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S A Plotkin

Publications and source records attributed to S A Plotkin.

323 records · Page 18Linked to original sources

Rabies vaccine prepared in human cell cultures: progress and perspectives.

Rabies vaccine prepared in human diploid cell strains is a replacement for the previously available vaccines that are prepared in animal tissues and are less immunogenic and more reactogenic. The human cel-grown vaccine made in the United States is a split-product vaccine, whereas the vaccines made in Europe are whole-virion vaccines. Both types of vaccine contain concentrated and inactivated "fixed" rabies virus. When used before exposure to rabies virus, the vaccine should be given intramuscularly in three 1-ml doses on days 0, 7, and 21. Immediately after exposure to rabies virus, a person should be given human rabies immune globulin (20 international units/kg). This treatment should be followed by five intramuscular doses of vaccine given on days 0, 3, 7, 14, and 28. For maintenance of long-term immunity in persons continously exposed to the risk of rabies, booster doses of the vaccine should be given at two-year intervals.

Animals↗

Acquisition of cytomegalovirus infection among female employees at a pediatric hospital.

Of 842 female employees at a pediatric hospital who were tested for cytomegalovirus antibody, 487 (57.8%) were seronegative. We also studied 228 females who had been employed for 3 or more months, and 139 (61.0%) were seronegative. One year after the initial serum 173 seronegative women provided a second sample. Eleven (6.4%) had seroconverted to cytomegalovirus, and none gave a history of significant illness in the interval. Of the 173 women 138 had patient contact jobs and 35 had noncontact jobs. In the contact group 10 of 138 (7.2%) seroconverted including 5 of 46 (10.9%) intensive care nurses, 2 of 11 (18.2%) women on the blood drawing or intravenous insertion team and 3 of 81 (3.7%) nurses on medical and surgical wards. In the noncontact group 1 of 35 (2.9%) seroconverted. Among female employees at a pediatric hospital the risk of cytomegalovirus is substantial and appears to be related to the type of patient contact.

Cytomegalovirus Infections↗

Diverse serologic response to rotavirus infection of infants in a single epidemic.

Eight infants with onset of gastroenteritis occurring within a 32-day period were examined for stool rotavirus antigen and serum antibody response to rotavirus. Each infant presented evidence of rotavirus infection but no single test for rotavirus-specific antigen or antibody was positive for every infected individual. Rotavirus was identified in the stools of five infants; in the others rotavirus etiology was determined by a specific immune response only. The neutralizing antibody response to each of four human rotavirus serotypes and to bovine rotavirus Nebraska calf diarrhea virus ranged from totally negative to a specific response to up to four serotypes. Three originally seropositive infants each showed an increase in neutralizing antibody titer to two or more serotypes. However, two of five originally seronegative infants also developed antibody to two or more serotypes. No consistent pattern of responses to different serotypes was detected.

Antibodies, Viral↗

Vancomycin pharmacokinetics in infants: relationships to indices of maturation.

The relationships between steady state pharmacokinetics of vancomycin and various indices of maturation were examined in 11 infants (gestational ages, 27 to 40 weeks; postconceptional ages (PCA), 29 to 48 weeks). Vancomycin was administered as a 10-mg/kg iv infusion over 30 minutes. Serial blood samples were obtained over a dosage interval and vancomycin serum concentrations were determined by fluorescence polarization immunoassay. Model-independent pharmacokinetic data analysis yielded values for vancomycin systemic clearance (CL), volume of distribution (Vdss) and half-life ranging from 0.032 to 0.484 liter/hour, 0.44 to 2.5 liters and 3.5 to 9.6 hours respectively. Stepwise multiple regression analysis indicated that PCA was the best single variable model to predict vancomycin clearance as described, namely: CL (liters/hour) = 0.0224 PCA (weeks) - 0.639 (r = 0.91; P less than 0.0001). Other more complex models using a combination of patient variables only modestly improved the ability to explain the variability in vancomycin clearance. Vdss was strongly related to body weight (r = 0.93; P less than 0.0001) Vdss = 0.563 weight (kg) + 0.052). Our results suggest that postnatal alterations in vancomycin disposition are related to maturational changes in body composition and renal function. These data also suggest that vancomycin doses smaller than those previously recommended may be used to achieve therapeutic steady state vancomycin serum concentrations during the first 2 months of life.

Aging↗

Production of RA27/3 rubella vaccine and clinical results with the vaccine.

Adaptation of rubella virus to human diploid cell strains was achieved in 1964, with attenuation in the same cells being accomplished by 1967. The production of rubella vaccine in HDCS is featured by the long period required to build up high titer. High multiplicity of infection gives optimal results. Since rubella virus does not produce a cytopathic effect in HDCS, virus harvests must be made blindly and titrated individually before pooling. A unique feature of this cell-virus relationship is the continuous virus production which takes place for months. For vaccine purposes, however, virus-containing supernatant fluids may be harvested each 48 hrs from the 5th to the 21st day post-infection. Lyophilization presents no particular problems and final titers in ampoules can be as high as 10(5.0) PFU, which represents about 100 subcutaneous doses. Control of rubella vaccine presents only the problem that viral CPE is absent or mild. Therefore the presence or absence of virus may have to be determined by interference. Titration of rubella virus produced in HDCS must be by plaquing in RK13 rabbit kidney cells or by interference in cynomolgus monkey kidney cells. Rubella vaccine (RA27/3 strain) produced in HDCS has been more immunogenic than other strains and retains an ability to infect intranasally as well as subcutaneously.

Antibodies, Viral↗

Cytomegalovirus vaccine prepared in WI-38.

Human fibroblasts are the only cells that regularly produce cytomegalovirus of adapted laboratory strains and release fair amounts of cell free virus. One such strain, Towne, was adapted to WI-38 and could release 10(6) to 10(7) p.f.u. per ml tissue culture fluid. The maximum cell-free virus is released at 5-7 days after infection, when cytopathic effect has reached a peak. The virus harvest must be combined with stabilizer rapidly and rapidly lyophilized or frozen, for the virus is unstable even at 4 degrees C. With regard to control, cytomegalovirus is poorly neutralized by antibody-containing serum, and complement is required for maxium neutralization. Frequent addition of fresh antiserum may be necessary to keep cytomegalovirus from replicating in cells inoculated to detect other viruses. Another special problem is the putative association of oncogenicity with herpes group viruses. Tests must be done in newborn hamsters to show that live or inactivated virus does not cause tumors. Towne vaccine tested in man has produced asymptomatic infection with antibody response. No urine excretion has been observed, and antibodies persist for at least 2 years.

Animals↗

An end to Manicheism.

Although each vaccine has limitations, both OPV and E-IPV have made a considerable contribution to the effective control of polyomyelitis. In view of the complementary advantages of the two vaccines, more use of their association in a common schedule is quite justified. An association of OPV and E-IPV, in which the latter is combined with DTP, seems particularly advantageous immunologically, logistically, and economically. There are several alternative ways in which the two vaccines could be associated sequentially or simultaneously. In addition, each vaccine could be used as a booster for routine programs with the other vaccine.

Diphtheria-Tetanus-Pertussis Vaccine↗