Reactogenicity and antigenic activity of a chromatographic cultured purified and concentrated inactivated dried vaccine against tick-borne encephalitis

The study of the characteristics of a new dried tissue-culture purified concentrated inactivated vaccine against tick-borne encephalitis, manufactured in the USSR, has revealed that the preparation is moderately reactogenic and produces no definite side effects in the vaccinees. In the process of the controlled epidemiological trial the optimum vaccination schedule for the primary immunization of adults against tick-borne encephalitis with the new preparation has been determined by the study of serum samples from the vaccinees in the hemagglutination inhibition test and the neutralization test in tissue culture. In accordance with this vaccination schedule the course of primary immunization with the chromatographic variant of the concentrated vaccine consists of two injections in a dose of 0.5 ml, made at an interval of 6 months.     

森林脑炎灭活疫苗加强免疫效果及免疫持久性观察

目的评价森林脑炎灭活疫苗加强免疫效果以及免疫持久性。方法采用单中心无对照设计,在吉林省选择571名≥8岁受试者进行疫苗基础免疫,其中400名受试者进行加强免疫,加强免疫后选择54名进行免疫持久性研究。于基础免疫前及免疫后1、6和12个月分别采血,加强免疫前及免疫后1、6、12、18、24、30、36和42个月分别采血检测抗体浓度,计算抗体阳性率和抗体几何平均浓度(geometric mean concentration, GMC)。结果基础免疫后1、6和12个月,抗体阳性率分别为96.05%、86.45%、76.95%,GMC值分别为753、332和225 VIEU/mL。加强免疫后1、6和12个月,抗体阳性率分别为95.87%、94.33%、91.54%,GMC值分别为3 391、2 322和1 981 VIEU/mL。加强免疫后42个月GMC值为747 VIEU/mL。结论森林脑炎疫苗加强免疫后具有良好的免疫持久性,与基础免疫相比,加强免疫具有更好的免疫应答。     

Preparation of a purified, inactivated Japanese encephalitis (JE) virus vaccine in Vero cells

An attenuated Japanese encephalitis (JE) virus SA14-14-2 (PDK) was adapted to Vero cells, a continuous cell line that has been licensed for human vaccine production, by serial passages. The resulting virus was purified by tangential flow ultrafiltration followed by sucrose density gradient ultracentrifugation, giving 2.3 mg purified virus per liter of culture supernatant. Treatment with 0.05% formalin for 4 days at 22 °C completely inactivated viral infectivity while preserving its antigenicity. The purified, inactivated JE virus was formulated with alum hydroxide and administered to mice by intraperitoneal route. In terms of its ability to induce anti-JE neutralizing antibody and to protect the immunized animal against neurovirulent virus challenge, the purified, inactivated JE virus formulated with alum was equivalent to the exiting commercial mouse brain-derived vaccine (JE-VAX, Aventis Pasteur Inc.).     

A cultured concentrated inactivated vaccine against tick-borne encephalitis studied during the immunization of children and adolescents

The word deals with the results obtained in the study of the reactogenicity and immunological activity of concentrated and inactivated tissue-culture tick-borne encephalitis vaccine, manufactured by the Chumakov Institute of Poliomyelitis and Viral Encephalitides, in the immunization of children and adolescents. The vaccine proved to be moderately reactogenic and exhibited pronounced immunological activity. In 91.5% of the immunized children the fourfold increase of the antibody level was observed. On the basis of the data obtained in this study the tick-borne encephalitis vaccine was recommended for use in medical practice for the prophylaxis of tick-borne encephalitis among children and adolescents.     

A comparison of the immune response induced by DNA or by an inactivated vaccine against tick-borne encephalitis

BALB/c mice were immunized with recombinant plasmid DNA pSVK3-ENS1 and pcDNAI-NS3 containing, respectively, genes E-NS1 and NS3 of tick-borne encephalitis (TBE) virus. Antibodies to TBE virus proteins were detected in the blood sera of the immunized animals by the method of the enzyme immunoassay. Though the titers of virus-specific antibodies in the sera of mice immunized with protein vaccines exceeded those registered after immunization with DNA vaccines, essential protective immunity was observed after the use of both vaccines.     

Evaluation of mouse brain-derived, inactivated Japanese encephalitis vaccine

Japanese encephalitis (JE) is a serious encephalitis caused by JE virus. Approximately 20% of JE patients die and 50% patients recover with neuro-psychiatric sequelae. In Japan, the number of JE patients was over 1000 per year in 1960s; however, the number decreased dramatically and has been less than 10 since 1990. Ministry of Health, Labour and Welfare suspended the strong recommendation for vaccination with the mouse brain-derived JE vaccine, because of cases who developed acute disseminated encephalomyelitis (ADEM) after vaccination with JE vaccine. However, it has not been fully confirmed on scientific bases that ADEM was caused by mouse brain-derived JE vaccine. Tissue culture derived-JE vaccine is under development. It is expected that this new vaccine will come to the market soon and that the recommendation of universal vaccination with JE vaccine will be implemented at the earliest occasion.     

ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy

The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live- attenuated vaccine developed with this technology has successfully undergone phase I and II clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WN(02) vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans.     

Antigenic activity of a gamma-ray inactivated, concentrated, purified cultured antirabies vaccine]

Concentrated purified cultural rabies vaccine inactivated with gamma-rays caused in intramuscular injection (2 ml twice at an interval of 23 and 21 days) production of virus-neutralizing antibodies both in experiments on animals and in the vaccinated volunteers in titres not below those obtained in persons given a complete course of cultural rabies vaccine inoculations. No untoward reactions occurred.     

Synthesis, immunogenicity and antigenic characteristics of the glycoprotein E fragments from the tick-borne encephalitis virus]

Six peptide fragments of the envelope protein E of the tick-borne encephalitis virus involving the predicted T-helper epitopes were synthesized. Their ability to induce antibodies without conjugation with any high-molecular-mass carrier was studied in mice of three lines. Five of six synthesized peptides exhibited immunogenic properties, which differed in dependence on the haplotype of immunized mice. The peptide binding to the antiviral antibodies was studied, and two peptides were revealed that demonstrated a high ability to recognize the viral antibodies in the horse and human sera. These peptides are promising for the development of diagnostic agents for the tick-borne encephalitis virus.     

Age affects quantity but not quality of antibody responses after vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis

The impairment of immune functions in the elderly (immunosenescence) results in post-vaccination antibody titers that are significantly lower than in young individuals. It is, however, a controversial question whether also the quality of antibodies declines with age. In this study, we have therefore investigated the age-dependence of functional characteristics of antibody responses induced by vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis (TBE). For this purpose, we quantified TBE virus-specific IgG and neutralizing antibody titers in post-vaccination sera from groups of young and elderly healthy adults and determined antibody avidities and NT/ELISA titer ratios (functional activity). In contrast to the quantitative impairment of antibody production in the elderly, we found no age-related differences in the avidity and functional activity of antibodies induced by vaccination, which also appeared to be independent of the age at primary immunization. There was no correlation between antibody avidity and NT/ELISA ratios suggesting that additional factors affect the quality of polyclonal responses, independent of age. Our work indicates that healthy elderly people are able to produce antibodies in response to vaccination with similar avidity and functional activity as young individuals, albeit at lower titers.     

Investigation of luromarin efficacy on mice with experimental tick-borne encephalitis

Oral use of Luromarin, extracted from sea algae Zostera asiatica, was efficient in protection of mice from lethal infection induced by highly pathogenic strain of TBE virus, by extending their average lifespan. Luromarin demonstrated potentiating action in combination with ribavirin and cycloferon.     

An assessment of the immunoepidemiological efficacy of a liquid cultured killed vaccine against tick-borne encephalitis virus strain 205 in the Maritime Territory]

Inactivated vaccine against tick-borne encephalitis (TBE), prepared on the basis of strain 205, is characterized by epidemiological (53%) and immunobiological activity. The appearance of a few TBE cases among the vaccinees is probably due to different maturation rate of immune response to various strains (different specificity of immune response). A suggestion has been made that no inactivated vaccine prepared from a single strain can produce a reliable protective effect because of pronounced heterogeneity of the population of TBE virus.     

Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice

The potential use of variola virus, the etiological agent of smallpox, as a bioterror agent has heightened the interest in the reinitiation of smallpox vaccination. However, the currently licensed Dryvax vaccine, despite its documented efficacy in eradicating smallpox, is not optimal for the vaccination of contemporary populations with large numbers of individuals with immunodeficiencies because of severe adverse effects that can occur in such individuals. Therefore, the development of safer smallpox vaccines that can match the immunogenicity and efficacy of Dryvax for the vaccination of contemporary populations remains a priority. Using the Wyeth strain of vaccinia virus derived from the Dryvax vaccine, we generated a recombinant Wyeth interleukin-15 (IL-15) with integrated IL-15, a cytokine with potent immunostimulatory functions. The integration of IL-15 into the Wyeth strain resulted in a >1,000-fold reduction in lethality of vaccinated athymic nude mice and induced severalfold-higher cellular and humoral immune responses in wild-type mice that persisted longer than those induced by the parental Wyeth strain. The superior efficacy of Wyeth IL-15 was further demonstrated by the ability of vaccinated mice to fully survive a lethal intranasal challenge of virulent vaccinia virus even 10 months after vaccination, whereas all mice vaccinated with parental Wyeth strain succumbed. By integrating IL-15 into modified vaccinia virus Ankara (MVA), a virus currently under consideration as a substitute for the Dryvax vaccine, we developed a second vaccine candidate (MVA IL-15) with greater immunogenicity and efficacy than Dryvax. Thus, Wyeth IL-15 and MVA IL-15 viruses hold promise as more-efficacious and safe alternatives to the Dryvax vaccine.     

Return of inactivated whole-virus vaccine for superior efficacy

The swine, influenza, H1N1 outbreak in 2009 highlighted the inadequacy of the currently used antibody-based vaccine strategies as a preventive measure for combating influenza pandemics. The ultimate goal for successful control of newly arising influenza outbreaks is to design a single-shot vaccine that will provide long-lasting immunity against all strains of influenza A virus. A large amount of data from animal studies has indicated that the cross-reactive cytotoxic T (Tc) cell response against conserved influenza virus epitopes may be the key immune response needed for a universal influenza vaccine. However, decades of research have shown that the development of safe T-cell-based vaccines for influenza is not an easy task. Here, I discuss the overlooked but potentially highly advantageous inactivation method, namely, γ-ray irradiation, as a mean to reach the Holy Grail of influenza vaccinology.     

国产甲型肝炎灭活疫苗用于儿童免疫效果研究

为了探讨国产甲型肝炎灭活疫苗在儿童中应用的免疫效果,选择2～15岁抗-HAV阴性健康易感儿童91名作为接种对象,采用0、6程序接种国产甲型肝炎灭活疫苗250U／剂,观察免疫后的局部反应和全身反应,并于全程免疫后一个月检测抗-HAV阳转率和抗体GMT。结果91例观察对象在初免和加强免疫后均未见即时副反应,只在8～72小时内出现轻微的一过性局部和全身反应。全程免疫后一个月抗-HAV阳转率为100％。抗体GMT为14 407mIU／ml。国产甲肝灭活疫苗在儿童中应用具有良好的安全性和免疫原性,采用0、6个月程序可获得高滴度抗体。     

The efficacy of vaccination and serotherapy in tick-borne encephalitis in the Maritime Territory

The use of different vaccines manufactured in the USSR under the condition of the Far East has revealed that killed vaccines do not produce a protective effect, sufficient for the prophylaxis of tick-borne encephalitis (TBE). This is probably due to the circulation of a highly virulent population of TBE virus at the Territory. This virus population may produce a severe course of infection and aggravate the clinico-epidemiological characteristics of the effectiveness of vaccines. Besides, low levels of specific and nonspecific humoral resistance factors in the residents of the Far East, especially in spring and summer, contribute to this fact. The negative effect of specific serotherapy for persons over 40 years of age has been established.     

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。