final program.qxd - Parallels Plesk Panel

FP 1.10
Replication-Competent Platforms for Lassa Fever Vaccine Design
Lukashevich IS 1 , Moshkoff D 1 , Patterson J 2 , Carrion R 2 , Bredenbeek P 3 , Spaan WJM 3 ,
Salvato MS 1
1
Institute of Human Virology, University of Maryland, Baltimore, MD, USA;
2
Southwest Foundation for Biomedical Research, San Antonio, TX, USA;
3
Leiden University Medical Center, Leiden, The Netherlands
Objectives
Lassa (LAS) fever is a serious medical problem in West Africa. The sizeable disease
burden and the possibility that LAS virus can be used as an agent of biological warfare
make a strong case for vaccine development. Replication-competent vaccines elicit strong
cellular immune responses, confer long-term protection after a single injection, and have
low manufacturing costs. These features make live vaccines are very attractive
alternatives for African countries.
Methods
1. Reassortant technology was used to make reassortants between LAS and Mopeia
(MOP) virus, a non-pathogenic close relative of LAS. Clone ML29, selected from a library
of MOP/LAS reassortants, encodes the major antigens (NP and GPC) of LAS and the
replication machinery of MOP. 2. The full-length infectious cDNA clone of the vaccine
strain of Yellow Fever (17D) has been used to design the second vaccine candidate,
recombinant YF17D/LAS-GPC. LAS GPC gene was cloned and expressed in frame
between E and NS1 genes of YF17D.
Results
1. Replication of ML29 was attenuated in guinea pigs and nonhuman primates. The ML29-
vaccinated animals were fully protected not only against challenge with homologous virus,
LAS-JOS, but also against distantly-related LAS-NIG isolate. Simultaneous replication of
ML29 and LAS in vaccinated/challenged animals attenuated wild-type LAS infection.
2. The recombinant YF17D/LAS-GPC replicated poorly in guinea pigs but still elicited
specific antibodies against LAS and YF17D antigens. A single vaccination with the
recombinant virus protected 80% guinea pigs against heterologous challenge.
Conclusion
Both viruses, clone ML29 and recombinant YF17D/LAS-GPC, are promising vaccine
candidates for LAS fever.
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