Comprehensive Preclinical Evaluation of the VLP Vaccine “Gam-VLP-rota” Following Single-Dose Administration: Hematology, Biochemistry, and Histopathology in Sprague–Dawley Rats (Part II)
Abstract
Background. Rotavirus infection remains a major cause of severe gastroenteritis in children worldwide. Virus-like particle (VLP)-based vaccines are considered a promising non-replicating alternative to live vaccines due to their favorable safety profile.
Objective. To evaluate the acute toxicity of the VLP-based vaccine “Gam-VLP-rota” following single intramuscular administration in Sprague–Dawley (SD) rats.
Materials and Methods. Male and female SD rats were allocated into four experimental groups (vehicle control; 30, 120, and 600 µg antigen per animal; n = 14 per sex per group). The vaccine was administered once into the quadriceps femoris muscle (0.2 mL per animal). Animals were euthanized either 24 h after administration (Day 2) or after a 14-day recovery period (Day 15). Clinical condition, body weight, and food consumption were monitored. Hemostasis parameters, hematology, serum biochemistry, bone marrow cellular composition, organ weights, necropsy findings, histopathology, and local tolerability were evaluated.
Results. No mortality or severe clinical manifestations were observed. On Day 2, transient intergroup differences in body weight gain and moderate reduction in food intake were detected in animals receiving the highest antigen dose (600 µg). These parameters normalized by Days 7–15. Reversible changes in hemostasis were recorded, including prolonged prothrombin time and elevated fibrinogen levels. Hematological analysis on Day 2 demonstrated dose-dependent neutrophilia accompanied by relative lymphopenia with absolute lymphocytosis; hematological and myelogram parameters returned to baseline by Day 15. In serum biochemistry, animals receiving 600 µg antigen showed increased total protein and globulin levels in both sexes, along with decreased ALT and alkaline phosphatase activity in males; these differences resolved by Day 15. No pathological alterations were detected macroscopically or microscopically in examined organs. Reactive enlargement of inguinal lymph nodes without signs of inflammation was observed. No local irritative effects were identified.
Conclusion. Single intramuscular administration of the VLP-based vaccine “Gam-VLP-rota” at a dose of 600 µg antigen per animal (approximately 20× the anticipated clinical dose) demonstrated a favorable safety profile in an acute toxicity model.
Keywords: rotavirus; virus-like particles; preclinical toxicology; hematology; serum biochemistry; histopathology; Sprague–Dawley rats; vaccine safety.
Keywords:
rotavirus, Virus-Like Particles, preclinical toxicology, hematology, serum biochemistry, Histopathology, Sprague–Dawley rats, vaccine safetyDOI
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Copyright (c) 2026 Oleg V. Ledenev , Ludmila V. Kostina , Olesya V. Eliseeva , Oleg E. Latyshev , Maria M. Silaenkova, Igor A. Dyachenko , Gulsara A. Slashcheva , Elvira R. Shaykhutdinova , Ekaterina N. Kazakova , Elena S. Sadovnikova , Olga I. Patsap , Arkady N. Murashev , Tatiana V. Grebennikova
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