Arlene A. McLean

Live attenuated varicella virus vaccine. Efficacy trial in healthy children.

We conducted a double-blind, placebo-controlled efficacy trial of the live attenuated Oka/Merck varicella vaccine among 956 children between the ages of 1 and 14 years, with a negative clinical history of varicella. Of the 914 children who were serologically confirmed to be susceptible to varicella, 468 received vaccine and 446 received placebo. The vaccine produced few clinical reactions and was well tolerated. There was no clinical evidence of viral spread from vaccinated children to sibling controls. Approximately eight weeks after vaccination, 94 per cent of the initially seronegative children who received vaccine had detectable antibody to varicella. During the nine-month surveillance period, 39 clinically diagnosed cases of varicella, 38 of which were confirmed by laboratory tests, occurred among study participants. All 39 cases occurred in placebo recipients; no child who received vaccine contracted varicella. The vaccine was 100 per cent efficacious in preventing varicella in this population of healthy children (P less than 10(-9).

Vaccination and Revaccination with Polyvalent Pneumococcal Polysaccharide Vaccines in Adults and Infants

Summary Adult persons developed substantial antibody increases against essentially all pneumococcal capsular types following injection of polyvalent pneumococcal vaccine containing 50 μg of each capsular polysaccharide per dose. Revaccination 13 months after the previous immunization did not evoke important further increases in antibodies and there was substantially greater local reaction at the injection site than when the previous dose was given. This finding appeared due to local reaction of antigens with circulating antibodies in the area of injection, since there was a correlation between the measured amount of circulating pneumococcal antibodies and the degree of reaction. Infants less than 2 years of age who were given a half-dose of vaccine generally responded poorly when compared with adults. In studies of 3- to 5-month-old infants, there was some increase _in antibodies when a booster dose of vaccine was given 6 months after the first. Very high level antibody responses against all capsular types were obtained when revaccination was delayed until 2 years of age.

Studies in Human Subjects of Polyvalent Pneumococcal Vaccines

Summary Clinical studies of 12- and 14-valent pneumococcal capsular polysaccha-ride vaccines were carried out among 76 adults and 42 children. All but a small proportion of persons developed significant increases in homologous antibody against all capsular types in the vaccine. Clinical reactions consisted mostly of mild fever and self-limiting local reactions at the injection site, such as commonly seen following administration of killed vaccines. Antibody persisted remarkably well with only slight decline 20 months after the vaccine was given. The vaccine shows great promise for preventing disease and death caused by pneu-mococci and merits wide discretionary application. The authors are greatly indebted to L. Gorkum, M.D., E. McNicholas, M.D., and G. A. Starkweather, M.D., and to J. Campbell, R.N., K. W. Campbell, R.N., B.S., and J. Laughead, R.N., for professional medical and nursing assistance. V. Holmes, B.S., B. Last, G. Lowden, A.B., M.S., and J. Staub, B.S., provided important technical assistance.

Clinical and Laboratory Studies of Combined Live Measles, Mumps, and Rubella Vaccines Using the RA 27/3 Rubella Virus

Abstract Eleven lots of combined bivalent and trivalent vaccines containing the measles (Moraten), mumps (Jeryl Lynn), and rubella (RA 2713) viruses gave satisfactory results in tests in initially seronegative children (measles, 493 children; mumps, 377; rubella, 586). There was no apparent suppression of antibody response against any of the viruses in the vaccines. The clinical reactions observed were mild and inconsequential. Substitution of the HPV 77-DE strain employed heretofore with the RA 27/3 is technically acceptable and offers the advantage of higher titer, slightly greater seroconversion rate, and more solid immunity against reinfection in nature.

Clinical and laboratory studies of live cytomegalovirus vaccine Ad-169.

Summary Live strain Ad-169 vaccine was prepared in human diploid cell strain WI-38 and studied clinically in 43 adult male priests and seminarians. All seronegative persons who were vaccinated developed antibody, and the immune adherence and neutralizing antibodies persisted at high levels for at least one year. Clinical reactions were minor consisting mainly of soreness, induration, and erythema at the injection site and mild systemic reaction including headache, chills, fatigue, myalgia, and fever in a few persons. It was not possible to recover virus from the peripheral leukocytes, urine, or throat of seronegative persons who were vaccinated. Susceptible persons who were in contact with the vaccinated persons failed both to excrete virus and to develop antibody indicating lack of contagious spread of the vaccine virus. Continuing investigations to measure the safety and efficacy of the vaccine seem highly justified in view of the importance of the virus in fetal damage, transfusion disease, and organ transplantation.

Stability on storage at various temperatures of live measles, mumps and rubella virus vaccines in new stabilizer.

Dried live measles, mumps and rubella virus vaccines prepared in a new stabilizing medium were tested for loss of potency, according to time, at a range of temperatures from −20°C to 54–56°C. All vaccines proved remarkably stable and predictive values for retention of adequate potency for periods of time at a range of temperatures are presented. The quality of the current vaccine should go far toward assuring potency under adverse conditions of handling in developed countries and in handling outside the cold chain in emerging parts of the world.

Pneumococcal vaccine: dose, revaccination, and coadministration with influenza vaccine.

Summary Current pneumococcal vaccine contains 14 specific capsular polysaccharide antigens, each in 50-γg amount. Reduction of dosage to 25 or 12.5 γg per type gave reduced antibody responses in human subjects for most of the serotypes and these were less than current requirements of the U.S. Food and Drug Administration. Specific antibody following vaccination declines slowly and there was no worthwhile increase in antibody on revaccination 1 to 1.5 years following prior vaccination. Reduction in the dosage of antigen to one-half or one-fourth the 50 γg per antigen amount eliminated the enhanced local and systemic reactions noted previously when the full vaccine amount was given but the time interval between vaccination and revaccination was not long enough to test for the ability of the reduced dose to restimulate antibody production. Pneumococcal and influenza virus vaccines given at the same time into opposite arms showed no important reduction in antibody response to either vaccine and there was no increase in local or systemic reactions compared with that found when the vaccines were given alone.

Persistence of antibody in human subjects for 7 to 10 years following administration of combined live attenuated measles, mumps, and rubella virus vaccines.

Abstract Antibody persistence was measured in children in the open community 10.5 years after combined measles-mumps-rubella (14 children), 9 years after measles-rubella (17 children), 10.5 years after mumps-rubella (9 children), and 7 years after measles-mumps (20 children) vaccines were given. There were increases, declines, and stationary titers among the children in the serum samples taken 6 weeks after vaccination compared with those taken at later time periods. This reflected a decline in antibody in some children and subclinical natural reinfection in others. Importantly, all the children still retained detectable antibody, indicating long-term persistence of immunity by vaccination with combined virus vaccines.

Seroepidemiologic investigations of human hepatitis caused by A, B, and a possible third virus.

Summary Seroepidemiologic studies were made of normal subjects in populations in the United States and Costa Rica and in family outbreaks of hepatitis in Costa Rica. Hepatitis A affected a majority of children of very young age in Costa Rica, while such experience in persons of high socioeconomic status in the United States did not occur before middle life. Persons of low socioeconomic status (paid plasma donors) and residents and attendants of institutions for the mentally retarded showed a far greater incidence of hepatitis A antibody than did their counterparts in the open community. Hepatitis A and B epidemics occurred in families in Costa Rica with rapid spread to other susceptible members of the group. The disease was clinically apparent in roughly half the cases, whether the responsible agent be hepatitis A or B. Five cases of nonhepatitis A or B (hypothetical hepatitis C) were found and all but one of them were subclinical. The authors are indebted to M. A. Chacón, D. Jimenez E., and A. Rivas E. and to P. Giesa, L. Hoover, W. P. M. Fisher, and M. Johnston for valuable technical assistance.

Persistence of Pneumococcal Antibodies in Human Subjects following Vaccination

Abstract Adult persons who were given a pneumococcal polysaccharide vaccine containing 50 μg each of 12 serotypes showed an average 10-fold increase in amount of antibody to the 12 antigens (range 6- to 20-fold) 1 month after vaccination and there was an approximate average 50% decline in antibody 31/2 years later. Children who were 2 to 12 years old at the time of vaccination showed about the same antibody response to the vaccine but this was less persistent and there was about a 55% decline, on the average, after only 21 months, The findings are discussed in the light of need for revaccination and of the nature of antibody responses to polysaccharide antigens.