Whitehead Stephen S, Falgout Barry, Hanley Kathryn A, Blaney Joseph E, Markoff Lewis, Murphy Brian R
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Virol. 2003 Jan;77(2):1653-7. doi: 10.1128/jvi.77.2.1653-1657.2003.
The Delta30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN1Delta30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4Delta30 vaccine candidate. rDEN1Delta30 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN1Delta30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1Delta30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the Delta30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the Delta30 mutation into wt DEN viruses belonging to each of the four serotypes.
Delta30缺失突变最初是通过从登革热病毒4型（DEN4）的3'非翻译区（3'UTR）去除核苷酸172至143而产生的，随后被引入野生型（wt）登革热病毒1型（DEN1）的同源区域。由此产生的病毒rDEN1Delta30在恒河猴体内减毒至与rDEN4Delta30候选疫苗相似的水平。rDEN1Delta30在恒河猴体内的减毒程度比先前描述的候选疫苗rDEN1mutF更高，rDEN1mutF在3'UTR中也含有突变，并且这两种疫苗对野生型DEN1的攻击均具有高度保护作用。rDEN1Delta30和rDEN1mutF在HuH-7-SCID小鼠体内也均表现出减毒。然而，在胸腔接种后，rDEN1Delta30和rDEN1mutF在华丽巨蚊（Toxorhynchites splendens）体内均未表现出复制受限。Delta30突变使DEN1和DEN4病毒均减毒的能力表明，通过将Delta30突变引入属于四种血清型的野生型DEN病毒中，可以制备出一种四价DEN疫苗。
