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Handling of the Cotton Rat in Studies for the Pre-clinical Evaluation of Oncolytic Viruses
Published on: November 24, 2014
Use of cotton rats for preclinical evaluation of measles vaccines
P R Wyde1, K J Stittelaar, A D Osterhaus
1Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. pwyde@bcm.tmc.edu
Abstract:
The continued prevalence and medical impact of measles worldwide has created interest in the development of new generations of measles vaccines. Monkeys can be used for preclinical testing of these vaccines. However, a more practical and less expensive animal model is highly desirable, particularly for initial vaccine development and evaluation. Cotton rats have been shown to support the replication of different strains of measles virus (MV), and thus may be useful for these purposes. To test this concept, the immunogenicity and protective efficacy of two standard (Moraten and trivalent measles, mumps, rubella) and four experimental (two recombinant ALVAC, one ISCOM subunit and live attenuated Edmonston-Zagreb) MV vaccines were evaluated in naïve cotton rats, and cotton rats with passively acquired MV-specific neutralizing serum antibodies. All of the test vaccines were immunogenic and protected naíve animals from pulmonary infection and viral dissemination. However, under the conditions utilized, only the Edmonston-Zagreb vaccine provided such protection to animals with significant levels of passively acquired MV-specific neutralizing antibodies. The results of these tests and the potential of using cotton rats as an animal model for preliminary testing of MV vaccines are discussed.
Insights
Cotton rats show promise as a cost-effective animal model for measles vaccine development. While most vaccines protected naive rats, only the Edmonston-Zagreb vaccine offered protection against measles virus in rats with pre-existing antibodies.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Measles remains a significant global health concern, driving the need for novel vaccine strategies.
- Current preclinical vaccine testing often relies on non-human primates, which are expensive and less practical.
- Cotton rats have demonstrated susceptibility to measles virus (MV) replication, suggesting their potential as an alternative animal model.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of various measles virus vaccines in cotton rats.
- To assess the utility of cotton rats as a model for initial measles vaccine development and evaluation.
- To determine if cotton rats with passively acquired immunity can be protected by measles vaccines.
Main Methods:
- Tested six measles virus vaccines (two standard, four experimental) in cotton rats.
- Vaccines were administered to both naive cotton rats and those with passively acquired MV-specific neutralizing antibodies.
- Evaluated vaccine immunogenicity, protection against pulmonary infection, and viral dissemination.
Main Results:
- All tested measles virus vaccines were immunogenic in naive cotton rats.
- All vaccines protected naive cotton rats from pulmonary infection and viral spread.
- Only the Edmonston-Zagreb vaccine conferred protection in cotton rats with significant levels of passively acquired MV-specific neutralizing antibodies.
Conclusions:
- Cotton rats are a viable model for evaluating measles virus vaccine immunogenicity and efficacy in naive animals.
- The Edmonston-Zagreb vaccine demonstrated superior efficacy in the presence of pre-existing measles immunity in cotton rats.
- Cotton rats offer a practical and cost-effective alternative for preliminary preclinical testing of measles vaccines.

