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. 2014 Aug 7;8(8):e2969.
doi: 10.1371/journal.pntd.0002969. eCollection 2014 Aug.

A novel live-attenuated vaccine candidate for mayaro Fever

Affiliations

A novel live-attenuated vaccine candidate for mayaro Fever

William J Weise et al. PLoS Negl Trop Dis. .

Abstract

Mayaro virus (MAYV) is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

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Conflict of interest statement

I have read the journal's policy and have the following conflicts: SCW holds a patent for the attenuation methods used to make the vaccine described in this paper. This does not alter our adherence to all PLOS policies on sharing data and materials.

Figures

Figure 1
Figure 1. Genetic characteristics of MAYV vaccine strain.
A. Wild-type genome including subgenomic promoter; B. Vaccine strain with inactivated subgenomic promoter; C. Subgenomic promoter sequence (red lettering) with synonymous mutations indicated by lower-case letters. The deduced amino acid sequence is shown between the nucleotide sequences.
Figure 2
Figure 2. Replication kinetics of MAYV/IRES and wt MAYV after infection of A) Vero or B) MRC-5 cells at a multiplicity of infection (MOI) of 0.1 PFU/cell.
n = 3. * = p<0.05. Error bars indicate standard deviations.
Figure 3
Figure 3. Infection of 28-day-old CD1 mice with 105 PFU of MAYV/IRES or wt MAYV.
A) percent change in body weight, B) viremia, and C). PRNT80 titers for each cohort. * = p<0.05. Error bars indicate standard deviations.
Figure 4
Figure 4. Infection of A129 mice with 104 PFU of MAYV/IRES or wt MAYV.
A) percent survival, B) percent change in body weight, C) Footpad swelling, and D) viremia for each cohort. * = p<0.05. Error bars indicate standard deviations.
Figure 5
Figure 5. Response to challenge of MAYV/IRES-vaccinated A129 mice.
A) percent survival, B) percent change in body weight, and C) viremia for each cohort following challenge. Error bars indicate standard deviations.

References

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