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[Results of simplified immunization schedules in the developing countries].

The results of studies on the immunization of people in developing countries with vaccines adsorbed on calcium phosphate are presented in this paper. Several programs which were studied with various organizations cooperating and which were intended to simplify vaccination campaigns brought us to the following conclusions: --that immunization against diphtheria and tetanus by two injections with an interval of one year between them is effective, --that two injections of inactivated trivalent poliomyelitis vaccine followed up by booster one year later ensure that 90% of the infants are protected, --that it is possible to vaccinate pregnant women by one or two injections of tetanus vaccine and protect both mothers and newborn babies against tetanus, and --that combined vaccines which enable simultaneous immunization of subjects against a maximum of infections are possible.

Developing Countries

Immunization schedules for the new human diploid cell vaccine against rabies.

Clinical and antibody responses of human volunteers to four different serial production lots of human diploid cell vaccine (HDCV) each with a different antigenic value are described. Three to four doses of HDCV administered over a period of 14 days produced high levels of virus neutralizing antibodies with an average titer up to 20 times higher than the titer elicited by four doses of duck embryo vaccine. Antibodies were still present one year after completion of vaccination. Only minimal differences in antibody response could be observed between groups receiving vaccines of different antigenic values. Untoward reactions to the vaccine were few. The possibility of using the vaccine as part of postexposure human prophylaxis against rabies is discussed.

Animals

[Utilization of the MVA-immunization schedule from the view point of the public health service].

The world-wide smallpox eradication program sponsored by the WHO has been successful. Furthermore the legislation regarding smallpox vaccination in the Federal Republic of Germany has been given a new form. The place of the previous mass-vaccination has been taken by vaccination of individuals. Under this aspect safe procedures for vaccination are required. Any vaccination used by Public Health Service has to fulfill the following criteria: High protection against the disease without adverse side-effects or risks; it should be simple to administer and applicable under ordinary circumstances. For primary vaccination against smallpox the MVA-vaccination meets these demands entirely. It is reported about own experiences with 700 vaccinations using the attenuated virus "MVA"; complete documentation is given. Not a single complication nor any adverse side-effects have been seen. The Public Health Service has gained great experience in the field of vaccination. It is responsible for the protection of the individual as well as the public, as it is undesirable that there develops and unvaccinated group within the population. The individual claim a complete protection through vaccination which should be absolutely free of any risk.

Adolescent

A two-dose schedule for immunization of infants using a more concentrated DPT-vaccine.

In a controlled field-trial in infants in the Philippines, a two-dose schedule with an interval of 6 months between injections using a concentrated adsorbed DPT-vaccine was evaluated. The serologic response against the three components in the vaccine was satisfactory, whereas the side-effects in the concentrated vaccine group did not differ from those observed in a control DPT group. After two injections, the coverage percentage with DPT-vaccine was shown to be higher than 70%. Two implications of the introduction of the two-dose DPT-immunization schedule are discussed, i.e. (a) the possibility of using it as the nucleus of a complete schedule including immunization against poliomyelitis, BCG, smallpox and measles, and (b) the consequences which the interval of 6 months might have on the epidemiological spread of B. pertussis infections.

Age Factors

Effect of vaccination schedule on immune response of Macaca mulatta to cell culture-grown Rocky Mountain spotted fever vaccine.

The effect of vaccination schedule on the immune response of Macaca mulatta to formalin-inactivated chicken embryo cell culture (CEC)-grown Rickettsia rickettsii vaccine was studied. Schedules consisted of inoculation on day 1 only, on days 1 and 15, on days 1 and 30, on days 1, 8, and 15, or on days 1, 15, and 45. Humoral antibody measured by microagglutination and indirect immunofluorescence and resistance to challenge with 10(4) plaque-forming units of yolk sac-grown R. rickettsii were assessed. Seroconversion was noted in all monkeys after the first dose of vaccine. A second dose administered 8 or 15 days after the primary infection, or a third given 7 or 30 days after the second, produced no long-term effect on antibody titer. Only monkeys given two doses of vaccine at a 30-day interval showed an increase in antibody titer during the period before challenge. Vaccination with one, two, or three doses of CEC vaccine prevented development of rash and rickettsemia after challenge. The two-dose schedules appeared to induce the highest degree of resistance to challenge, as indicated by unaltered hematological parameters and body temperature in monkeys. The one- and three-dose schedules were somewhat less effective, in that some challenged monkeys within each group displayed febrile and leukocyte responses associated with Rocky Mountain spotted fever infection. Our data suggest that administration of two doses of CEC vaccine at 15- or 30-day intervals is the immunization schedule of choice.

Agglutination Tests

Reduction of metastatic rate by immunotherapy: a comparison of the immunogenic properties of metastasizing tumor cells versus tumor cells in the primary mass.

The vasculature of a poorly immunogenic, highly metastatic transplantable fibrosarcoma (T-241) maintained in the femoral muscle of C57BL/6J mice was perfused. This permitted collection of tumor cells which had invaded into the tumor vascular channels (ie, metastasizing tumor cells). Also collected as a separate population were tumor cells from the primary tumor mass. Immunization was carried out with these cell populations in conjunction with BCG and the effect on the growth of primary tumor and metastatic rate was evaluated following rechallenge with unfractionated tumor cells. The rate of tumor growth at the primary site was not affected by any of the immunization schedules. However, immunization with venous effluent cells (metastasizing tumor cells) and BCG was two times more effective in reducing the number of pulmonary metastases than immunization using tumor cells isolated from the primary tumor mass. Passively transferred spleen cells from donors immunized with the cell populations listed above had exactly the same effect, that is, no effect on the growth of the primary tumor, but a dramatic reduction in the metastatic rate when effluent tumor cells were used to immunize cell donors. The data point to an antigenic heterogeneity with this particular transplantable tumor.

Animals

Protection against group B meningococcal disease. III. Immunogenicity of serotype 2 vaccines and specificity of protection in a guinea pig model.

Protein vaccines were prepared from the serotype antigen of group B Neisseria meningitidis strain M986. The detergents Triton X-100, Emulphogene BC-720, and deoxycholate were used to removed the toxic lipopolysaccharide (LPS) portion of the serotype antigen. The LPS was most preferentially solubilized by Emulphogene. Guinea pigs were immunized with one or two doses of vaccine given intramuscularly without adjuvants and the antibody response quantitated by an enzyme-linked immunosorbant assay. Immunization with graded doses of vaccine between 25 to 200 microgram protein indicated a wide range of effective dosage and that a two-dose immunization schedule was superior to a single immunization. The vaccines elicited peak mean serum antibody levels of approximately 30 microgram/ml with bactericidal titers of 1:1,600-1:6,400. The peak antibody levels occurred 5-6 wk after immunization and persisted above preimmune levels for several months. To evaluate the protective effects of immunization, stainless steel springs were implanted subcutaneously into the guinea pigs. The resulting chambers, in unimmunized animals, could be infected with less than 100 type 2 organisms. A single 25-50 microgram dose of vaccine protected 50% of animals from challenge by 5 X 10(5) type 2 meningococci, and as little as 1 microgram vaccine significantly reduced the severity of infection. A two-dose immunization schedule was best and provided nearly complete protection for at least 4 mo against type 2 strains of meningococcal groups B, C, and Y.

Animals

Immunization for the common communicable diseases.

Infectious diseases have dropped from the limelight in developed countries with the advent of immunization and antibiotics, but their worldwide significance in the terms of morbidity and mortality is still considerable. Whereas there are grounds for substantial differences in immunization schedules between the developed and developing countries, the acceptance of simplified immunization schedules in the former remains a crucial factor for gaining significant cover of young children and success in control of the target diseases. In the developed countries, continuing surveillance and re-evaluation of programmes is necessary to ensure that the benefits so far obtained are maintained. This paper summarizes the approach to immunization programmes both in developing countries and in Australia, and outlines the schedule recommended by the National Health and Medical Research Council at its 85th Session in June, 1978.

Adolescent

Vaccines and vaccinations in the under-fives in Ghana, a tropical developing country.

In this paper, an attempt has been made to focus attention on the important childhood killer but immunizable diseases in Ghana, giving where available morbidity and mortality figures. Immunization schedules currently adopted in Ghana are discussed in the light of immunological considerations, the half-life of acquired maternal antibodies and from the point of view of known epidemiological patterns of these immunizable diseases. An attempt was thus made to justify the adoption of the immunization schedules currently in force in Ghana. Problems relating to some of the vaccines used in immunization of the under-fives in Ghana have been discussed in the light of personal experiences and the experiences of other colleagues, giving--where possible--suggestions for improvement. Finally, the paper delineates problem areas in immunization programmes of the under-fives in Ghana.

Bacterial Vaccines

Effects of dose and schedule of immune stimulant on efficacy of combination Corynebacterium parvum-cyclophosphamide treatment for a murine mammary adenocarcinoma.

Certain variables which might influence the outcome of combining cytotoxic drug and immune stimulant therapy were studied to optimize the effectiveness of Corynebacterium parvum combined with cyclophosphamide (CY) as treatment for a murine mammary adenocarcinoma (CaD2). Optimal effects of combined C. parvum-CY treatment in the CaD2 system were obtained when 443 to 1400 microgram of this immune stimulant per mouse were injected 2 to 3 days after CY chemotherapy and when combination treatment was continued on a weekly basis. The most critical factors contributing to the effectiveness of combination treatment in this system were the dose of C. parvum and the treatment frequency. The interval between chemotherapy and immune stimulant therapy was less critical to the outcome of combination treatment. Combination treatment given once or weekly significantly decreased tumor size in comparison to single or weekly CY treatment. A single treatment with CY and C. parvum significantly improved the survival over mice given a single CY treatment, but weekly CY and C. parvum treatment did not increase the survival over mice, given weekly chemotherapy.

Adenocarcinoma