Comparative immunologic effectiveness of variants of the DTP vaccine

The immunological effectiveness of two batches of adsorbed DPT vaccine, the batch with the normal content of antigens (control) and the batch with the content of diphtheria and tetanus toxoids reduced to 20 Lf/ml and 5 BU/ml respectively (test batch), has been studied under the conditions of controlled trial. As a result, the reduction of the antigenic content of adsorbed DPT vaccine has been found to exert no negative influence on the immunological effectiveness of the diphtheria, tetanus, and pertussis components of this preparation under the conditions of the new immunization schedule.     

Reactogenic properties of a DTP vaccine with a reduced antigen dosage

The reactogenic properties of batches of adsorbed DPT vaccine with the normal content of antigens and with the content of diphtheria and tetanus toxoids reduced, respectively, to 10 Lf and 5 BU per immunization dose have been studied under the conditions of a controlled epidemiological trial. The reduced antigenic content of adsorbed DPT vaccine decreased the number of vaccinal reactions 1.8 times, as well as the intensity of their manifestations.     

Comparative study of the antigenic activity and allergic transformation of the body in human revaccination with different doses of a chemical brucellosis vaccine

The study of different doses of chemical brucellosis vaccine (0.5 mg, 0.75 mg and 1 mg), used for the booster immunization of persons who had received primary immunization with chemical and live brucellosis vaccines, revealed that the characteristics of its antigenic potency were somewhat higher after primary immunization with the live vaccine. When used for booster immunization, the tested doses showed no differences in their antigenic potency irrespective of prior immunizations received by the immunized persons. In booster immunization chemical brucellosis vaccine was found to have poorly pronounced allergenic properties irrespective of its booster dose with the tendency towards greater sensitization to brucellosis allergen in persons primarily immunized with the live vaccine. When considering the possibility of using brucellosis chemical vaccine in medical practice, the complex evaluation of the characteristics showing its reactogenicity and antigenic potency, as well as the allergic transformation of the body induced by the injection of the vaccine, was carried out, which made it possible to recommend 1 mg of the vaccine as the optimal booster dose.     

Comparative study of the safety and reactogenicity of different doses of brucellosis chemical vaccine in human revaccination

The period of 11-12 months has been found to be the optimal interval, among other experimentally tested periods of time, between primary immunization and booster immunization with chemical brucellosis vaccine. The safety and low reactogenicity of different doses (1 mg, 0.75 mg and 0.5 mg) of the vaccine have been established. The occurrence and intensity of local and systemic reactions to this vaccine depend neither on the dose of the preparation, nor on previous immunization.     

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.     

Effect of repeat dose of BCG vaccination on humoral response in mice model

BCG is the only vaccine presently available against tuberculosis but it is estimated to prevent only 5% of the all potentially vaccine-preventable deaths due to Tuberculosis. Keeping these in view the present study has been undertaken to evaluate the efficacy of BCG and the effect of repeat dose of BCG on antimycobacterial humoral response in mouse model. To improve BCG immunogenicity, specific anti-mycobacterial immune responses (anti-BCG titre and total IgG level) were evaluated in mouse model using boost immunization protocols with the BCG vaccine. Mice induced with a repeat dose of BCG showed an increased anti mycobacterial humoral response, which gradually declined few weeks after single dose of BCG administration. The results suggest improved efficacy of BCG vaccine by giving repeat dose of BCG that can enhance the level of immunoprotection against tuberculosis as opposed to a single BCG dose.     

A new rabies vaccine in public health practice in the USSR

A new antirabies vaccine prepared on the basis of virus grown in the ovine brain, purified from 85-90% of brain-tissue ballast substances and inactivated with beta-propilactone has been developed at the Moscow Research Institute of Viral preparations (USSR Acad. Med. Sci.). The preparation produces no neuro-allergenic effect in tests on guinea pigs. When injected to humans, the vaccine shows much lower reactogenicity than Fermi vaccine. High antigenic and immunogenic activity of the new vaccine has made it possible to work out a less intensive immunization schedule in comparison with that used for immunization with Fermi vaccine and nonconcentrated tissue-culture vaccine, viz. doses of 3 ml for 12 days or doses of 3 ml for 20 days with two booster immunizations. The preparation has been introduced into medical practice.     

Control of immunologically crossreactive leptospiral infection by administration of lipopolysaccharides from a nonpathogenic strain of Leptospira biflexa

In our previous paper (Matsuo, K., Isogai, E., and Araki, Y., Carbohydr. Res., 328: 517-524, 2000), antigenic polysaccharides obtained from the lipopolysaccharide (LPS) fraction of a nonpathogenic leptospira, Leptospira biflexa patoc Patoc I, are shown to be broadly crossreactable with most rabbit antisera elicited by immunization with various pathogenic leptospires. The result led us to test a protective effect of the same LPS in a hamster model system by heterologously challenging with a pathogenic leptospira, L. interrogans manilae UP-MMG. Firstly, a similarity in the antigenic epitopes of L. biflexa and L. interrogans was confirmed by the following assays. In the microscopic agglutination test (MAT), a hamster antiserum elicited by immunization with the L. biflexa-LPS preparation was shown to agglutinate cells of L. interrogans. Contrarily, in the enzyme-linked immunosorbent assay (ELISA), the L. biflexa-LPS preparation was shown to crossreact with a hamster antiserum elicited by immunization with whole cells of L. interrogans. These results suggest that the same or closely related antigens may be present on the cell surfaces of both L. biflexa patoc Patoc I and L. interrogans manilae UP-MMG. Furthermore, in a protective assay, the prior administration of a L. biflexa-LPS preparation resulted in raising a protective response in hamsters against challenge by L. interrogans without any side effect. The protective effect was strongly dependent on the dose amounts and/or administration times of L. biflexa-LPS. Thus, L. biflexa-LPS preparations can use as a potent vaccine against leptospirosis caused by various leptospires.     

Use of adsorbed diphtheria-tetanus (DT) toxoid containing different doses of antigens in booster immunizations of children

To decrease the antigenic load in booster immunizations of children against diphtheria and tetanus, the immunological effectiveness and reactogenicity of different doses of both antigens (i. e 1 Lf and 1 BU; 2.5 Lf and 2.5 BU; 5 Lf and 5 BU) were studied. The study revealed that all these doses of the preparation were practically nonreactogenic: the total of systemic reactions was 0.9%. The study of the immunological effectiveness of adsorbed DT toxoid with reduced antigen content revealed the advantage of the commercial dose of the preparation (5 Lf of diphtheria antigen and 5 BU of tetanus antigen) over such doses of diphtheria and tetanus antigens as, respectively, 1 Lf and 1 BU; 2.5 Lf and 2.5 BU. Still, this advantage disappeared as early as 6 months after booster immunization. The results of these investigations indicate that booster immunization of children aged 6 years and over may be made with lower doses of adsorbed DT toxoid with reduced antigen content.     

Influence of BCG vaccine strain on the immune response and protection against tuberculosis

The Bacille Calmette–Guérin (BCG) vaccine has been used for more than 80 years to protect against tuberculosis. Worldwide, over 90% of children are immunized with BCG, making it the most commonly administered vaccine, with more than 120 million doses used each year. Although new tuberculosis vaccines are under investigation, BCG will remain the cornerstone of the strategy to fight the worsening tuberculosis pandemic for the foreseeable future. The recent delineation of genetic differences between BCG vaccine strains has renewed interest in the influence of the vaccine strain on the protective efficacy against tuberculosis. This review critically examines the data from animal and human studies comparing BCG vaccine strains. Although there is good evidence to support the notion that the induced immune response and protection afforded against tuberculosis differs between BCG vaccine strains, currently, there are insufficient data to favour or recommend one particular strain. Identifying BCG strains with superior protection would have a dramatic effect on tuberculosis control at a population level: a small increment in protection provided by BCG immunization will prevent large numbers of cases of severe tuberculosis and deaths, particularly in children.     

Comparative study of the immunoglobulins and specific antibodies in the blood of rabbits immunized with ADTP vaccine and ADT-anatoxin with normal and reduced antigen contents

Adsorbed DPT vaccine and adsorbed DT toxoids with normal and reduced antigen content were used for the immunization of rabbits. The levels of IgM and IgG and the dynamics of antibodies to diphtheria and tetanus toxins and to Bordetella pertussis in the blood sera of the animals were studied in the postvaccinal period (on days 15 and 34). This study revealed that the reduction of the antigen content of adsorbed DT toxoid to 5 Lf of diphtheria toxoid and 5 binding units of tetanus toxoid did not decrease the capacity of the preparation for increasing the levels of IgG and IgM, antibodies to diphtheria and tetanus toxins in the sera of the rabbits. The reduced content of these toxoids in adsorbed DPT vaccine did not affect its capacity for inducing the enhanced synthesis of IgG, antibodies to diphtheria and tetanus toxins, while the production of IgM and IgA remained unchanged. At the same time an increase in the titers of antibodies to B. pertussis in the animals was less pronounced than that observed after the injection of commercial adsorbed DPT vaccine. Additional investigations are necessary in order to establish the protective potency of the pertussis component in adsorbed DPT vaccine with the reduced content of toxoids and to find out the optimum antigenic composition for this preparation.     

Determination of the optimal inoculation dose of Brucella chemical vaccine

Brucellosis chemical vaccine, when injected intramuscularly, proved to be low-reactogenic, postvaccinal reactions, both systemic and local, becoming less frequent and intense with the decrease of the dose from 2 to 0.5 mg. The highest antigenic and immunogenic activity was observed with a dose of 1 mg; out of 4 tested doses this dose produced the highest percentage of seroconversions, the highest titers of agglutinins and the longest time of their persistence in the subjects. When introduced in doses of up to 2 mg, brucellosis chemical vaccine did not induce pronounced sensitization. A high degree of correlation between the indices of seroconversion frequency in Wright's agglutination test and Huddleson's test was established after vaccination with all tested doses. This fact indicates that one of these tests can be used for the assessment of the antigenic and immunogenic activity of the vaccine at an early period after immunization (the term of observation not exceeding 3 months). On the basis of the complex comparison of the indices characterizing the reactogenicity and the antigenic and immunogenic activity of 4 tested doses of brucellosis chemical vaccine a dose of 1 mg was chosen as the optimum vaccination dose.     

Vaccine prophylaxis in elderly patients

In 1997-1999 observation was made on elderly people living in old people's homes and in families, as well as groups of young males living in hostel-type homes, altogether 4,518 subjects. Standard inactivated whole-virion influenza vaccine was introduced in a dose of 0.5 ml subcutaneously in a single injection or intranasally in two administrations. In control groups placebo was used. The frequency of seroconversions to vaccine strains of influenza viruses was significantly less in elderly people than in young people following both subcutaneous and intranasal immunization (on the average, by 15-20%). In young people the prophylactic effectiveness of the vaccine introduced intranasally was the same as after subcutaneous immunization with the effectiveness index (EI) being equal to 2.1-2.8. In elderly people the effectiveness of the vaccine after subcutaneous immunization was the same as in young people (EI = 1.7-2.7), but insufficient after intranasal immunization (EI < or = 1.6). The preparation "Amber elixir plus" enhanced the effectiveness of immunization against influenza in elderly people.     

Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein

Key Ags of Mycobacterium tuberculosis initially identified in the context of host responses in healthy purified protein derivative-positive donors and infected C57BL/6 mice were prioritized for the development of a subunit vaccine against tuberculosis. Our lead construct, Mtb72F, codes for a 72-kDa polyprotein genetically linked in tandem in the linear order Mtb32(C)-Mtb39-Mtb32(N). Immunization of C57BL/6 mice with Mtb72F DNA resulted in the generation of IFN-gamma responses directed against the first two components of the polyprotein and a strong CD8(+) T cell response directed exclusively against Mtb32(C). In contrast, immunization of mice with Mtb72F protein formulated in the adjuvant AS02A resulted in the elicitation of a moderate IFN-gamma response and a weak CD8(+) T cell response to Mtb32c. However, immunization with a formulation of Mtb72F protein in AS01B adjuvant generated a comprehensive and robust immune response, resulting in the elicitation of strong IFN-gamma and Ab responses encompassing all three components of the polyprotein vaccine and a strong CD8(+) response directed against the same Mtb32(C) epitope identified by DNA immunization. All three forms of Mtb72F immunization resulted in the protection of C57BL/6 mice against aerosol challenge with a virulent strain of M. tuberculosis. Most importantly, immunization of guinea pigs with Mtb72F, delivered either as DNA or as a rAg-based vaccine, resulted in prolonged survival (>1 year) after aerosol challenge with virulent M. tuberculosis comparable to bacillus Calmette-Guérin immunization. Mtb72F in AS02A formulation is currently in phase I clinical trial, making it the first recombinant tuberculosis vaccine to be tested in humans.     

Current Status of Measles and Oral Poliovirus Vaccines

Live attenuated measles vaccine, accompanied by a dose of gamma globulin to reduce systemic reactions, has given a high degree of protection, probably long lasting. Further attenuated vaccine gives promise of achieving the same result without the use of gamma globulin. Inactivated vaccine has not been shown to give durable immunity, but a schedule of killed vaccine followed by live vaccine has provided protection with minimal reactions. Inactivated vaccine can probably be combined with other antigens.Sabin oral poliovirus vaccines of all three types have been highly effective in preventing paralytic illness and reducing the spread of virulent strains. Because of the rare occurrence, chiefly in adults, of paralytic cases considered to be probably vaccine-associated, though no proof was possible, it has been recommended in Canada that initial immunization with Salk vaccine be continued and that all infants and children should subsequently receive trivalent Sabin vaccine.     

Immunological effectiveness of secondary revaccination against tetanus performed at prolonged intervals

After primary immunization with adsorbed DPT vaccine antitetanus immunity was retained for 9-10 years in 90.6-98.4% of children covered by this study. The second booster immunization of children against tetanus with adsorbed DT toxoid with reduced antigen content, made at an interval prolonged to 7-10 years under the conditions of lower antitoxic immunity, ensured a high level of intense antitetanus immunity. These data point to the possibility of prolonging the interval between booster immunizations to 9-10 years and reducing the number of injections and antigenic load.     

Comparison of different delivery systems of DNA vaccination for the induction of protection against tuberculosis in mice and guinea pigs

The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs.     

Immunologic properties of purified and complex preparations of group-B meningococcal polysaccharide

The complex preparations of group B meningococcal polysaccharide have been found to be capable of inducing primary immune response in mice, while purified group B polysaccharide has proved to be immunologically inert. As revealed in this investigation, the intravenous injection to mice of the optimum doses of the complex preparation of group B polysaccharide leads to the increased number of specific B-antibody-forming cells in their spleens and to a rise in B-antibody titers in their sera; besides, the time course of the process has been studied. Both preparations have been found capable of forming the immunological memory in mice if booster immunization is made with the complex preparation of group B polysaccharide. The immunological inertness of purified group B polysaccharide is attributed, supposedly, to the action of some specific suppressor mechanism. Considering the pronounced antigenic activity of the complex preparation of group B polysaccharide and the insignificant admixture of endotoxin in this preparation, the suitability of its future use as vaccine for the prophylaxis of meningitis caused by group B meningococcus is indicated and the tentative immunization schedules are discussed.     

Cross-protection among lethal H5N2 influenza viruses induced by DNA vaccine to the hemagglutinin.

Inoculation of mice with hemagglutinin (HA)-expressing DNA affords reliable protection against lethal influenza virus infection, while in chickens the same strategy has yielded variable results. Here we show that gene gun delivery of DNA encoding an H5 HA protein confers complete immune protection to chickens challenged with lethal H5 viruses. In tests of the influence of promoter selection on vaccine efficacy, close correlations were obtained between immune responses and the dose of DNA administered, whether a cytomegalovirus (CMV) immediate-early promoter or a chicken beta-actin promoter was used. Perhaps most important, the HA-DNA vaccine conferred 95% cross-protection against challenge with lethal antigenic variants that differed from the primary antigen by 11 to 13% (HA1 amino acid sequence homology). Overall, the high levels of protection seen with gene gun delivery of HA-DNA were as good as, if not better than, those achieved with a conventional whole-virus vaccine, with fewer instances of morbidity and death. The absence of detectable antibody titers after primary immunization, together with the rapid appearance of high titers immediately after challenge, implicates efficient B-cell priming as the principal mechanism of DNA-mediated immune protection. Our results suggest that the efficacy of HA-DNA influenza virus vaccine in mice extends to chickens and probably to other avian species as well. Indeed, the H5 preparation we describe offers an attractive means to protect the domestic poultry industry in the United States from lethal H5N2 viruses, which continue to circulate in Mexico.     

HBsAg阴性母亲及其婴儿乙肝疫苗接种情况和免疫效果研究

目的：了解乙肝表面抗原阴性（HBsAg阴性）母亲及其婴儿乙肝疫苗接种情况及抗-HBs滴度水平,从而为今后针对该特殊人群进行更好的乙肝疫苗免疫策略提供依据。方法：2010年5月～2010年10月,对陕西省227对HBsAg阴性母亲及其婴幼儿（月龄为8～24月）进行流行病学调查并采集血液标本,对母婴血清抗-HBs进行定性及定量检测。结果：母亲乙肝表面抗体（抗-HBs）阳性率为45.4%,抗-HBs平均滴度为12.88 mIU/mL（95%CI：8.91-18.19）。婴儿乙肝疫苗首针、第二针和第三针的及时接种率分别为95.2%,93.8%和85.9%。婴儿抗-HBs阳性率为77.1%,抗-HBs平均滴度为37.15 mIU/mL（95%CI：28.18-48.98）。结论：婴儿乙肝疫苗首针及时接种率较高,但三针全程及时接种率仍需提高。母亲抗-HBs阳性率较低,应当重视HBsAg阴性孕龄妇女的乙肝疫苗接种及乙肝标志物的检测,从而提高该人群的乙肝免疫水平。