Feasible improvements in vaccines in the Expanded Programme on Immunization.

Feasible improvements in existing vaccines of the Expanded Programme on Immunization are reviewed. The toxicity of pertussis vaccines can probably be reduced and the immunogenicity increased by recently instituted improvements in purity and selectivity. Candidate vaccines containing inactivated pertussis toxin, with or without other components, are in use in Japan and in controlled trials elsewhere. Inactivated poliovirus vaccines have been improved over the past decade and presently show promise of inducing immunity with as few as two doses administered in infancy. At the same time, improved methods for delivering the oral poliovirus vaccine through mass vaccination campaigns are being increasingly employed throughout the developing world. Major improvements in the measles vaccine will probably come from the development of new stabilizers and the use of vaccines that are immunogenic in the presence of maternal antibody.

PIP: The toxicity of pertussis vaccines can probably be reduced and the immunogenicity increased by recent improvements in purity and selectivity. Inactivated poliovirus vaccines show promise of inducing immunity with 2 doses administered in infancy. The Expanded Program on Immunization (EPI) uses the diphtheria-tetanus-pertussis (DTP) vaccine, poliovirus vaccine, and measles virus vaccine. The incidence of serious toxicity (particularly screaming fits, attacks of pallor, or unusual behavior) and encephalitis is very low. A superior partially purified pertussis vaccine was developed by Sato that contained both the pertussis toxin and filamentous hemagglutinin. With the toxicity of purified-component vaccines reduced, the relevant pertussis antigens can be increased to the point where 2 doses will suffice. The present live oral polioviruses vaccine (OPV) and inactivated poliovirus vaccine (IPV) are prone to thermal instability and a cold chain may be a necessary component of immunization with live poliovirus vaccine in the near future. It was shown that 4th and 5th doses of OPV given at 4-week intervals after the 3rd dose elevated the proportion of infants who developed serum antibody to types 1, 2, and 3 antigen from 69%, 90%, and 76%, respectively, up to 83%, 96%, and 82%. DTP vaccine improved to 2 doses is adequate for initial coverage then full immunization for DPT, poliomyelitis, and measles at 3 and 9 months of age. Vero cells of a heteroploid karyotype and of an indefinite lifespan were used to develop a poliovirus vaccine, as they do not produce tumors in rodents. WHO and the US Food and Drug Administration accepted them as safe as cell substrates for certain purified viral vaccines. Measles virus vaccines also have thermal instability and immunogenicity. Thermal instability was greatly reduced with the introduction of buffered glycerol-sorbitol before lyophilization. Immunogenicity in the presence of maternally derived antibody while indicating successful immunization also indicates susceptibility to measles. In a trial of aerosolized vaccine in Mexican children of different ages using the Edmonston-Zagreb (E-Z) vaccine and the Edmonston-Swartz (E-S) vaccine, successful immunization was high even in 6-month-old infants with the E-Z strain but not with the E-S strain. Both OPV and IPV will continue in general use and improvements will come from more efficient delivery schemes, particularly pulse immunization.

Efficacy and safety of vaccination of marrow transplant recipients with a live attenuated measles, mumps, and rubella vaccine.

Long-term immunity to measles, mumps, and rubella viruses was studied in 57 patients after allogeneic bone marrow transplantation. Among patients who were seropositive at the time of transplant, 51% had retained antibodies to measles, 42% had retained antibodies to mumps, and 76% had retained antibodies to rubella 2 y later. There was no difference in the ability to retain antibodies to these viruses between patients with and those without chronic graft-versus-host disease (GVHD). Twenty seronegative patients without active chronic GVHD or ongoing immunosuppressive treatment were vaccinated with a live attenuated trivalent vaccine against measles, mumps, and rubella. No early or late side effects were detected after the vaccinations. The percentages of patients who seroconverted after vaccination were 77%, 64%, and 75% for measles, mumps, and rubella, respectively. Vaccination of transplant recipients with a live attenuated vaccine against measles, mumps, and rubella is safe and usually effective 2 y after transplant if the patients do not have active chronic GVHD or ongoing immunosuppressive treatment at the time of vaccination.

Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide.

A toxoid vaccine, composed of purified pertussis toxin inactivated with H2O2 (NICHD-Ptxd), was developed on the basis of evidence that serum neutralizing antibodies (antitoxin) would confer immunity to pertussis. In vivo and in vitro assays of NICHD-Ptxd showed only trace or nondetectable levels of pyrogenic, adenosine diphosphate-ribosyltransferase, binding and pharmacologic activities. Nevertheless, about 40% of the antigenicity of pertussis toxin was retained. Adult volunteers were injected, two times 6 weeks apart, with either 10 (n = 21), 50 (n = 25), or 75 (n = 30) micrograms/dose of one lot, Ptx-06, adsorbed onto AI(OH)3. Neither fever nor changes in the levels of leukocytes, lymphocytes, fasting blood glucose, or insulin were observed in the volunteers. The optimal immunizing dose, 50 micrograms, induced levels of antitoxin (geometric mean (GM) 302 U) comparable to those found in eight adults convalescent from pertussis (GM 269 U) and greater than those found in 18-month-old children after their fourth dose of diphtheria and tetanus toxoids and pertussis vaccine (GM 20.0 U, p less than 0.001). These data indicate that NICHD-Ptxd is safe and immunogenic in adults, and they justify its evaluation in infants and children.

[Immuno-allergic reactions to cotrimoxazole in a hospital population]. / Reazioni immuno-allergiche a cotrimoxazolo in una popolazione ospedalizzata.

By a study of 87 oncologic hospitalized patients, affected by serious infectious complications and treated with high-dose antibiotic therapy including co-trimoxazole, the authors evaluate the allergic and immunologic reactions to the drug on clinical and serological basis and try to outline the pathogenic implicated mechanisms.

Cellular immunity to vaccinations and herpesvirus infections after bone marrow transplantation.

The cellular immune response to herpesviruses was studied in 46 recipients of marrow grafts (23 autologous, 23 allogeneic). That study was performed in vitro by evaluating the degree of lymphocyte proliferative responses to herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV). No primary infections with any of those viruses were noted after bone marrow transplantation (BMT). The incidence of active infection in seropositive patients was significantly lower after autologous BMT than after allogeneic BMT (HSV, 2/22 vs. 11/22 patients, respectively, P = 0.007; CMV, 4/12 vs. 9/10 patients, respectively, P = 0.02; VZV, 3/23 vs. 11/23 patients, respectively, P = 0.02). After autologous BMT, the restoration of cellular immunity to the three viruses occurred at a clearly faster rate than after allogeneic BMT. That pattern may have contributed to the low incidence of active infections with those viruses after autologous BMT. Recipients of allogeneic marrow from donors with a positive lymphocyte proliferation test to HSV had a significantly increased incidence of active HSV infection post-BMT (8/9 patients) than those who received marrow from donors with a negative test (3/13 patients; P = 0.008). Acute or chronic graft-versus-host disease (GVHD) decreased the cellular immune response to the three herpes viruses, but not significantly. Our program of vaccinations with diphtheria and tetanus toxoids started in the fourth month post BMT. Chronic GVHD patients who were vaccinated had a clearly impaired cellular immune response to both toxoids as compared with those without chronic GVHD.

Dust exposure challenge test as a measure of potential allergenicity and occupational disease risk in handling of Ispaghula products.

It is known that workers in the pharmaceutical industry, and nurses, can become sensitized and develop allergic respiratory symptoms by handling bulk laxatives containing Ispaghula powder. Fifteen individuals allergic to Ispaghula were challenged with a commercially available Ispaghula product and three other products manufactured in a way to make them less dusty. The results show that the use of products with smaller amounts of airborne particles results in a lower incidence of symptoms and thus probably reduces the potential occupational risk of sensitization to the Ispaghula allergen.

Antibody formation to dog pulp tissue altered by camphor paramonochlorophenol via the root canal.

Pulp tissue from three experimental dogs was tested for its antigenicity before and after incubation with CMCP. Reaction to Arthus skin tests showed an increased response to pulp that had been incubated in CMCP, washed, then injected, as compared with pulp or CMCP alone. Hemagglutinating antibody titers (1:360 to 1:450 dilutions) were obtained from pulp tissue altered by CMCP. Inhibition tests showed the specificity of the antibody to be at a dilution titer of 1:350. Therefore, CMCP altered dog pulp tissue and rendered it antigenically active, and a specific humoral response was produced.