Abstract:
INTRODUCTION:Chikungunya virus (CHIKV) is a re-emerging pathogen responsible for causing outbreaks of febrile disease accompanied with debilitating joint pain. Symptoms typically persist for two weeks, but more severe and chronic chikungunya illnesses have been reported, especially in the elderly. Currently, there are no licensed vaccines or antivirals against CHIKV available. In this study, we combined a CHIK virus-like particle (VLP) vaccine with different adjuvants to enhance immunogenicity and protection in both, adult and aged mice. METHODS:CHIK VLP-based vaccines were tested in 6-8-week-old (adult) and 18-24-month-old (aged) female C57BL/6J mice. Formulations contained CHIK VLP alone or adjuvants: QuilA, R848, or Imject Alum. Mice were vaccinated three times via intramuscular injections. CHIKV-specific antibody responses were characterized by IgG subclass using ELISA, and by microneutralization assays. In addition, CHIKV infections were characterized in vaccinated and non-vaccinated adult mice and compared to aged mice. RESULTS:In adult mice, CHIKV infection of the right hind foot induced significant swelling, which peaked by day 7 post-infection at approximately 170% of initial size. Viral titers peaked at 2.53 × 1010 CCID50/ml on day 2 post-infection. Mice vaccinated with CHIK VLP-based vaccines developed robust anti-CHIKV-specific IgG antibody responses that were capable of neutralizing CHIKV in vitro. CHIK VLP alone or CHIK plus QuilA administered by IM injections protected 100% of mice against CHIKV. In contrast, the antibody responses elicited by the VLP-based vaccines were attenuated in aged mice, with negligible neutralizing antibody titers detected. Unvaccinated, aged mice were resistant to CHIKV infection, while vaccination with CHIKV VLPs exacerbated disease. CONCLUSIONS:Unadjuvanted CHIK VLP vaccination elicits immune responses that protect 100% of adult mice against CHIKV infection. However, an improved vaccine/adjuvant combination is still necessary to enhance the protective immunity against CHIKV in the aged.
journal_name
PLoS Negl Trop Disjournal_title
PLoS neglected tropical diseasesauthors
Arévalo MT,Huang Y,Jones CA,Ross TMdoi
10.1371/journal.pntd.0007316subject
Has Abstractpub_date
2019-04-26 00:00:00pages
e0007316issue
4eissn
1935-2727issn
1935-2735pii
PNTD-D-18-01794journal_volume
13pub_type
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0001214
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Treponema pallidum infection evokes vigorous immune responses, resulting in tissue damage. Several studies have demonstrated that IL-17 may be involved in the pathogenesis of syphilis. However, the role of Th17 response in neurosyphilis remains unclear. METHODOLOGY/PRINCIPAL FINDINGS:In this study, Th17 in ...
journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章
doi:10.1371/journal.pntd.0003004
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abstract::The immunomodulatory properties of lipophosphoglycans (LPG) from New World species of Leishmania have been assessed in Leishmania infantum and Leishmania braziliensis, the causative agents of visceral and cutaneous leishmaniasis, respectively. This glycoconjugate is highly polymorphic among species with variation in s...
journal_title:PLoS neglected tropical diseases
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doi:10.1371/journal.pntd.0004848
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journal_title:PLoS neglected tropical diseases
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:PLoS neglected tropical diseases
pub_type: 杂志文章,随机对照试验
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