Strain-specific antibodies as an indicator of the circulation of wild poliomyelitis viruses and their role in the formation of collective immunity in the population

Essential differences in the intensity of collective immunity to poliomyelitis in the donors of Moscow and Kaluga were established. To find out the nature of high characteristics of collective immunity to poliovirus, types 1 and 2, in the donors of Kaluga, strain-specific antibodies to wild and vaccine polioviruses were studied. In a considerable number of donors strain-specific antibodies to poliovirus, types 1 and 2, were detected. This made it possible to presume a sufficiently wide circulation of these viruses among the population of the city in the middle of the 20th century and, as a consequence, high level of collective immunity appeared. Strain-specific antibodies to poliovirus of type 3 were rarely detected. This made it possible to suggest that the circulation of viruses of this type among the population was limited. Immunity to viruses of this type was due only to immunization. For this reason the characteristics of collective immunity in the donors of Moscow and Kaluga coincided. The detection of strain-specific antibodies to poliomyelitis virus allowed to retrospectively form the opinion of the spread and time of the circulation of wild poliomyelitis viruses in the population.     

State of collective immunity to poliomyelitis in Moscow donors

Immunity induced by immunization with oral poliomyelitis vaccine has long been considered to last for life, similarly to immunity developing after infection with wild poliomyelitis virus. Vaccine virus cannot circulate among the immune population for a long time. The vaccination of children against poliomyelitis, carried out in the course of many years, has made it possible to suggest that a considerable number of immune persons were present among the adult population. The examination of 1,030 Moscow donors has revealed that antibodies to poliomyelitis virus of types 1, 2 and 3 were detected in 47.3%, 45.5% and 76.4% of the examinees respectively, the values of the average geometric titers being low. It is known that passages of poliomyelitis vaccine virus through nonimmune persons may result in emergence of revertant viruses with increased neurovirulence. The nonimmune adult population, especially the mothers of vaccinated and revaccinated children, may serve as favorable environment for the circulation of vaccine viruses and the appearance of revertant viruses.     

Assessment of the separate elements of an epidemiological overview of poliomyelitis today

The materials on the epidemiological supervision of poliomyelitis in a large city, carried out in 1972-1981, are presented. Two periods differing in morbidity rate, in the level of population immunity to poliomyelitis and in the activity of the poliovirus circulation are defined. The supervision of poliomyelitis is shown to be capable of influencing the course of the epidemic process of this infection provided that the individual elements of such supervision are correctly evaluated in different epidemic situations.     

Expanded program on immunization and its implementation in the Czech Socialist Republic

National immunization programs carried out in the CSR are here confronted with the EPI regional targets for Europe, a component of the WHO global program "Health for all by the year 2000". The EPI target diseases to be brought under control in Europe by 1990 include measles, poliomyelitis, diphtheria and neonatal tetanus; control of congenital rubella infection is to be achieved by the year 2000. The presented data show that Czechoslovakia has succeeded in implementing this program much ahead of the WHO time schedule. The elimination of measles infection was achieved in 1982, poliomyelitis was brought under control in 1961, and the effective diphtheria control has been in effect since the mid-1960s. Cases of neonatal tetanus are absent in the CSR since 1965, the annual incidence of postnatal tetanus is permanently 0.1-0.2 per 100,000 population. The goal of achieving the rubella-free status and thus the elimination of congenital rubella cases at country level is expected to be reached in the early 1990s. Implementation of the remaining WHO recommendations pertinent to infections other than EPI target diseases appears also satisfactory. Regular immunization against whooping cough, one of the oldest immunization programs in Czechoslovakia, succeeded in effectively eliminating this infection in the early 1970s. Selective immunization campaigns against influenza infection, introduced many years ago, help protect, together with a large-scale use of available chemoprophylactics, some 200,000 individuals every year in CSR. The hepatitis B immunization program was started in 1983 and is primarily limited to health service staff, which is in line with the existing WHO recommendations. Inception of the regular immunization program against mumps is planned for the beginning of 1987.     

The level of postvaccinal immunity to diphtheria, tetanus and poliomyelitis in relation to the number of inoculations]

The work was aimed at the comparative study of the intensity of immunity to diphtheria, tetanus and poliomyelitis, depending on the number of injections of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine and poliomyelitis vaccine, for the purpose of finding out the possibility of reducing the antigenic load given to children without diminishing the intensity of immunity. To determine the level of immunity to diphtheria and tetanus, 1900 children under school age were serologically studied by the micromethod in the passive hemagglutination test. The intensity of immunity to poliomyelitis virus was studied in 333 children by means of the neutralization test. The immunogenic properties of the diphtheria component of adsorbed DPT vaccine were found to be less pronounced than those of the tetanus component of the vaccine, which made it impossible to reduce the antigenic load by decreasing the number of vaccinations against diphtheria. The results of the study of postvaccinal immunity to poliomyelitis suggest that during the first and second year of life the course of vaccination against poliomyelitis may be reduced to 3 injections.     

Vaccination against polio should not be stopped

The striking 50-year-long decline in the incidence of poliomyelitis has stalled in the past 7 years, which has led to calls for an urgent re-assessment of eradication and post-eradication campaign strategies. The current plan of eliminating the circulation of wild poliovirus so that further immunization will be unnecessary does not take into account recent scientific data and political realities that limit the likelihood that this strategy can sustain prevention of the disease. It is crucially important that high levels of population immunity are maintained against polio in the foreseeable future.     

Humoral and cellular immunity factors in peroral vaccination with an S. typhimurium antigenic complex]

The role of individual immunity factors in protection from S. typhimurium infection was studied on mice immunized orally in a single administration with an antigenic complex obtained by the treatment of bacterial cells with hydroxylamine. The oral administration of this preparation induced the systemic and local transformation of the organism, which was manifested by the accumulation of antibody-producing cells in the immunocompetent organs (spleen, mesenteric lymph nodes) and the increase of the phagocytic activity of macrophages in peritoneal fluid. Cellular immunity factors were found to be important for the development of resistance to salmonellosis caused by S. typhimurium after oral immunization with the antigenic complex.     

Experimental study of vaccines against Salmonella typhimurium infection.

Serological and protective activities of vaccines from S. typhimurium and S. minnesota were studied. It has been demonstrated that active protection against infection in experimental salmonellosis in mice can only be obtained by immunization of the animals using vaccines from complete antigenic complexes isolated from S-strains. It has been found that expressed anti-infection immunity (unlike anti-endotoxic immunity) is induced to the same extent by either high-molecular components (2,000,000 daltons and more), showing great serological activity, or components with relatively low molecular weight (15,000--20,000 daltons) and minimum serological activity. Vaccines from Ra- and Re-strains of S. minnesota do not induce resistance to S. typhimurium infection in mice in either active protection tests or passive protection tests.     

Immunogenic dialyzable factor derived from a ribosomal fraction of Salmonella typhimurium III. Analysis of resistance induced by dialyzable factors

Dialyzable factors (DF) were prepared from ribosomal fractions of several organisms including rough mutants of Salmonella typhimurium LT2, salmonella species of different serogroups, other enteric bacteria and gram-positive organisms, and tested for their immunogenicity against S. typhimurium infection in mice. All of them conferred local resistance on mice challenged intramuscularly with S. typhimurium LT2 in the early stage of immunization before the establishment of delayed-type hypersensitivity (DTH) to salmonella antigens. Although DFs of enteric bacteria including rough mutants of S. typhimurium induced DTH to salmonella antigens, only DF of a two-heptose mutant of S. typhimurium LT2 afforded significant mouse protection but others only prolonged the mean time to death. DF of Listeria monocytogenes induced the cross-reacting immunity which afforded the low level of mouse protection as well as an increase in mean time to death without inducing DTH. Passive transfer of anti-O antibody did not enhance the mouse protection provided by each DF. Resistance conferred by DF of S. typhimurium LT2 consisted of two phases: (i) nonspecific macrophage activation resulting in reduction of organisms at the infected site, which became active in the early stage of immunization and (ii) salmonella-specific immunity capable of preventing systemic infection, which became active in the late stage of immunization.     

Separate transfer of mouse protection and delayed-type hypersensitivity with Salmonella typhimurium transfer factor

Delayed-type hypersensitivity (DTH) induced with Salmonella typhimurium transfer factor (TF) contributed to an increase in mean survival days of mice challenged with homologous organisms and afforded only a low level of host protection as determined by survival rate, compared with that obtained by active immunization. TF of other enteric bacteria could transfer DTH which is cross-reactive to salmonella antigen but did not afford host protection. Although TF of Listeria monocytogenes did not transfer the cross-reactive DTH, it could confer the significant increase in mean survival days against the lethal challenge with S. typhimurium. Listerial ribosomal vaccine conferred the high level of mouse protection without inducing DTH to salmonella antigen. The resistance generated upon active immunization with listerial ribosomal vaccine could be enhanced by the injection of S. typhimurium TF to the same level as that obtained after immunization with homologous ribosomal vaccine. Among salmonella TF, there could be no cross-reactive immunity between S. typhimurium and S. choleraesuis, although the cross-reactive DTH was observed. The DTH transfer ability of TF was sensitive to Pronase which could not affect the ability to transfer host immunity, but RNase could abolish the ability to transfer host immunity without impairing DTH transfer activity. These results suggest that in mouse typhoid infection, DTH is not associated with host protection as determined by survival rate.     

Enteroviruses in the XX and XXI centuries

The modern view of the role of enteroviruses in the eradication of poliomyelitis is presented. Enteroviruses were discovered in the XX century. In the 1950s they caused great epidemics of poliomyelitis and serous meningitis in many countries of the world. The introduction of oral poliomyelitis vaccine (OPV) into medical practice made it possible to eliminate the epidemics of poliomyelitis in a short time. Poliomyelitis morbidity was reduced to sporadic cases and in a number of regions disappeared. OPV produced non-specific influence also on the epidemics of serous meningitis, as well as on a case incidence. The eradication of poliomyelitis viruses and the cessation of immunization with OPV will not result in eradication of paralytic diseases. Paralytogenic viruses of 20 serotypes circulate in nature, and some of these viruses are capable of causing the outbreaks of severe paralytic diseases. The authors propose either to retain immunization with OVP as tour immunizations with monovaccine of type 2, or to create new live enterovirus vaccines on the basis of avirulent enterovirus strains.     

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.     

Congenital absence of the gallbladder; case report

The virus of human poliomyelitis has been demonstrated in excretions before onset of the disease, during the disease, and in convalescence. It may be confused with different viruses likely to be found in the same sources in clinical conditions resembling poliomyelitis.Immunologic differences between strains of poliomyelitis virus have been detected so that three types are now evident. The distribution of these types and their importance as causes of epidemics are not known. This multiplicity of immunologic types is an important factor in considering immunization of humans. Commercial manufacture of vaccines faces many technical problems. Recently the Coxsackie virus has been demonstrated in humans with a disease closely resembling poliomyelitis.     

Congenital Absence of the Gallbladder: Case Report

The virus of human poliomyelitis has been demonstrated in excretions before onset of the disease, during the disease, and in convalescence. It may be confused with different viruses likely to be found in the same sources in clinical conditions resembling poliomyelitis.Immunologic differences between strains of poliomyelitis virus have been detected so that three types are now evident. The distribution of these types and their importance as causes of epidemics are not known. This multiplicity of immunologic types is an important factor in considering immunization of humans. Commercial manufacture of vaccines faces many technical problems.Recently the Coxsackie virus has been demonstrated in humans with a disease closely resembling poliomyelitis.     

Mechanism of the protective immunity against murine typhoid: persistence of salmonella L forms in the liver after immunization with live-cell vaccines

Abstract Live-cell vaccines of Salmonella typhimurium , either a sub-lethal dose of a wild-type (strain LT2) or a high dose of its two-heptose Rd₁ mutant (strain SL1004), induced acquired resistance to murine typhoid, which remained 180 days after immunozation. Growth of S. typhimurium as a bacillary form ceased between days 30 and 60 of immunization, but L forms of this bacterium colonized the liver (the mean number of L forms in the liver: 600 L-forming units) even at 180 days post-immunization. In contrast, a high inoculum of either a Ra mutant (strain TV148) of strain LT2 or S. schottmülleri 8006 sharing the same O antigenic components with those of S. typhimurium induced only a short-lived protection in proportion to the number of L forms in the liver, and the protective immunity was lost before day 180. However, there was no significant difference in the salmonella-specific T-cell responses among groups of immunized mice on day 180 of immunization. A lethal infection with strain LT2 in mice which had been immunized 75 days previously with living cells of strain SL1004 resulted in a rapid clearance of the challenge inoculum, together with a rapid elevation of anti- S. typhimurium antibody responses. Thus, the present data suggest that the long-lived immunity conferred upon live S. typhimurium vaccines is attributable to the colonization of this bacterium in the liver as L forms and the ability to colonize the liver as L forms is independent of the brain length of salmonella O-antigens.     

Protective immunity induced by systemic and mucosal delivery of DNA vaccine expressing glycoprotein B of pseudorabies virus

A murine model immunized by systemic and mucosal delivery of plasmid DNA vaccine expressing glycoprotein B (pCIgB) of pseudorabies virus (PrV) was used to evaluate both the nature of the induced immunity and protection against a virulent virus. With regard to systemic delivery, the intramuscular (i.m.) immunization with pCIgB induced strong PrV-specific IgG responses in serum but was inefficient in generating a mucosal IgA response. Mucosal delivery through intranasal (i.n.) immunization of pCIgB induced both systemic and mucosal immunity at the distal mucosal site. However, the levels of systemic immunity induced by i.n. immunization were less than those induced by i.m. immunization. Moreover, i.n. genetic transfer of pCIgB appeared to induce Th2-biased immunity compared with systemic delivery, as judged by the ratio of PrV-specific IgG isotypes and Th1- and Th2-type cytokines produced by stimulated T cells. Moreover, the immunity induced by i.n. immunization did not provide effective protection against i.n. challenge of a virulent PrV strain, whereas i.m. immunization produced resistance to viral infection. Therefore, although i.n. immunization was a useful route for inducing mucosal immunity at the virus entry site, i.n. immunization did not provide effective protection against the lethal infection of PrV.     

Immunity to Plasmodium yoelii: kinetics of the generation of T and B lymphocytes that passively transfer protective immunity against virulent challenge

Adoptive immunization of A/Tru mice with splenic B cells or T cells from syngeneic donors with a primary, nonvirulent, Plasmodium yoelii (17X) infection confers on these recipients the capacity to resist a challenge infection with a virulent strain (YM) of P. yoelii. Unfractionated spleen cells as well as spleen cells enriched for T or B cells capable of transferring protective immunity were detected as early as Day 7 of the primary nonvirulent infection, and reached peak levels on Day 14. Spleen cells that were harvested from donor animals after resolution of the immunizing infection [on Days 21 or 28] were incapable of transferring protective immunity. The capacity of 7-day immune spleen cells to transfer immunity could be abolished by pretreatment with mitomycin C. In addition, it was found that immunocompetent recipient mice were required for successful adoptive immunization, since thymectomized, irradiated, bone marrow reconstituted mice infused with immune spleen cells failed to survive lethal challenge infections.     

GM-CSF transgene-based adjuvant allows the establishment of protective mucosal immunity following vaccination with inactivated Chlamydia trachomatis

Cellular and humoral immune responses induced following murine Chlamydia trachomatis infection confer almost sterile protection against homologous reinfection. On the other hand, immunization with inactivated organism induces little protective immunity in this model system. The underlying mechanism(s) that determines such divergent outcome remains unclear, but elucidating the mechanism will probably be important for chlamydial vaccine development. One of the distinct differences between the two forms of immunization is that chlamydia replication in epithelial cells causes the secretion of a variety of proinflammatory cytokines and chemokines, such as GM-CSF, that may mobilize and mature dendritic cells and thereby enhance the induction of protective immunity. Using a murine model of C. trachomatis mouse pneumonitis lung infection and intrapulmonary adenoviral GM-CSF transfection, we demonstrate that the expression of GM-CSF in the airway compartment significantly enhanced systemic Th1 cellular and local IgA immune responses following immunization with inactivated organisms. Importantly, immunized mice had significantly reduced growth of chlamydia and exhibited less severe pulmonary inflammation following challenge infection. The site of GM-CSF transfection proved important, since mice immunized with inactivated organisms after GM-CSF gene transfer by the i.p. route exhibited little protection against pulmonary challenge, although i.p. immunization generated significant levels of systemic Th1 immune responses. The obvious difference between i.p. and intrapulmonary immunization was the absence of lung IgA responses following i.p. vaccination. In aggregate, the findings demonstrate that the local cytokine environment is critical to the induction of protective immunity following chlamydial vaccination and that GM-CSF may be a useful adjuvant for a chlamydial vaccine.     

Antidiphtheria immunity in adult population of the Orenburg region

The analysis of the level of antidiphtheria immunity in different age group of the adult population has shown that postvaccinal immunity resulting from immunization with adsorbed DT toxoid with reduced antigen content gradually decreases after the period of two years. The immune stratum remains sufficiently numerous only among persons aged 18-27 years (93.3%), persons over 38 years constitute a high risk group with respect to the possibility of diphtheria infection: the proportion of persons protected against this infection amounts to 71.3% in the age group of 38-47 years and 54.9% in the age group over 48 years, that is not sufficient.     

Immunoprophylaxis of poliomyelitis in Ukraine with the use of inactivated vaccine

In connection with the cessation of the circulation of "wild" poliovirus on the territory of the European region, including Ukraine, the strategy of the vaccinal prophylaxis of poliomyelitis is reviewed. Its main aims are the creation of a high level of the specific protection of the population, the prophylaxis of vaccine-associated paralytic poliomyelitis and a decrease in the intensity of the circulation vaccine polioviruses. These aims may be achieved only by the inclusion of vaccinations with inactivated poliomyelitis vaccine (IPV) into the immunization schedule. IPV "Imovax Polio" produced by the firm "Aventis Pasteur" (France) has been shown to have low reactogenicity and high effectiveness, especially with respect to type 3 poliovirus, under the conditions of Ukraine. On the basis of our studies all children, starting from the age of 3 months, are recommended to be vaccinated first with two injections of IPV, followed by further immunization with oral vaccine.