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A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.

Seymour RL, Adams AP, Leal G, Alcorn MD, Weaver SC - PLoS Negl Trop Dis (2015)

Bottom Line: In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development.To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model.Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

View Article: PubMed Central - PubMed

Affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.

ABSTRACT
Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

No MeSH data available.


Related in: MedlinePlus

Percent change in body weight in C57BL/6J and RAG1-/- mice after footpad inoculation with CHIKV/IRES or wt CHIKV (3 log10 PFU).There was weight loss (>3%) in RAG1-/- mice infected with wt CHIKV, which gradually improved, and there was mild weight loss (<2%) in C57BL/6J mice infected with wt CHIKV and in C57BL/6J mice infected with CHIKV/IRES, which also improved. There was no weight loss in RAG1-/- mice infected with CHIKV/IRES. For all mice, there were no clinical signs of illness (e.g., lethargy, ruffled fur) detected after infection. *denotes statistical significance (p<0.05).
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pntd.0003800.g001: Percent change in body weight in C57BL/6J and RAG1-/- mice after footpad inoculation with CHIKV/IRES or wt CHIKV (3 log10 PFU).There was weight loss (>3%) in RAG1-/- mice infected with wt CHIKV, which gradually improved, and there was mild weight loss (<2%) in C57BL/6J mice infected with wt CHIKV and in C57BL/6J mice infected with CHIKV/IRES, which also improved. There was no weight loss in RAG1-/- mice infected with CHIKV/IRES. For all mice, there were no clinical signs of illness (e.g., lethargy, ruffled fur) detected after infection. *denotes statistical significance (p<0.05).

Mentions: To determine the effects of wt CHIKV, CHIKV/IRES and CHIKV vaccine strain 181/25, mice were inoculated either SC or via the FP (each route 103 PFU). There were no clinical signs of illness (e.g., lethargy, ruffled fur) following SC or FP inoculation of RAG1-/- or congenic C57BL/6J mice with either vaccine strain or wt CHIKV, and no change in weight was identified after SC infection regardless of the virus strain (S1 Dataset). This was in contrast to RAG1-/- and C57BL/6J mice infected with wt CHIKV via the FP, which showed mild but significant weight loss compared to sham-infected controls (Fig 1). Vaccine strain 181/25 was not tested via the FP route.


A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.

Seymour RL, Adams AP, Leal G, Alcorn MD, Weaver SC - PLoS Negl Trop Dis (2015)

Percent change in body weight in C57BL/6J and RAG1-/- mice after footpad inoculation with CHIKV/IRES or wt CHIKV (3 log10 PFU).There was weight loss (>3%) in RAG1-/- mice infected with wt CHIKV, which gradually improved, and there was mild weight loss (<2%) in C57BL/6J mice infected with wt CHIKV and in C57BL/6J mice infected with CHIKV/IRES, which also improved. There was no weight loss in RAG1-/- mice infected with CHIKV/IRES. For all mice, there were no clinical signs of illness (e.g., lethargy, ruffled fur) detected after infection. *denotes statistical significance (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482609&req=5

pntd.0003800.g001: Percent change in body weight in C57BL/6J and RAG1-/- mice after footpad inoculation with CHIKV/IRES or wt CHIKV (3 log10 PFU).There was weight loss (>3%) in RAG1-/- mice infected with wt CHIKV, which gradually improved, and there was mild weight loss (<2%) in C57BL/6J mice infected with wt CHIKV and in C57BL/6J mice infected with CHIKV/IRES, which also improved. There was no weight loss in RAG1-/- mice infected with CHIKV/IRES. For all mice, there were no clinical signs of illness (e.g., lethargy, ruffled fur) detected after infection. *denotes statistical significance (p<0.05).
Mentions: To determine the effects of wt CHIKV, CHIKV/IRES and CHIKV vaccine strain 181/25, mice were inoculated either SC or via the FP (each route 103 PFU). There were no clinical signs of illness (e.g., lethargy, ruffled fur) following SC or FP inoculation of RAG1-/- or congenic C57BL/6J mice with either vaccine strain or wt CHIKV, and no change in weight was identified after SC infection regardless of the virus strain (S1 Dataset). This was in contrast to RAG1-/- and C57BL/6J mice infected with wt CHIKV via the FP, which showed mild but significant weight loss compared to sham-infected controls (Fig 1). Vaccine strain 181/25 was not tested via the FP route.

Bottom Line: In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development.To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model.Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

View Article: PubMed Central - PubMed

Affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.

ABSTRACT
Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

No MeSH data available.


Related in: MedlinePlus