M.V. Sergeeva*, PhD, leading researcher in the laboratory of vector vaccines, https://orcid.org/0000-0003-0411-9896
A.A. Pulkina, researcher in the laboratory of vector vaccines, https://orcid.org/0000-0001-8609-8093
A.A. Shtro, PhD, head of the laboratory of chemotherapy for viral infections, https://orcid.org/0000-0002-2295-1881
K.A. Vasiliev, PhD, researcher in the laboratory of vector vaccines, https://orcid.org/0000-0002-7750-9652
E.A. Romanovskaya-Romanko, PhD, senior researcher in the laboratory of vector vaccines, https://orcid.org/0000-0001-7560-398X
A.V. Garshinina, researcher in the laboratory of chemotherapy for viral infections, https://orcid.org/0000-0002-6202-808X
A.V. Galochkina, PhD, leading researcher in the laboratory of chemotherapy for viral infections, https://orcid.org/0000-0002-3208-8006
A.A. Muzhikyan, PhD, leading researcher in the laboratory of vector vaccines, https://orcid.org/0000-0002-7093-0014
J.V. Buzitskaya, PhD, researcher in the laboratory of vector vaccines, https://orcid.org/0000-0002-8394-102X
M.A. Stukova, PhD, head of the laboratory of vector vaccines, https://orcid.org/0000-0002-2127-3820
Federal State Budgetary Institution “Influenza Research Institute named after A.A. Smorodintsev” of the Ministry of Health of Russia,
197376, Russia, Saint-Petersburg, Prof.Popova str., 15/17.
* Е-mail: [email protected]
respiratory syncytial virus
RSV infection animal model
vaccine associated enhanced respiratory disease
The study was carried out under the state contract No. 0373100122120000007 with the Federal State Budgetary Institution “TsSP” of the FMBA of Russia. The authors are grateful to the head of the vivarium, Krylova V.I. and employees of the vivarium of the Federal State Budgetary Institution “Influenza Research Institute named after A.A. Smorodintsev” of the Ministry of Health of Russia for assistance in providing special conditions for keeping animals.
Sergeeva M.V., Pulkina A.A., Shtro A.A., Vasiliev K.A., Romanovskaya-Romanko E.A., Garshinina A.V., Galochkina A.V., Muzhikyan A.A., Buzitskaya J.V., Stukova M.A. Implementation experience of cotton rat model for respiratory syncytial virus infection and immunopathology. Laboratory Animals for Science. 2022; 4. https://doi.org/10.57034/2618723X-2022-04-06
Cotton rats are widely used worldwide as an animal model in research of vaccines and chemotherapy against respiratory syncytial virus infection. The demand for this model is due to the fact that cotton rats are more susceptible to the RSV infection than laboratory mouse strains, and also carry a functional set of genes encoding Mx1 and Mx2 proteins, which are the most important components of the innate human antiviral defense system. Despite their small size, cotton rats are difficult to handle and manipulate, since they have retained the behavioral reactions of wild animals, avoid contact, and move quickly. In the present manuscript, we discuss the barriers to implementing the cotton rat model into laboratory research and present our experience.
The longest stage of the process was the time spent on negotiations with animal nursery and preparation of documents for receiving animals. Upon arrival, cotton rats (females, 6–8 weeks old) were housed in a separate vivarium room in individual cages equipped with sterilized bedding. The animals quickly adapted to the new conditions and began to steadily gain weight from the first day of the quarantine period. To simulate RSV infection, we used two infectious doses of the virus, 5 lg or 6 lg PFU/animal. Animals were injected with the virus intranasally without anesthesia or under inhalation anesthesia (a mixture of isoflurane and propylene glycol). Infection without the use of anesthesia was asymptomatic, regardless of the virus dose, although it was accompanied by productive virus replication, mainly in the upper respiratory tract. At the same time, infection of animals under anesthesia led to active replication of the virus in the lungs, and also significant loss of body weight and lung damage of animals infected with a high virus dose. Immunization of cotton rats with formalin inactivated RSV resulted in the appearance of classical markers of enhanced respiratory pathology in histological sections of the lungs and a decrease in animal weight. The results obtained make it possible to use the developed model of cotton rats to study the protective properties and safety of vaccines against RSV infection.
Conflict of interest
The authors declare no conflict of interest.
M.V. Sergeeva — сoncept and design of experiments, data visualization and preparation of the text of the manuscript, сritical analysis of the results obtained.
A.A. Shtro — сoncept and design of experiments.
M.A. Stukova — сoncept and вesign of уxperiments, manuscript editing.
A.A. Pulkina — cultivation and titration of viruses, interpretation of results.
K.A. Vasiliev — manipulations with animals, collection of primary data.
E.A. Romanovskaya-Romanko — cultivation and titration of viruses, interpretation of results.
A.V. Garshinina — manipulations with animals, collection of primary data.
A.V. Galochkina — manipulations with animals, collection of primary data.
A.A. Muzhikyan — histological analysis.
Zh.V. Buzitskaya — editing the manuscript.
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