孔肯亚热是一种少见的病毒性传染病。临床表现主要有三:发热病人常突然起病,寒战、发热,体温可达39℃,伴有头痛、恶心、呕吐、食欲减退,淋巴结肿大。一般发热1~7天即可退热,约3天后再次出现较轻微发热(医学上把这种发热称为双峰热),持续3~5天恢复正常。皮疹80%的患者在发病后2~5天,可在躯干、四肢的伸展侧、手掌和足底出现红色斑丘疹或猩红热样皮疹,有瘙痒感,数天后可消退。有些患者可有结膜充血和轻度畏光的结膜炎表现。关节疼痛与发热同时,患者全身的多个关节和脊椎出现十分剧烈的疼痛,且病情发展迅速,往往在数分钟或数小时内关节功能丧失,不能活动。恢复期长达几周至数月,甚至3年以上。基孔肯雅热的病死率不高,除少数老年患者因身体衰弱而死亡外,成人感染者几乎没有死亡。尽管绝大多数病人的关节损害最终可以恢复,但剧烈疼痛和恢复缓慢的特点可明显影响人的正常生活和工作。
这种由蚊子携带的病原体在印度、亚洲和非洲的东南部有数百万人受到感染。
最近,科学家们研发出一种新的疫苗用于抵御基孔肯亚病毒感染。该研究的论文发表在最新一期的《PLoS Pathogens》杂志上。
在实验中,由来自美国德克萨斯州大学,威斯康星州和阿拉巴马州的科学家们共同研发完了这种试验性疫苗,其一支剂量就能有效保护小鼠不受该病毒的感染。
论文的通讯作者,德克萨斯州大学医学院人类传染和免疫部门的主任Scott Weaver说道:“目前,我们仍然没有任何批准可以在临床上用于治疗基孔肯亚病毒感染的方法和疫苗,因此研发该疫苗非常重要。”
这种试验性疫苗是一种“减毒活体疫苗”,它通过使用基因修饰手段对基孔肯亚病毒进行改造。这种经过改造后成为的疫苗和野生型的基孔肯亚病毒有两方面的不同:第一,它不会导致任何疾病;第二;它也不会被蚊子携带。
这种活体病毒疫苗在大量生产时也相对廉价—这对于遭受严重病毒感染但资源有限的地区来说非常重要。Weaver说道:“我们需要阻止这种病毒在印度和亚洲东南部的蔓延,不仅仅只是为了保护那里的人不受感染,也要在当一位病毒携带者到来时,降低引起该地区疾病爆发的风险。而最好的办法就是使用这种疫苗,所以我们得考虑这种疫苗将在哪里进行使用且在资金上他们能否负担得起。”(生物探索 Jun译)
生物探索推荐英文论文原文摘要:
Novel Chikungunya Vaccine Candidate with an IRES-Based Attenuation and Host Range Alteration Mechanism.
Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES) from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus.
