Evaluation of the immunological effectiveness of the planned vaccinal prophylaxis of diphtheria and tetanus in Sverdlovsk and Sverdlovsk Province

The level and intensity of antitoxic immunity to diphtheria and tetanus in children and adolescents were determined. The presence of tetanus antitoxin in titers exceeding the protective level in 96.3-98.5% of the examined children and adolescents is indicative of a high actual coverage by immunization. Protective titers against diphtheria were lower. There was no essential difference in the levels of protection in children immunized according to the vaccination schedule and in those immunized with some deviations from this schedule. A considerable part of newborns and children aged 3 months had antibodies to diphtheria and tetanus antitoxins. After the third booster immunization changes in antidiphtheria immunity characteristics occurred only in 2.5% of the vaccines and no changes in antitetanus immunity characteristics were observed.     

Measles epidemic from failure to immunize.

During 1988 through 1990, California experienced its worst measles epidemic in more than a decade, with 16,400 reported cases, 3,390 hospital admissions, and 75 deaths. More than half of the patients were younger than 5 years; the highest incidence was among infants younger than 12 months. The epidemic centered in low-income Hispanic communities in southern and central California. The major cause of the epidemic was low immunization levels among preschool-aged children and young adults. Rates of complications, admission to hospital, and death were surprisingly high. Outbreak control efforts met with indeterminate success. Problems with these efforts included insufficient funding early in the epidemic and disappointing public response to community-based immunization campaigns. The cost of medical care and outbreak control for the epidemic is conservatively estimated at $30.9 million. Unless the level of immunization in preschool-aged children is increased, this type of epidemic will probably recur.     

Assessment of the prophylactic effectiveness of an inactivated influenza vaccine by immunizing schoolchildren in the springtime

To evaluate the prophylactic effectiveness of influenza inactivated chromatographic vaccine, limited epidemiological observations were made on school children aged 11-14 years in Leningrad, in the autumn of 1981 and the spring of 1982. For immunization, made in a single administration, the vaccine composed of A (H3N2) + +A (H1N1) and containing 3.0-3.4 micrograms of hemagglutinin of each component per 0.2 ml of the preparation was used. Altogether 6928 schoolchildren were under observation; of these, 3686 children were immunized and 3242 children received placebo. The results of questioning and the analysis of morbidity rate among the schoolchildren, both immunized and receiving placebo, showed the safety and low reactogenicity of the vaccine irrespective of the time of the immunization campaign. The immunogenic potency of the preparation, as indicated by all observation results, proved to be higher in spring, than in autumn. The data thus obtained indicate that children immunized in spring were better protected and retained a higher level of protection within 12 months after immunization. The shift of the time of the immunization campaign from autumn to spring increased the immune layer in the groups of children by 16.5%. In 10 months after spring immunization the morbidity rate in influenza and acute respiratory diseases among the vaccinees was found to decrease 1.7 times.     

Postinfection and postvaccinal antianthrax immunity in human subjects

Antibodies to Bacillus anthracis protective antigen (PA) and to the lethal factor (LF) of B. anthracis exotoxin in the blood sera of anthrax patients and of subjects with a history of the disease, as well as of persons immunized with STI live vaccine, were studied by the heterogeneous enzyme immunoassay. In 1-6 years after convalescence the levels of anti-PA and anti-LF antibodies (at 75% and 96% detection rates respectively) were higher than on weeks 1-4 from the onset of the disease. In persons having had anthrax antibodies belonged mainly to IgG, and the anti-LF antibody level was higher than the anti-PA antibody level. In persons immunized with STI vaccine the detection rate of antibodies somewhat increased in 2-7 months after immunization, reaching, on the average, 72%, the antibody levels after primary immunization and regular annual booster immunization being similar. In 1-2 years after primary (booster) immunization the isolation rate of antibodies decreases to 21%. Specific features of postinfectious and postvaccinal immunity to anthrax and problems of retrospective diagnosis of this disease are discussed.     

Reactogenicity and immunologic activity of live enteric Sonne dysentery vaccine from a spontaneous mutant]

Live dysentery Sonne vaccine from a spontaneous mutant proved to be practically areactogenic and specifically harmless in oral immunization of children aged from 7 to 13 years, in doses of from 3 to 25 milliard live microbial cells and in single and triple immunization schemes. Weak reactions of the gastro-intestinal tract were noted with the same frequency (1.7%) in children immunized with the vaccine and in children given placebo (2.2%). There proved to be a significant increase in the serum of the immunized persons of the level of specific hemagglutinins, and also of the IgA-and IgM-titers in 82% of the persons vaccinated; they persisted at a high level for 2 months. The appearance of IgA-antibodies in high titres in the persons vaccinated orally pointed to a marked local and general immunological activity of the live dysentery Sonne vaccine from the spontaneous mutant processing the capacity to survive in the intestine of children for a long time.     

Experience with vaccine prophylaxis of hepatitis B among different groups of children

The immunological activity of different vaccines against hepatitis B was evaluated in the Hepatological Center organized on the basis of the Infectious Hospital in Tula. Newborn infants were immunized with the use of the following vaccines: Engerix B (Belgium), Combiotech (Russia), Euvax B (Aventis Pastèur, South Korea). Altogether, after the full course of immunization anti-HBs were detected in 76 children out of 81 (in 93.8%). Vaccine Engerix B, when introduced according to the schedule 0-1-2-12 months, exhibited high immunogenic properties in a group of infants born of women with persistent HBs-antigenemia. Anti-HBs at a concentration exceeding 1000 I.U./I could be detected in 84.6%. In another group of children immunized according to the schedule 0-1-6 months first with vaccine Combiotech at the age of 0 and 1 month, then (at the age of 6 months) with vaccine Euvax, the presence of postvaccinal anti HBs at protective concentration was registered in all children. After immunization against hepatitis B with the use of all above-mentioned vaccines introduced according to both schedules high immunological activity and safety of immunization were noted.     

A calendar of prophylactic inoculations in wide practical use

The validity of immunizations, made in due time in children aged up to 7 years in accordance with the approved immunization schedule, is analyzed in this work. The content of antibodies to diphtheria, tetanus and poliomyelitis antigens in children immunized in accordance with the old and new schedules has been studied. This study has revealed that the injection of adsorbed DPT vaccine to children aged 3-4 months induces fully valid immune response to all antigens under study. The level of measles and parotitis antibodies after the injections of measles and parotitis vaccines, introduced separately and simultaneously, has been measured. The simultaneous administration of these preparations did not decrease the levels of immunity to parotitis and measles.     

Whooping cough morbidity and inoculation status

The analysis of pertussis morbidity and the state of immunity to pertussis has made it possible to evaluate the existing epidemiological situation as unfavorable. The restraining influence of specific prophylaxis on the epidemic process of pertussis becomes weaker due to the growing number of nonimmunized children; for this reason, the maximum morbidity rate in pertussis is observed among children under 5 years of age, as it was at the period before the introduction of mass immunization against pertussis. To prevent further possible increase in the intensity of the epidemic process of pertussis and in the severity of the clinical course of the disease, the number of children under 3 years of age, not immunized against pertussis, must be reduced by limiting the number of children exempted from immunization on medical grounds and by increasing the proportion of children immunized from the age of 3 months.     

Immunization using an Apo B-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E (-/-) mice

Immune system modulates atherosclerosis and immunization using homologous LDL reduces atherosclerosis in hyperlipidemic animals. The nature of athero-protective antigenic epitopes in LDL remains unclear. We have recently identified nearly a 100 antigenic epitopes in human apo B-100 and in this study we evaluated the effects of immunization with two such epitopes on atherosclerosis in hypercholesterolemic apo E (-/-) mice. Male apo E (-/-) mice were immunized at 6-7 weeks of age with two different apo B-100 related peptide sequences using alum as adjuvant and mice immunized with alum alone served as controls. Peptide-2 immunization reduced aortic atherosclerosis by 40% and plaque inflammation by 80% compared to controls without a reduction in circulating cholesterol levels whereas Peptide-1 immunization had no effect. Peptide-2 immunization also reduced the progression of aortic lesions when mice were immunized at 16 weeks of age, suggesting the possibility of immuno-modulation in treating established atherosclerosis. The athero-protective effect of Peptide-2 immunization was absent in splenectomized mice but could be conveyed to non-immunized mice via adoptive transfer of splenocytes from peptide-2 immunized mice. In conclusion, immunization with a specific apo B-100 related peptide sequence reduces aortic atherosclerosis and plaque inflammation. Such acquired immunity and athero-protective effect appears to be mediated by splenocytes. These data demonstrate the feasibility of peptide based immunomodulating therapy for atherosclerosis.     

Total immunization of children against influenza decreases morbidity in a number of diseases among elderly persons during influenza epidemic

Immunization of children aged 3-6 years in kindergartens and school children aged 7-17 years against influenza with inactivated influenza vaccine was carried out in two districts of the Moscow region. The comparison of morbidity in influenza-like diseases among the immunized children with that among nonimmunized children in control districts revealed that the effectiveness of immunization was 60.9% in kindergartens and 68.8% in schools. The analysis of morbidity in a number of diseases among 158,451 elderly persons not immunized against influenza demonstrated that, in comparison with the control districts, in those districts where mass immunization of children was carried out morbidity in influenza-like diseases among elderly persons was 3.4 times lower and, out of other 10 diseases under study, morbidity in 8 diseases was 1.5-2.6 times lower. As indicated by the data obtained in this study, total anti-influenza immunization of children in organized groups not only essentially decreased influenza morbidity among children, but also greatly decreased morbidity in influenza and a number of diseases, appearing as complications of influenza infection, among nonimmunized elderly persons during influenza epidemic.     

Oral and intranasal administration of somatostatin DNA vaccine mediated by attenuated Salmonella enterica serovar Typhimurium to promote growth of piglets

An attenuated strain of Salmonella typhimurium has been used as a carrier for oral and intranasal genetic immunization. Here, we evaluate the efficacy of a vaccine strain of S. typhimurium. CSO22 (pGM-CSF/SS, plasmid granulocyte-macrophage colony-stimulating factor/somatostatin) expressing two copies of SS genes. A total of 115 piglets, aged 2 months old, were either orally or intranasally immunized against the vaccine strain CSO22 (pGM-CSF/SS) with three dosages (5 × 10(10) colony forming units (CFU), 5 × 10(9) CFU and 5 × 10(8) CFU). For oral immunization, the specific anti-SS antibodies were detected in the immunized piglets. The levels of SS antibodies in the high-dose immunized group (5 × 10(10) CFU) were significantly higher than that in the phosphate buffered saline immunized group (P < 0.01) and 40% of animals were positive in SS antibodies in the high-dose immunized group. Moreover, the weight gain of the high-dose group was increased by 20.86%, 10.26% and 15.30% during 4, 8 and 12 weeks, respectively, after immunization in comparison to the control. For intranasal immunization, the growth of the low-dose group was increased by 10.23% in the whole test period (12 weeks). In conclusion, our results suggest that the recombinant strain could elicit anti-SS antibodies and improve the growth performance of immunized piglets, and that the oral immunization program is better than the intranasal program.     

Effect of the heterogeneity of persons vaccinated, with respect to the state of their immune system, on the intensity of the immune response

Prior to the immunization of children aged 3-7 years with parotitis vaccine the state of their immune system was evaluated by the determination of the concentration of IgM, IgG and IgA, the ratio and absolute numbers of T- and B-lymphocytes, the intensity of the blast transformation of lymphocytes. This study revealed that the group of immunized children was essentially heterogeneous with respect to the state of their immune system: in 79.9% of the children all immunological characteristics were normal, in 20.1% of the children some deviations from the characteristics considered to be normal for their age (gammopathy, eosinophilia, the deficiency of T- and B-lymphocytes, a decrease in the intensity of their blast transformation, the leftward shift of the leukocytic formula) were noted. The intensity of humoral immune response in children with deviations from normal characteristics peculiar to their age was significantly lower than in children with normal immunological characteristics. On the basis of these results, the immunological rehabilitation of the risk group among the children to be immunized is recommended.     

GnRH or eCG treatment fails to restore reproductive function in GnRH immunized ewes

This study was designed to evaluate the potential of using eCG or GnRH in restoring reproductive functions in GnRH immunized ewes. Thirty-three multiparous Kivircik ewes were randomly assigned into either control group (n=11) or immunization group (n=22). Ewes were immunized against GnRH by injecting with a cocktail of ovalbumin-LHRH-7 (ovalbumin-GnRH-7) and thioredoxin-LHRH-7 (thioredoxin-GnRH-7) fusion proteins generated by recombinant DNA technology in April. 500 IU eCG or 0.008 mg GnRH analogue was used to induce ovulations. Serum GnRH antibodies were present in animals of the immunized group beginning the second week after the first immunization and maintained throughout the study (14 months). Immunization caused anestrus in immunized ewes. eCG or GnRH analogue administration given after 14 days progestagen (20 mg fluorogestone acetate, FGA) treatment during breeding season (mid July) did not induce ovulation in these ewes. Two more attempts with single or multiple eCG injections failed to induce ovulation in this group as well. It appears that the gonadotropin stimulation was not of adequate time since neither eCG nor GnRH administration was able to restore reproductive function in immunized animals. The immunization effect lasted more than a year. These results suggest that GnRH immunization exerts its effect via the hypothalamo-pituitary axis and that more than such stimulation is required to overcome the reproductive suppression.     

Sustained testicular atrophy in bulls actively immunized against GnRH: potential to control carcase characteristics

The objectives were to determine whether active immunization against gonadotrophin releasing hormone (GnRH) induced a long-term suppression of testicular function in bulls, and to ascertain the effects of immunization against GnRH on carcase and meat quality characteristics. In experiment 1, 6-month-old Zebu bulls were assigned to: control (n=25), no treatment; immunized (n=31), immunized against GnRH at 0 and 4 months (anti-GnRH(2)), with a sub-set of bulls (n=17) immunized again at 10 months (anti-GnRH(3)). After the second immunization, testicular growth ceased for 2 months in 14/31 (45%) bulls and for at least 6 months in 17/31 (55%) bulls. Among the latter bulls (anti-GnRH(3)) the testes did not grow for >1 year after the third immunization in 5/17 (30%) bulls. In experiment 2, 22-month-old Zebu bulls were assigned to: control (n=14), no treatment; immunized (n=17), immunized against GnRH at 0, 2 and 4 weeks. The testes decreased (P<0.05) in size for 2 months after immunization in 11/17 (65%) bulls and then re-initiated growth, whilst in 6/17 (35%) bulls the testes continued to decrease in size for 4 months and did not re-initiate growth for 1 year. At slaughter, the latter immunocastrated bulls had carcase and meat quality characteristics the same as contemporary bulls that had been castrated before puberty. The findings demonstrated that active immunization against GnRH can induce a long-term suppression of testicular function in a proportion of bulls. Also, when bulls are immunocastrated after puberty, carcase and meat quality traits change from those typical of entire bulls to traits that are characteristic of long-term castrated bulls.     

The effects of immunization of sheep with Trichostrongylus colubriformis larvae on worm burdens acquired during grazing

The effects of immunization of sheep with Trichostrongylus colubriformis larvae on worm burdens acquired during grazing. International Journal for Parasitology 19: 177-181. Romney sheep, reared helminth-free in pens to 5 months of age, were immunized against Trichostrongylus colubriformis by giving two doses of 200,000 T. colubriformis infective larvae at 15 day intervals to assess protection from natural challenge during grazing. Five immunized sheep and five unimmunized sheep were grazed on infested pasture for 4 weeks, and were then returned to the pens for 4 weeks before slaughter. Worm burdens, gastrointestinal histology and mucus antiparasite activity were examined at slaughter. Faecal egg counts and haematological examinations were carried out at regular intervals throughout the trial. Significant protection (P less than 0.05) was afforded immunized sheep against adult T. colubriformis (87%), T. axei (67%), Nematodirus spathiger (91%) and Ostertagia spp. (42%). Greater numbers of immature Nematodirus spp. and Ostertagia spp. were present in immunized sheep Overall, a significant (P less than 0.05) 42% reduction in total nematode burdens was afforded by immunization of the sheep with T. colubriformis larvae. Immunized sheep had significantly (P less than 0.05) more globule leukocytes, mast cells and eosinophils in gastrointestinal tissue and significantly (P less than 0.05) higher levels of mucous antiparasite activity than unimmunized sheep. Haematological observations showed some sheep had transient eosinophilia during immunization or grazing. Both immunized and unimmunized sheep showed depressed (P less than 0.05) total leukocyte counts during grazing which returned to pre-grazing levels within 1 week of return of the sheep to the pens. Overall, haematological parameters reflected parasite challenge and were unrelated to worm burdens acquired.     

Epidemiological and immunological criteria of the effectiveness of immunization with adsorbed DPT vaccine by the old and new schedules

The study revealed that the immunization of children with adsorbed DPT vaccine from the age of 3-4 months, as compared with the immunization of children from the age of 5-6 months, did not lead to an essential increase in the coverage of children with immunization at the period under study (1970-1983) and did not affect the total level of pertussis morbidity, as well as the proportion of children aged up to 1 year in the total number of pertussis cases. Children immunized at an early age produced antibodies in titers, equivalent to the titers in older children, but their immunity against pertussis, in contrast to their immunity against diphtheria and tetanus, was retained for a shorter period. The injection of adsorbed DPT vaccine at the age of 3-4 months was accompanied by a poorly pronounced increase in the content of IgG, the predominant synthesis of IgM and the suppression of the synthesis of IgA. The shift of the start of vaccination to the age of 3-4 months has probably some immunological grounds for diphtheria and tetanus, but it is premature with respect to pertussis.     

Protection of mice from rabies by intranasal immunization with inactivated rabies virus.

The mucosal immunization method is a needle-free alternative way of vaccination. This study evaluated the efficacy of mucosal immunization for rabies. Mice were intranasally administered five times with inactivated and concentrated rabies virus antigen (CRV) supplemented with or without cholera toxin (CT). The anti-rabies virus antibody titer of mice intranasally immunized with CRV plus CT (CRV/CT) was comparable to that of mice intraperitoneally immunized twice with the same amount of CRV. Virus neutralizing (VNA) titers of mice immunized intranasally with CRV/CT were slightly lower than those of intraperitoneally immunized mice. Both anti-rabies virus ELISA antibody and VNA titers of mice immunized with CRV without CT were significantly lower than those of mice immunized with CRV/CT. In mice intranasally immunized with CRV/CT, and intraperitoneally immunized mice, high levels of IgG(2a) antibody were detected, suggesting the activation of Th1-driven cellular immunity by the two ways of immunization. All immunized mice were challenged intracerebrally with a lethal dose of virulent rabies virus CVS strain. The survival rates of mice immunized with CRV/CT and CRV without CT were 67% and 17%, respectively, while the rate of intraperitoneally immunized mice was 100%. Antigen-specific whole IgG and IgG(2a), and VNA titers of survived mice were significantly higher than those of dead mice at the challenge day. These data suggest the possibility of intranasal immunization with inactivated antigen as a rabies vaccination strategy and the importance of a mucosal adjuvant such as CT.     

Clinical and immunological effect of vaccination against Haemophilus influenzae, type B, in children with disorders of the nervous system

Observations on 277 children aged 3 months to 4 years with lesions of the nervous system, immunized with vaccine Act-HIB (Aventis Pasteur, France), were carried out in groups of children. The significant decrease of the level of Hib nasopharyngeal carrier state in 3.3 times and the decrease of total morbidity in acute infections of respiratory and ENT organs in 2.7 times occurred after immunization was revealed. The immunological effect of immunization on the level of protective titers against H. influenzae, type b, in children with organic CNS lesions in children was shown.     

Immunization with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and effect of revaccination.

Previously we showed that mice immunized with a vaccinia virus vector expressing the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) gene (vaccinia/gD) were protected against both lethal and latent infections with HSV-1 for at least 6 weeks after immunization (K. J. Cremer, M. Mackett, C. Wohlenberg, A. L. Notkins, and B. Moss, Science 228:737-740, 1985). In the experiments described here, we examined long-term immunity to HSV following vaccinia/gD vaccination, the effect of revaccination with vaccinia/gD, and the impact of previous immunity to vaccinia virus on immunization with the gD recombinant. Mice immunized with vaccinia/gD showed 100, 100, and 80% protection against lethal infection with HSV-1 at 18, 44, and 60 weeks postimmunization, respectively. Protection against latent trigeminal ganglionic infection was 70, 50, and 31% at 6, 41, and 60 weeks postvaccination, respectively. To study the effect of reimmunization on antibody levels, mice vaccinated with vaccinia/gD were given a second immunization (booster dose) 3 months after the first. These mice developed a 10-fold increase in neutralizing-antibody titer (221 to 2,934) and demonstrated a significant increase in protection against lethal HSV-1 challenge compared with animals that received only one dose of vaccinia/gD. To determine whether preexisting immunity to vaccinia virus inhibited the response to vaccination with vaccinia/gD virus, mice were immunized with a recombinant vaccinia virus vector expressing antigens from either influenza A or hepatitis B virus and were then immunized (2 to 3 months later) with vaccinia/gD. These mice showed reduced titers of neutralizing antibody to HSV-1 and decreased protection against both lethal and latent infections with HSV-1 compared with animals vaccinated only with vaccinia/gD. We conclude that vaccination with vaccinia/gD produces immunity against HSV-1 that lasts over 1 year and that this immunity can be increased by a booster but that prior immunization with a vaccinia recombinant virus expressing a non-HSV gene reduces the levels of neutralizing antibody and protective immunity against HSV-1 challenge.     

Effect of vaccination against pneumococcal infection and influenza in children with asthma

Assessment of clinical course of asthma and IgG response in children with asthma immunized with pneumococcal polysaccharide vaccine (Pneumo 23) and influenza vaccine (Vaxigrip). 78 children aged 4 - 17 years old were allocated to two groups. Children from the 1st group were immunized against pneumococcal infection and influenza; children from 2nd group were immunized against pneumococcal infection only. Rate of asthma exacerbations in the 1st group of children decreased by 1.7 times compared with the period before vaccination, whereas the same rate in the 2nd group of children decreased by 1.5 times. It was accompanied by the increase of IgG level to antigens of pneumococcalvaccine in blood, which was observed in both groups. Vaccination did not result in increase of IgE levels. Immunization of children with asthma against pneumococcal infection with polysaccharide vaccine or combined immunization against pneumococcal infection and influenza reduced rate of asthma exacerbations and led to formation of immunity to vaccine strains of Streptococcus pneumoniae. Vaccination did not lead to sensitization of children.