Immunization of Six-Month-Old Infants with Different Doses of Edmonston–Zagreb and Schwarz Measles Vaccines

Abstract

Because measles causes an estimated 2 million deaths per year among children in developing countries, including a substantial proportion of infants less than nine months old--the age at which vaccination is recommended--there has been interest in using different strains of vaccine and higher doses to achieve immunization of younger infants. We conducted a randomized trial of three different doses of Edmonston-Zagreb and of Schwarz measles vaccines in infants to evaluate the effect of the strain and dose of vaccine on the serologic response and acute adverse reactions to vaccination. Six-month-old infants received a standard, medium, or high dose of one of the vaccines, and nine-month-old infants received a standard dose. Antibody levels were measured before and after vaccination, by means of a plaque-reduction neutralization assay, in 1061 six-month-olds and 299 nine-month-olds. Edmonston-Zagreb vaccine produced higher rates of seroconversion and seropositivity than comparable doses of Schwarz vaccine. Among the six-month-old infants, the seroconversion rate 18 weeks after vaccination with the standard dose of Edmonston-Zagreb vaccine was 92 percent, that with the medium dose was 96 to 97 percent, and that with the high dose was 98 percent; the rates for the corresponding doses of Schwarz vaccine were 66 percent, 76 percent, and 91 percent, respectively. Higher seroconversion rates were observed with an increase in the dose of either Edmonston-Zagreb (P less than 0.01) or Schwarz (P less than 0.001) vaccine. The seroconversion rates produced by high and medium doses of Edmonston-Zagreb vaccine in six-month-olds were equal to or significantly higher than the rate produced by a standard dose of Schwarz vaccine in nine-month-olds (87 percent). Clinical adverse reactions were not associated with the strain or dose of a vaccine. We conclude that Edmonston-Zagreb vaccine is more immunogenic than Schwarz vaccine in infants and can induce effective immunization against measles at six months of age.

A Seroepidemiological Study of Measles: Some Practical Implications for Measles Immunization Program, Kingdom of Saudi Arabia

“…Though there was a higher rate of seroconversion following Edmonston-Zagreb vaccination (90.18%), no statistically significant difference with Schwartz vaccine (88.48%) was found (Z=1.01, P>0.01) in the surveyed population. The higher immunogenicity produced by Edmonston-Zagreb strain has been documented in various researches, 24,25 only in this context the design of our study and schedules of measles vaccination might have resulted in incongruous findings. The strengths of this study are the clinically confirmed diagnosis of measles, relatively large sample of measles patients, combination of clinical sample with community-based normal population explored for current immunological status and finally, data so derived from two sources supporting each other.…”

Human Parainfluenza Virus Type 3 (PIV3) Expressing the Hemagglutinin Protein of Measles Virus Provides a Potential Method for Immunization against Measles Virus and PIV3 in Early Infancy

“…By using another approach, the measles vaccine virus was administered parenterally at a 10-to 100-fold-increased dose (38). This improved seroconversion in infants 4 to 6 months of age, but there was an associated increase in mortality in the high-titer vaccine recipients later in infancy (22,28,38).…”

“…The goal of such a vaccine would be the elimination of measles disease that occurs within the first year of life as well as that which occurs thereafter. Given this need, there have been numerous attempts to develop an immunization strategy to protect infants in the latter half of the first year of life against measles virus, but an immunization strategy to protect the 6-to 12-month-old infant has not emerged (2,12,19,20,35,38,42,47,51,58,64,65) (see Discussion).…”

Generation of a More Immunogenic Measles Vaccine by Increasing Its Hemagglutinin Expression

“…Clinical trials revealed a dosedependent, statistically significant increase in seroconversion with increasing measles vaccine titers (9), thus demonstrating that the increased immunogenic stimulus of the higher-titer vaccine was sufficient to overcome barriers to MV immunization in young infants. Although efficient, the use of high-titer MV vaccines was withdrawn following observations of increased mortality rates not related to wild-type MV infection in female recipients (10-14; reviewed in reference 15).…”