Comparative evaluation of the reactogenicity and antigenic activity of Soviet inactivated influenza vaccines

The reactogenicity and antigenic potency of existing inactivated influenza vaccines were tested on 750 practically healthy adults. In all the preparations under test the levels of reactogenicity were found to correspond to the Technical Specifications TY--KBC, but the subunit type vaccine, "Gripovac", proved to possess the lowest reactogenicity and was, therefore, recommended for further trials in young children. Taking into account the characteristics of antigenic potency, the work gives grounds for the necessity of increasing the content of hemagglutinin in the vaccine prepared by the centrifugal method and for the practical use of the same volumetric dose (0.2 ml) for both virion vaccines (prepared by the centrifugal and chromatographic methods).     

Comparative study of the reactogenicity and immunogenicity of new Soviet and commercial vaccines for preventing Japanese encephalitis

In this article the results of testing Soviet vaccines for the prophylaxis of Japanese encephalitis, cell-culture inactivated adsorbed liquid vaccine and brain-tissue purified dried vaccine, are generalized and the comparison of their reactogenicity and immunogenicity characteristics with those of a similar commercial preparation manufactured by Toshiba Kagaku Kogyo Co., Ltd. (Japan) is made. Cell-culture inactivated liquid vaccine has proved to be the optimal preparation: it produces the most prolonged and intensive immunity and, when introduced by two methods, shows low reactogenicity.     

Development of mucosal influenza inactivated vaccines

In this review recent data on the development of mucosal influenza inactivated vaccines with the use of mucosoadhesive adjuvants are presented. After the intranasal administration of such vaccines the formation of not only systemic, but also local immunity (IgA antibodies), as well as cross protection against the variants of influenza virus within its serotype, can be observed. Some mucosal influenza vaccines have passed clinical tests. Certain drawbacks of Escherichia thermolabile enterotoxin, used as mucosoadhesive adjuvant, and difficulties which may arise in mass immunization with mucosal vaccines due to the necessity of introducing them in two or three intranasal administrations are indicated.     

Free haemagglutinin in inactivated whole virus influenza vaccines

While studying the haemagglutinin content of whole virus inactivated influenza vaccines by the single radial diffusion test and quantitative electron microscopy, it was found that not all haemagglutinin measured by single radial diffusion was bound to virions, a part of it being in a free state. The influence of unbound haemagglutinin on the immunogenicity of whole virus inactivated influenza vaccine is discussed. In addition, the use of single radial diffusion for the assessment of unbound haemagglutinin is suggested.     

Adjuvanted vaccines against influenza in the elderly

Influenza is an important public health issue,especially with the aging of the population,since the most serious consequences of the illness affect the elderly.Between 1979 and 2001,approximately 41000...     

Assessment of the effectiveness of inactivated influenza vaccines for adults

In 9 controlled epidemiological observations (1977-1984) the effectiveness of modern Soviet whole-virion vaccines was studied in organized groups of adults and at industrial enterprises. During the epidemic outbreaks of influenza of different etiology and intensity morbidity rate in influenza and acute respiratory diseases was shown to decrease 1.1-2.2 times among the vaccinees, depending on the correspondence of epidemic and vaccine influenza strains. The absence of influenza virus B in inactivated influenza vaccines was the reason for their low effectiveness during influenza outbreaks of mixed etiology B + A (H1N1).     

Immunogenicity and reactogenicity of 2009 influenza A (H1N1) inactivated monovalent non-adjuvanted vaccine in elderly and immunocompromised patients

Background

Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them.

Methods

This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination.

Results

319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included.The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events.

Conclusions

The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01218685","term_id":"NCT01218685"}}NCT01218685)     

The evaluation of the reactogenicity and immunological activity of an inactivated 3-component influenza vaccine with an elevated hemagglutinin concentration in the inoculation dosage

In this work the reactogenic properties and antigenic potency of inactivated trivalent influenza vaccine, obtained by elution and centrifugation and containing up to 9-11 micrograms of hemagglutinin for influenza viruses A(H1N1) and A(H3N2) and up to 14 micrograms for influenza virus B, were studied. The reactogenicity of the preparation was found to correspond to the regulations. The immunogenic potency characteristics of individual batches of this trivaccine were higher than the immunogenicity of divaccines, but did not meet the requirements of technical specifications.     

The evaluation of the reactogenicity and immunogenic activity of a new concentrated inactivated leptospirosis vaccine

In the controlled field trial the reactogenicity, safety and antigenic activity of a new concentrated inactivated leptospirosis vaccine after its administration in one and two injections of 0.5 ml were studied in comparison with those of the existing commercial vaccine, introduced in two injections in doses of 2.0 and 2.5 ml. The new experimental vaccine exhibited low reactogenicity and was found to be safe and highly immunogenic when introduced in a single injection of 0.5 ml. As shown in this trial, the immunogenic characteristics of immunization made in a single injection were not inferior than those obtained as the result of immunization made in two injections, yielding high percentage of seroconversions (89.8% to 98.3%) with respect to 4 Leptospira serogroups and leading to the production of the protective titers of corresponding antibodies. The existing commercial vaccine was inferior to the experimental one in antigenic activity (the frequency of seroconversions, antibody titers). The results of the trial make it possible to recommend the experimental concentrated leptospirosis vaccine for use in medical practice in a dose of 0.5 ml introduced in a single injection.     

Recombinant trimeric HA protein immunogenicity of H5N1 avian influenza viruses and their combined use with inactivated or adenovirus vaccines

Background

The highly pathogenic avian influenza (HPAI) H5N1 virus continues to cause disease in poultry and humans. The hemagglutinin (HA) envelope protein is the primary target for subunit vaccine development.

Methodology/Principal Findings

We used baculovirus-insect cell expression to obtain trimeric recombinant HA (rHA) proteins from two HPAI H5N1 viruses. We investigated trimeric rHA protein immunogenicity in mice via immunizations, and found that the highest levels of neutralizing antibodies resulted from coupling with a PELC/CpG adjuvant. We also found that the combined use of trimeric rHA proteins with (a) an inactivated H5N1 vaccine virus, or (b) a recombinant adenovirus encoding full-length HA sequences for prime-boost immunization, further improved antibody responses against homologous and heterologous H5N1 virus strains. Data from cross-clade prime-boost immunization regimens indicate that sequential immunization with different clade HA antigens increased antibody responses in terms of total IgG level and neutralizing antibody titers.

Conclusion/Significance

Our findings suggest that the use of trimeric rHA in prime-boost vaccine regimens represents an alternative strategy for recombinant H5N1 vaccine development.     

The results of state trials of inactivated influenza vaccines for children

Controlled epidemiological surveillance covering the total number of 13,355 schoolchildren aged 11-14 years and adolescents was carried out with a view to compare the efficacies of inactivated influenza vaccines. The children were immunized intradermally in a single injection with inactivated influenza vaccines containing A (H3N2) and A (H1N1) hemagglutinins, 3.5 micrograms per 0.2 ml of the preparation each. The studies demonstrated the safety and low reactogenicity of these vaccines, as well as their high antigenic potency. In 1984 during mixed influenza B + A (H1N1) epidemic the preparations produced a pronounced prophylactic effect: the efficacy indices were 1.6-1.9 (p less than 0.001). The results obtained in these studies made it possible to recommend two inactivated influenza vaccines (chromatographic and centrifugal) for practical medicine with the aim of protecting children aged 11 years and over from influenza.     

轮状病毒四价灭活疫苗的制备及在小鼠的免疫原性研究

制备轮状病毒四价灭活疫苗,观察其在小鼠体内的抗体应答情况。实验采用轮状病毒原液经凝胶过滤层析纯化,灭活后配制四价疫苗,肌肉注射免疫小鼠,ELISA法测定小鼠血清IgA、IgG。将单价G1、G2、G3、G4型灭活病毒原液及四价轮状病毒灭活疫苗免疫小鼠后,均可刺激产生针对RV的高水平的特异性IgG抗体,但IgA应答较弱。表明四价轮状病毒灭活疫苗在小鼠中具备很好的免疫原性。     

Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations

In a strictly controlled epidemiological trial on 12,643 school children aged 11-14 years the reactogenic properties and safety of killed influenza chromatographic vaccine under the conditions of multiple immunization were studied. A single immunization dose of the vaccine (0.2 ml) contained the hemagglutinins of influenza viruses A/Philippines/82 (H3N3) and A/Kiev/59/79 (H1N1), 3.5 micrograms each. The preparation was introduced by means of a jet injector. The vaccine was shown to be clinically and immunologically safe under the conditions of the regular multiple immunization of children over the period of 4 years.     

Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines

The patterns of cellular immune responses induced by live attenuated influenza vaccine (LAIV) versus those of the trivalent inactivated influenza vaccine (TIV) have not been studied extensively, especially in children. The goals of this study were to evaluate the effects of TIV and LAIV immunization on cellular immunity to live influenza A virus in children and adults and to explore factors associated with variations in responses to influenza vaccines among individuals. A gamma interferon (IFN-gamma) flow cytometry assay was used to measure IFN-gamma-producing (IFN-gamma+) NK and T cells in peripheral blood mononuclear cell cultures stimulated with a live influenza A virus strain before and after LAIV or TIV immunization of children and adults. The mean percentages of influenza A virus-specific IFN-gamma+ CD4 and CD8 T cells increased significantly after LAIV, but not TIV, immunization in children aged 5 to 9 years. No increases in the mean levels of influenza A virus-reactive IFN-gamma+ T cells and NK cells were observed in adults given LAIV or TIV. TIV induced a significant increase in influenza A virus-reactive T cells in 6-month- to 4-year-old children; LAIV was not evaluated in this age group. The postvaccination changes (n-fold) in the percentages of influenza A virus-reactive IFN-gamma+ T and NK cells in adults were highly variable and correlated inversely with the prevaccination percentages, in particular with that of the CD56(dim) NK cell subset. In conclusion, our findings identify age, type of vaccine, and prevaccination levels of immune reactivity to influenza A virus as factors significantly associated with the magnitude of cellular immune responses to influenza vaccines.     

Comparative clinical trial of vaccines against avian influenza

Scientic-production association "Microgen" has finished 1st phase of clinical trials of candidate vaccines against avian influenza in order to assess their reactogenicity, safety, and immunogenicity. Two vaccines constructed from NIBRG-14 vaccine strain [A/Vietnam/1 194/2004 (H5N1)], obtained from World Health Organization, were studied: "OrniFlu" (inactivated subunit influenza vaccine adsorbed on aluminium hydroxide) and inactivated polymer-subunit influenza vaccine with polyoxydonium (IPSIV). Clinical trial of the vaccines with different quantity of antigen (15, 30, and 45 mcg of H5N1 virus hemagglutinin) was carried out in Influenza Research Institute (St. Petersburg) and in Mechnikov Research Institute of Vaccines and Sera (Moscow). Analysis of results allowed to conclude that both vaccines were safe, well tolerated and characterized by low reactogenicity. Two-doses vaccination schedule was needed to meet required seroconversion and seroprotection rates (> or =1:40 in > or =70% of vaccinated volunteers). "Orni-Flu" vaccine containing 15 mcg of hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) in one dose as well as IPSIV containing 45 mcg of hemagglutinin and 0.75 mg of polyoxydonium in one dose were most immunogenic after 2 doses - seroprotection rates in microneutralization assay were 72.2% and 77.0% respectively. Marked influence of aluminium hydroxide content on immunogenicity of the "OrniFlu" vaccine was confirmed in the study. Optimal quantity of adjuvant was 0.5 mg per dose. According to basic concept of vaccine development, preference is given to vaccine that under minimal quantity of antigen induces sufficient specific immune response and is safe in volunteers. "OrniFlu" vaccine containing 15 mcg of H5N1 virus hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) corresponded to these requirements that allowed researchers to recommend it for clinical trials of 2nd phase.     

Comparative evaluation on mouse nasal immunogenicity of arylmethane-, xanthene-, quinone-imine-, and acridine-dye-inactivated Sendai virus vaccines

Twenty-seven kinds of organic dye-inactivated Sendai virus vaccines were prepared by treatment in dark at 23 C for 2 months or more, and selected with the high HA titers as a guide. Their nasal immunogenicities were examined in mice by contact infection and immunofluorescent method, and the relative merits of the dye-inactivants were determined. The strongest protection was elicited with acriflavine-, auramine O-, eosin Y-, neutral red-, night blue-, patent blue V-, thymol blue-, uranin-, and xylene cyanol FF-treated vaccines. Middling protective efficacy was induced by use of erio green B-, malachite green-, methyl green-, proflavine-, pyronin B-, and thionin-inactivated vaccines. Dye-inactivated vaccines that resulted in the weakest protection were Bindschedler's green-, bromothymol blue-, erythrosin B-, ethyl violet-, gallein-, light green SF yellowish-, methyl violet-, new methylene blue N-, phenol red-, rhodamine 6G-, spirit blue- and victoria blue B-treated ones. Serum HI titers developed by nasal vaccination were variable, and rose still more in most vaccinated groups postexposure. Elicitation of the most effective nasal immunogenicity in dye-inactivated vaccines appeared to depend on selective modification of capsid protein or ribose in viral core with dyes possessing definite functions, despite the different molecular structures.