Live measles vaccine prepared in dog kidney cells. 3. Vaccination against measles with Czechoslovak live vaccine.
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Two groups of six-week-old beagle puppies were vaccinated with either high titre canine distemper virus or human measles virus, a third group remaining unvaccinated. All the puppies were subsequently challenged by the nasopharyngeal route at 10 weeks old with the virulent Snyder-Hill strain of canine distemper. Severe clinical signs were observed in 90 per cent of the unvaccinated dogs but both groups of vaccinated dogs survived the challenge. High temperatures were recorded in 20 per cent of the measles vaccinates and abdominal petechial rashes were observed in 60 per cent of them. The only clinical signs observed in the puppies vaccinated with distemper virus were transient rashes in 20 per cent of the group. The high titre canine distemper vaccine stimulated a humoral response quickly in 78 per cent of the puppies in the presence of maternally derived antibody and protected them against challenge with the virulent Snyder-Hill strain of distemper virus. The remaining dogs responded sluggishly but were still protected against challenge. The results of field surveys showed that 95 per cent of young puppies with different levels of maternally derived antibodies responded to the distemper component in a vaccine also containing canine parvovirus. No incompatibility was observed between the two components.
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BACKGROUND: Previous studies have suggested that standard measles vaccine may reduce mortality by more than the number of deaths thought to be caused by measles infection in areas with high mortality. However, these observations have not been based on randomized trials. METHODS: During the recent war in Guinea-Bissau, most children fled from the city of Bissau and immunization services in the country broke down for several months. We were performing a trial in which children were randomized at 6 months of age to receive either measles vaccine or inactivated polio vaccine. Because of the war many children did not receive the dose of measles vaccine planned for 9 months of age. We were able to monitor mortality during the war and after. RESULTS: Included in the study were 433 children 6 to 11 months of age. Fifteen children died (3.6%) during the first 3 months of the war before vaccination programs were resumed, 4 of 214 measles-vaccinated children and 11 of 219 children who had received inactivated polio vaccine. The effect of measles vaccine was marked for girls [mortality rate ratio (MR), 0.00; 95% confidence limits, 0.0 to 0.37], whereas there was no difference for boys (MR = 1.02; 95% confidence limits, 0.25 to 3.88). In a combined analysis controlling for factors that differed between the two groups, the MR for measles-vaccinated children was 0.30 (95% confidence limits, 0.08 to 0.87). Prolonging the period of observation to the end of 1998 or including the prewar period did not modify the significant beneficial effect of measles vaccine for girls. Twenty-two of the children in the cohort were reported to have had measles, 8 cases occurring during the 3 months of the war. Exclusion of measles cases in the analysis did not change the results; children who had received measles vaccine had a MR of 0.28 (95% confidence limits, 0.06 to 0.89) during the first 3 months of the war. CONCLUSIONS: Consistent with previous observational studies, measles vaccination was associated with a reduction in mortality that cannot be explained by the prevention of measles infection. This nonspecific beneficial effect was particularly strong for girls. Further studies are needed to examine the extent of nonspecific effects in settings with high mortality.
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The authors discuss the possibility of intranasal revaccination with live measles vaccine. Intranasal vaccination is no less effective than subcutaneous. It induces generalized immune response and formation of anti-measles IgA in the nasopharyngeal mucosa. Immunomodulating side effects of intranasal vaccination are less pronounced than those of subcutaneous one. The intranasal method of vaccination is safer than the inhalation method, which involves exposure of the bronchial mucosa to the live measles virus. The efficiency of mucosal measles vaccine can be increased by adding this or that adjuvant to the vaccine.
Measles vaccine is widely used, most often in association with mumps and rubella vaccines. We report here the case of a child presenting with fever 8 days after vaccination with a measles-mumps-rubella vaccine. Measles virus was isolated in a throat swab taken 4 days after fever onset. This virus was then further genetically characterised as a vaccine-type virus. Fever occurring subsequent to measles vaccination is related to the replication of the live attenuated vaccine virus. In the case presented here, the vaccine virus was isolated in the throat, showing that subcutaneous injection of an attenuated measles strain can result in respiratory excretion of this virus.
In none of the examined children, regardless of whether they manifested negative (17 children) or positive (25 children) seroconversion after vaccination with live measles vaccine, interferon activity could be demonstrated in the serum (starting with 1:4 dilution) withdrawn at the time of the vaccine administration.
BACKGROUND: Measles kills more than 1 million infants per year and is particularly lethal in infants < 1 year old in developing countries. Recent reports have suggested that measles vaccines of different strains and titre differ in their immunogenicity in young infants. We sought to identify strains and titres of measles vaccines which would be effective in 6 and 9 month old infants. METHODS: We conducted a randomized trial of AIK-C, Edmonston-Zagreb (EZ), Leningrad-16 and Schwarz strains of measles vaccine at different titres in 1202 6 month old and 1250 9 month old infants. Antibody levels were measured by haemagglutination inhibition assay. Seroconversion was defined as a change from seronegative to seropositive or a fourfold rise in titre above the expected level after antibody decay (assumed antibody half-life = 6 weeks). Chi-square tests were used to compare seroconversion rates and rates of adverse reactions among the groups. Comparison of geometric mean titres (GMT) was done by the Student's t-test. RESULTS: No severe or unusual adverse reactions occurred during the 6 weeks after vaccination. All strains induced high seroconversion rates in 9 month old infants. In 6 month olds, medium- and standard-titre AIK-C induced the highest rates of seroconversion. Antibody titres at 6 weeks after vaccination were highest in recipients of Schwartz vaccine and lowest for EZ vaccine recipients. CONCLUSIONS: Standard-titre AIK-C may be more effective than other measles vaccine strains for early measles immunization and should be evaluated further for efficacy, long-term immunogenicity, and long-term safety.
Most strategies for reducing global measles morbidity and mortality and eliminating measles are based on the ability to enhance immune responses to measles virus. Challenges to measles elimination and eradication are based in part on the need to sustain high levels of population immunity to interrupt transmission of measles virus. We review aspects of the immunology of measles and measles vaccination with the aim of demonstrating how knowledge of the immune responses is essential to furthering the goals of reducing measles morbidity and mortality and the elimination of measles. Better understanding of the mechanisms of immune suppression after measles, the potential for alternative vaccination strategies to induce immunity in young infants, and the immunologic basis of atypical measles, increased mortality after high-titer measles vaccine, and waning immunity will lead to improved strategies for measles control and elimination.
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Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.
Seven measles virus (MV) strains were isolated from children who developed clinical signs of fever and rash 3-9 days after measles vaccination. The nucleotide sequence of the H gene, the molecular size of the H protein, the haemadsorption activity on African green monkey red blood cells, and antigenicity as determined by virus neutralization revealed that one strain was of the vaccine type and the remaining six were the wild virus type. Isolation of the virus directly from patients suspected of a vaccine-induced side-reaction and subsequent characterization of such isolated virus may be useful in differentiation between vaccine-induced side-reactions and natural measles.
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