IMPROVING THE SAFETY OF VACCINE WITH OIL ADJUVANTS

  • Authors: Skupnevskii S.1, Pukhaeva E.2, Badtiev A.2, Rurua F.2, Batagova F.3, Farnieva Z.3
  • Affiliations:
    1. Laboratory of Subcellular Structures, Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of the Russian Academy of Sciences
    2. Laboratory of Subcellular Structures, Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of RAS
    3. Laboratory of Subcellular Structures, Postgraduate of the Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of RAS
  • Section: Статьи
  • URL: https://iimmun.ru/iimm/article/view/1897
  • DOI: https://doi.org/10.15789/2220-7619-ISO-1897

Cite item

Abstract

Reactogenicity of adjuvants is the main reason to limitation of increasing the effectiveness in vaccine therapy. The aim was to reduce the immunotoxic effects of complete Freund's adjuvant (CAF) in warm-blooded animals. Materials and methods. The object of study was Wistar-rat. Negative control (solvents); positive control (single subcutaneous injection CAF of 0.1 ml / 200 g body weight (b.w.)); experience "minimum" and "maximum" (per os administration of 1:4 citric and succinic acids in ratio of 17 and 88 mg/kg b.w. during 4 weeks after immunization of CAF). Body weight, hematological (complete blood count) and biochemical (hydroperoxides, malondialdehyde, catalase activity, dehydrogenase activity of mitochondria) parameters were studied in dynamics. At the end of the experiment, necropsy was performed and the relative mass coefficients of internal organs were calculated. The spleen and connective tissue (knee joint) were examined histologically. The median, C25–C75 quartiles, Mann-Whitney U-test were calculated.

Results and its discussion. For animals of negative control group, the studied parameters were within the norm. Immunization of warm-blooded with CAF was accompanied by the transition of an acute inflammatory reaction (3rd week) to a chronic one (7th week). The total number of leukocytes increased from 12.5∙109 (negative control) to 26.6∙109/L (P=0.01) on the 3rd week and then decreased to 19.2∙109/L (P=0.01) to the 7th. Platelets also increased statistical significant: from 506∙109 (negative control) to 656∙109/L (P=0.01, 3rd week) with a following decrease to 610∙109/L by the 7th week (P=0.01). Activation of lipid peroxidation was manifested by an increase of malondialdehyde (MDA) level by 55.8–61.8% (P=0.01); the general toxic effect of CAF resulted in 11.7% weight loss (P=0.01), swelling of the spleen and reduction of the thymus. Administration of antioxidant acids led to a dose-dependent decrease of inflammation (leukocytes at the minimum dosage are 19.6∙109–20.9∙109/L; at the maximum 16.6∙109–16.0∙109/L), as well as normalization of the "platelet/leukocyte" index to 29.5-36.3 (positive control 24.6, negative control 40.5). The protective effect of acids was also manifested as maintaining of body weight, activation of catalase and inhibition of lipid peroxidation. The therapeutic effect revealed in decrease of degenerative changes in spleen and connective tissue: reduce of hemorrhagic focuses, swelling and preservation of histoarchitectonics.

Conclusion. The use of citric and succinic acids contributes to a significant reduction in the toxicity of CAF due to increasing the total antioxidant status, inhibiting lipid peroxidation, improve mitochondrial metabolic activity, which ultimately leads to a decrease in general systemic inflammation and allows to recommend this acids as immunoprotectors of oil adjuvants.

About the authors

Sergeii Skupnevskii

Laboratory of Subcellular Structures, Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of the Russian Academy of Sciences

Email: dreammas@yandex.com
ORCID iD: 0000-0002-6233-5944
http://ibmi-osetia.ru/

Dr. Sci. (Biol.), Leading Researcher, Laboratory of Subcellular Structures, Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of the Russian Academy of Sciences

Russian Federation

Elena Pukhaeva

Laboratory of Subcellular Structures, Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of RAS

Author for correspondence.
Email: medgenetika435@yandex.ru
ORCID iD: 0000-0002-0850-2537
http://ibmi-osetia.ru/

Junior Researcher

Russian Federation

Alibec Badtiev

Laboratory of Subcellular Structures, Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of RAS

Email: medgenetika435@yandex.ru
ORCID iD: 0000-0001-5850-5173
http://ibmi-osetia.ru/

Senior Researcher

Russian Federation

Fatima Rurua

Laboratory of Subcellular Structures, Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of RAS

Email: medgenetika435@yandex.ru
ORCID iD: 0000-0001-9424-0467
http://ibmi-osetia.ru/

Junior Researcher

Russian Federation

Fatima Batagova

Laboratory of Subcellular Structures, Postgraduate of the Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of RAS

Email: medgenetika435@yandex.ru
ORCID iD: 0000-0001-9105-0350
http://ibmi-osetia.ru/

Junior Researcher

Russian Federation

Zhanna Farnieva

Laboratory of Subcellular Structures, Postgraduate of the Department of Molecular and Cellular Mechanisms of Autoimmune Diseases, Institute of Biomedical Research, Affiliate of Vladikavkaz Scientific Center of RAS

Email: medgenetika435@yandex.ru
ORCID iD: 0000-0002-9154-4729
http://ibmi-osetia.ru/

Junior Researcher

Russian Federation

References

  1. Козлов В.Г., Ожерелков С.В., Санин А.В., Кожевникова Т.Н. Адъюванты в современной медицине и ветеринарии // Журнал микробиологии, эпидемиологии и иммунобиологии. 2014. № 1. С. 91-102. Kozlov V.G., Ozherelkov S.V., Sanin A.V., Kozhevnikova T.N.
  2. Adjuvants in modern medicine and veterinary. Journal of microbiology, epidemiology and immunobiology. 2014,no. 1. pp. 91-102. URL: https://cyberleninka.ru/article/n/adyuvanty-v-sovremennoy-meditsine-i-veterinarii (дата обращения: 24.02.2022).(In Russ.)
  3. Методы клинических лабораторных исследований // Под ред. В.С. Камышникова. 8- е изд. М. : МЕДпресс-информ; 2016. 736 с. Methods of clinical laboratory research. Pod red. prof. V.S. Kamyshnikova. – 8- e izd. – M. : MEDpress-inform, 2016, 736 p. (In Russ.)
  4. Семакова А.П., Микшис Н.И. Адъювантные технологии в создании современных вакцин // Проблемы особо опасных инфекций. 2016. №2. С. 28-35. Semakova A.P., Mikshis N.I. Adjuvant technologies in the creation of modern vaccines. Problems of especially dangerous infections. 2016, no 2. pp. 28-35. doi: 10.21055/0370-1069-2016-2-28-35 (In Russ.)
  5. Справочник по лабораторным методам исследования. Под ред. Л. А. Даниловой. Москва: Питер; 2003. 733 с. Handbook of laboratory research methods. Pod red. L. A. Danilovoj. - Moskva : Piter, 2003, 733 p. (In Russ.)

Supplementary files

There are no supplementary files to display.


Copyright (c) Skupnevskii S., Pukhaeva E., Badtiev A., Rurua F., Batagova F., Farnieva Z.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies