Limits...
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 FP swelling in C57BL/6J and RAG1-/- mice following FP infection with either PBS or 3 log10 PFU of wt CHIKV.There was a biphasic pattern of inflammation seen in C57BL/6, but not RAG1-/- mice. Error bars represent one standard deviation. *denotes statistical significance (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482609&req=5

pntd.0003800.g003: Percent change in FP swelling in C57BL/6J and RAG1-/- mice following FP infection with either PBS or 3 log10 PFU of wt CHIKV.There was a biphasic pattern of inflammation seen in C57BL/6, but not RAG1-/- mice. Error bars represent one standard deviation. *denotes statistical significance (p<0.05).

Mentions: Following FP inoculation with wt CHIKV, C57BL/6J mice developed a biphasic pattern of inflammation at the injection site that was not observed with RAG1-/- mice (Fig 3). C57BL/6J and RAG1-/- animals showed some footpad swelling on day 2 post-inoculation, which decreased to baseline levels by day 3. C57BL/6J mice inoculated with wt CHIKV showed increased swelling at day 6, peaking at day 7, and resolving by day 10 post-inoculation. In contrast, RAG1-/- mice never showed footpad swelling after day 3, and similarly, mice inoculated with vaccine strain CHIKV/IRES never exhibited footpad swelling.


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 FP swelling in C57BL/6J and RAG1-/- mice following FP infection with either PBS or 3 log10 PFU of wt CHIKV.There was a biphasic pattern of inflammation seen in C57BL/6, but not RAG1-/- mice. Error bars represent one standard deviation. *denotes statistical significance (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003800.g003: Percent change in FP swelling in C57BL/6J and RAG1-/- mice following FP infection with either PBS or 3 log10 PFU of wt CHIKV.There was a biphasic pattern of inflammation seen in C57BL/6, but not RAG1-/- mice. Error bars represent one standard deviation. *denotes statistical significance (p<0.05).
Mentions: Following FP inoculation with wt CHIKV, C57BL/6J mice developed a biphasic pattern of inflammation at the injection site that was not observed with RAG1-/- mice (Fig 3). C57BL/6J and RAG1-/- animals showed some footpad swelling on day 2 post-inoculation, which decreased to baseline levels by day 3. C57BL/6J mice inoculated with wt CHIKV showed increased swelling at day 6, peaking at day 7, and resolving by day 10 post-inoculation. In contrast, RAG1-/- mice never showed footpad swelling after day 3, and similarly, mice inoculated with vaccine strain CHIKV/IRES never exhibited footpad swelling.

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