[Results of preclinical study of inactivated subunit adsorbed monovalent influenza vaccine "PANDEFLU"].

AIM: To perform preclinical study of subunit monovalent adsorbed inactivated influenza vaccine "PANDEFLU" [strains A/California/7/2009 (HIN1)v]. MATERIALS AND METHODS: Preclinical study of acute toxicity on experimental animals (assessment of vaccine's toxic effects on organs and body systems; pathomorphologic study of organs and tissues after administration of the vaccine; assessment of its influence on hematologic indicators). RESULTS: It was shown that administration of the vaccine did not lead to death of animals as well as to decrease of body mass or development of pathologic, focal sclerotic changes in parenchymal cells and visceral stroma; the vaccine did not negatively change hematologic and biochemical indicators of blood. Results of necropsy and histological study after acute administration of the vaccine in standard dose did not lead to irritation, inflammation or destruction of tissues in the place of inoculation. The vaccine was apyrogenic and did not have local irritating and allergenic effects. Status of animals after acute inoculation of the vaccine demonstrated its good tolerability and safety in doses exceeding standard human doses more than tenfold. CONCLUSION. Performed research demonstrated absence of contraindications for conduction of clinical trials of "PANDEFLU" vaccine on limited contingent of volunteers.

[Study of tolerability and reactogenicity of pandemic vaccines against influenza type A/H1N1].

AIM: To study tolerability and safety of pandemic vaccines against influenza A/H1N1 "INFLUVIR" and "PANDEFLU" on limited group of volunteers during phase I clinical trial. MATERIALS AND METHODS: Thirty healthy volunteers were participated in phase I clinical trial. Clinical and laboratory tests of volunteers randomized to 2 groups (20 persons received vaccine and 10 persons - placebo) were performed. "INFLUVIR" vaccine was administered by intranasal route. Volunteers were hospitalized and followed up for development of local and systemic adverse events during 7 days after vaccination. "PANDEFLU" was administered intramuscularly; vaccinees were followed for 7 days in outpatient settings. RESULTS. Phase I clinical trial showed good tolerability and low reactogenicity of "INFLUVIR" and "PANDEFLU" vaccines. There were no moderate and severe local and systemic adverse events registered. CONCLUSION: On the basis of performed phase I clinical trial, phase II trial was recommended to perform in order to assess the reactogenicity, safety and immunogenicity of studied vaccines.

[Results of preclinical studies of live monovalent influenza vaccine Influvir].

AIM: To perform preclinical assessment of new live monovalent vaccine Influvir against pandemic influenza virus A/H1N1 [strainA/17/California/2009/38 (H1N1)]. MATERIALS AND METHODS: Preclinical studies of acute toxicity and effect of Influvir vaccine on systems and organs of laboratory animals (rats and outbred white mice) was performed according to modern requirements of Institute of Toxicology. RESULTS: According to results of toxicometry and necroscopy, live monovalent influenza vaccine Influvir during intransal application was safe and had good tolerability during 14 days of observation for experimental animals after acute application. Performed preclinical studies allow to label the studied vaccine as class V virtually nontoxic drugs. CONCLUSION: According to results of preclinical studies, clinical trials of live monovalent intranasal influenza vaccine Influvir can be permitted.

[Clinical trial of new inactivated influenza vaccine "Grifor"].

AIM: To confirm and prove on the extended contingent of volunteers the non-reactogenicity, safety and immunogenicity of "Grifor" vaccine in comparative trial with registered in Russia commercial vaccine "Vaxigrip". MATERIALS AND METHODS: Phase II clinical trial was performed on the research bases of Mechnikov Institute of Vaccines and Sera and Institute of Influenza. In single-blind comparative prospective randomized trial 300 adult volunteers (150 volunteers on each base) aged 18 - 60 y.o. were divided on 3 equivalent groups. Assessment of antigenic characteristics of "Grifor" vaccine was performed using hemagglutination inhibition assay (HAI) with chicken erythrocytes measuring geometric mean titer (GMT), seroconversion factor as well as level of seroconversion and seroprotection. RESULTS: Previously performed studies proved non-reactogenicity, safety and high immunogenicity of "Grifor", whereas this comparative trial performed with commercial vaccine "Vaxigrip" did not reveal significant advantage in any of studied vaccine. CONCLUSION: "Grifor" vaccine meet the requirements of both EMEA CPMP and methodic guidelines MY 3.3.2. 1758-03 for inactivated influenza vaccines, which allows to register vaccine "Grifor" in Russian Federation.

[Development and preclinical study of new generation virosomal split influenza vaccine "Grifor"].

New Russian virosomal split vaccine against influenza "Grifor" was developed. The vaccine is represented by mix of highly purified protective external and internal antigens of influenza A (H1N1 and H3N2) and B viruses. Developed technology of manufacture allowed to provide presentation of external antigens of influenza virus in the form of virosomes, and presentation of internal antigens in the form of micelles with maximal preservation of their antigenic activity. Using electron microscopy, electrophoresis in 10% polyacrilamide gel with sodium dodecyl sulfate, and polymerase chain reaction, morphologic and biochemical properties of the vaccine were studied. Preclinical study, including assessment of antigenic characteristics of "Grifor" vaccine compared to vaccine "Vaxigrip" (France), was performed. It was established that administration of the vaccine did not result in death of experimental animals, decrease of body mass, development of pathologic (including inflammatory, dystrophic and necrobiotic) changes in viscera or render adverse effects on blood hematologic and biochemical parameters and on the immune system. The vaccine was not pyrogenic and allergenic, did not have local irritating effects. Obtained results supported the appropriateness of conducting the clinical trials of "Grifor" vaccine on limited number of volunteers.

[Study of reactogenicity, safety and immunogenicity of inactivated virosomal split influenza vaccine "Grifor" during phase I clinical trial].

Phase I clinical trial of inactivated virosomal split influenza vaccine "Grifor" was conducted in the Mechnikov Research Institute of Vaccines and Sera as accredited base for such trials. Forty healthy volunteers (males and females) aged 18 - 50 years consented to participate in the trial. Reactogenicity, safety, and immunogenicity of new Russian influenza vaccine were assessed. Analysis of obtained results showed that there was evidence of safety and low reactogenicity of the vaccine as well as of its high immunogenic characteristics, which satisfied both the EMEA's Committee for Proprietal Medicinal Products criteria and requirements of Federal Service for Surveillance for Protection of Consumers Rights and Human Welfare (MU 3.3.2.1758-03) for inactivated influenza vaccines.