Live Measles Vaccine Research Articles

Variability in Immune Response to Pathogens: Using Measles Vaccine to Probe Immunogenetic Determinants of Response

“The measles had not prevailed on the Faroes since 1781; they broke out early in April, 1846. … of the 7,782 inhabitants, about 6,000 were taken with measles … 225 persons in all died … of the many old people still living on the Faroes who had had the measles in 1781, not one … was attacked the second time.” [P. L. Panum, Observations Made during the Epidemic of Measles on the Faroe Islands in the Year 1846]

Outbreak of measles in adults in the north west of Greece.

The overall incidence of measles fell markedly in Greece after measles vaccination was introduced (although precise data are not available), but sporadic outbreaks continue to occur. A live monovalent measles vaccine was introduced in Greece in 1965 and r

Five Cases of Measles Secondary Vaccine Failure with Confirmed Seroconversion after Live Measles Vaccination

We report 5 patients with secondary vaccine failure (SVF) who were infected with natural measles 2, 5, 5, 7 and 12 years, respectively, after vaccination with further attenuated live measles vaccine during infancy. Their seroconversion had been confirmed after vaccination. Three of the 5 patients had mild (modified) measles, while the remaining 2 patients had typical measles. The hemagglutination inhibition antibody titers to measles virus in paired acute and convalescent sera showed a secondary response pattern in 4/5 patients, and a primary response pattern was present in the remaining patient. Measles IgM antibodies were present in all patients during the convalescent stage. The patient with the primary response pattern may have had a decrease in the B cell memory during the 5-year period between vaccination and infection. This may be the first SVF case report that confirms the existence of completely waning immunity in recipients of the further attenuated live measles vaccines.

Polymorphisms of the TAP2 gene may influence antibody response to live measles vaccine virus

The transporter associated with antigen processing (TAP) gene products transport peptides from the cytosol to the endoplasmic reticulum for processing by the immune system. We hypothesized that polymorphisms within the TAP genes may influence measles vaccine antigen processing and hence antibody response. TAP genotypes were determined for subjects who were measles vaccine nonresponders ( n=32) and hyper-responders ( n=28). TAP1 and TAP2 alleles were determined by PCR amplification of specific alleles (PASA). Measles vaccine nonresponders were more likely to be homozygous at TAP2 position 665 than were hyper-responders (OR=5.0, P=0.016). Lastly, a trend was found in the overall distribution of all TAP2 genotype frequencies between hyper-responders and nonresponders ( P=0.08). No association was found between TAP1 polymorphisms and vaccine response. These data reveal an association between TAP2 genotype and measles vaccine antibody response which may explain one mechanism behind vaccine failure.

Immune responses following cocktails of inactivated measles vaccine and Arachis hypogaea L. (groundnut) or Cocos nucifera L. (coconut) oils adjuvant

Haemagglutination inhibition (HAI) geometric mean titre (GMT) and lymphocyte transformation test (LTT) were measured following inoculation of Erythrocebus patas with inactivated measles vaccine (IMV) and oils of Arachis hypogaea L (GO), Cocos nucifera L (CO), Freund's complete and incomplete adjuvants (FCA, FIA). The GMT of HAI were: GO+IMV=8.50±4.15; CO+IMV=8.08±4.03; FCA+IMV=7.67±4.08; FIA+IMV=7.08±4.08 compared with controls of live measles vaccine (LMV)= 7.33±4.33 and IMV=4.33±4.56. The mean stimulation ratio (SR) of lymphocyte transformation data were: GO+IMV=109.69; CO+IMV=58.47; FCA+IMV=55.81; FIA+IMV=55.48; LMV=94.73; IMV=55.64. The results when compared by a two-way multiple pairwise comparison of Tuskey's proceedure at α=0.05 showed that HAI antibody titres were not significantly different in all the groups under investigation. The lymphocyte transformation data for GO+IMV and LMV were identical but significantly different from the other groups. The study suggests that the oils under investigation, particularly the GO oil should be considered as an adjuvant with IMV after extensive study in humans; since it stimulated cellular immune response comparable to that of LMV. This is a promising alternative to the use of LMV in the tropical developing countries with poor storage facilities.

Reduced seroconversion to measles in infants given vitamin A with measles vaccination

Administration of 100000 IU vitamin A at the time of measles immunisation is currently recommended for infants in developing countries. However, the safety and value of giving vitamin A, a potent immune enhancer, with live measles virus vaccines are unknown. We conducted a randomised, double-blind, placebo-controlled clinical trial in Indonesia to evaluate the effect of simultaneous vitamin A supplementation on the immune response to measles immunisation at six months of age. 336 infants received either vitamin A (100000 IU) or placebo when immunised with standard-titre Schwarz measles vaccine. 82% of infants seroconverted to measles. In a multiple logistic regression model adjusting for maternal antibody titres, vitamin A supplementation was associated with a lower likelihood of seroconversion to measles (odds ratio 0.40, 95% Cl 0.19-0.88), and girls were less likely to seroconvert than boys (0.34, 0.15-0.76). Immunisation with standard-titre Schwarz vaccine at six months of age in this study population is characterised by high seroconversion rates. However, simultaneous high-dose vitamin A may interfere with seroconversion to live measles vaccine in infants with maternal antibody.

Is measles vaccination a risk factor for inflammatory bowel disease?

Measles virus may persist in intestinal tissue, particularly that affected by Crohn's disease, and early exposure to measles may be a risk factor for the development of Crohn's disease. Crohn's disease and ulcerative colitis occur in the same families and may share a common aetiology. In view of the rising incidence of inflammatory bowel disease (Crohn's disease and ulcerative colitis), we examined the impact of measles vaccination upon these conditions. Prevalences of Crohn's disease, ulcerative colitis, coeliac disease, and peptic ulceration were determined in 3545 people who had received live measles vaccine in 1964 as part of a measles vaccine trial. A longitudinal birth cohort of 11407 subjects was one unvaccinated comparison cohort, and 2541 partners of those vaccinated was another. Compared with the birth cohort, the relative risk of developing Crohn's disease in the vaccinated group was 3·01 (95% Cl 1·45-6·23) and of developing ulcerative colitis was 2·53 (1·15-5·58). There was no significant difference between these two groups in coeliac disease prevalence. Increased prevalence of inflammatory bowel disease, but not coeliac disease or peptic ulceration, was found in the vaccinated cohort compared with their partners. These findings suggest that measles virus may play a part in the development not only of Crohn's disease but also of ulcerative colitis.

Measles vaccine: a 27-year follow-up.

In 1964, the Medical Research Council undertook a trial of measles vaccine in over 36,000 United Kingdom children; 9577 of whom received live vaccine, 10,625 received inactivated followed by live vaccines, and 16,328 acted as unvaccinated controls. Participants in this study have been followed to determine the long term protection from measles vaccine and follow-up data were available on 4194, 4638 and 274 respectively. During the 5-year period 1986-90, the protective efficacy of live measles vaccine has remained high at 87%, but the 95% confidence interval was wide (-43 to 99%) due to the small numbers of cases. Between 1976 and 1990, however, the overall efficacy of the live vaccine was 92% (95% confidence interval 86 to 95%) and there was no evidence of a decline in efficacy (P = 0.13) over the 15-year period. This study suggests that the protection from live measles vaccine persists for up to 27 years after vaccination, and that no change in the current United Kingdom measles immunization policy should be made on the grounds of waning immunity.

Sex differences in the humoral antibody response to live measles vaccine in young adults.

Following vaccination of children using high-titre live measles vaccine, excess non-specific mortality was reported, particularly among females. Since vaccination with live measles virus results in a temporary depression of the immune response to other antigens, the female predominance in subsequent non-measles mortality may be due to sex differences in response to live measles vaccines. In this study, the immunogenicity of standard titre live Schwarz strain measles vaccine was examined 2 and 4 weeks post-vaccination in 223 males and 66 female aged 18-20 years in Israel in 1991. Females had higher post-vaccination geometric mean titre (GMT) at all levels of pre-vaccination titres at both 2 and 4 weeks. Furthermore, after controlling for differences in pre-vaccination titres, overall the post-vaccination GMT for females was about 50% higher than for males (P < 0.001). These findings indicate that females exhibit a stronger humoral immune response to measles vaccine. Possible sex differences in immunosuppression following measles vaccination should be explored.

A European Collaborative Study to Assess the Proficiency of Laboratory Estimates of Potency of Live Measles, Mumps and Rubella Tri-valent Vaccines

Abstract. A collaborative study involving 10 European laboratories was undertaken to assess the variability of estimates of the potency of measles, mumps and rubella tri-valent vaccines. The precision of assays as demonstrated by tests on duplicate samples was good; differences averaged around 0·2 log 10 steps. Similarly, assay to assay variation within laboratories was small with most achieving consistency around 5% over three assays. In contrast, overall median variations in potency between laboratories were around 1·0 log 10 for measles, 3·0 log 10 for mumps and 2·0 log 10 for rubella. Unexpectedly, the variations in estimates for measles and rubella were not improved when potencies were expressed relative to reference preparations. However, for mumps variability was reduced by using a reference but only for the vaccines of the same strain as the reference. For these Urabe mumps vaccines the variation in relative potency was around 1·5 log 10.

Molecular cloning and complete nucleotide sequence of genomic RNA of the AIK-C strain of attenuated measles virus

Twelve cDNA clones covering the entire genome of the AIK-C strain of a seed for live measles vaccine were obtained, and the nucleotide sequences were determined. The full viral genomic RNA consists of 15,894 nucleotides. Comparisons of the nucleotide sequence and the deduced amino acid sequence between the AIK-C and other Edmonston strains revealed the following changes: 56 nucleotide differences and one C residue insertion, 31 amino acid changes, and 19 silent mutations.

A collaborative study to assess the proficiency of laboratory estimates of potency of live measles vaccines

A collaborative study was undertaken to assess the variability in estimates of the potency of measles vaccines. Overall a median variation of 2·0 log 10 between estimates was observed. This was reduced to a median of 1·0 log 10 when the potencies were expressed relative to a reference vaccine. A difference in the sensitivity between plaque assays and TCID 50 assays was also reduced when relative potencies were used. The benefit of including a common reference preparation in vaccine assays was therefore demonstrated. For the vaccines assayed in this study, it was not necessary to use a measles reference of the same strain as the vaccines tested. We therefore recommend that measles vaccines be assayed against a single international reference preparation.

Child mortality after high-titre measles vaccines: prospective study in Senegal

The use of Edmonston-Zagreb high-titre (EZ-HT) vaccine at age 6 months has been recommended for countries in which measles before the age of 9 months is a substantial cause of death, but little is known about the long-term effects of high-titre live measles vaccines given early in life. In a randomised vaccine trial in a rural area of Senegal, children were randomly assigned at birth to three vaccine groups: EZ-HT at 5 months (n=336); Schwarz high-titre (SW-HT) at 5 months (n=321); and placebo at 5 months followed by standard low-titre Schwarz vaccine at 10 months (standard: n=358). All children were prospectively followed for 24-39 months in a well-established demographic surveillance system. Child mortality after immunisation was significantly higher in the two groups which received high-titre vaccines than in the group given the standard vaccine. The relative risk of death was 1·80 (95% confidence interval [CI] 1·18-2·74; p=0·007) in the EZ-HT group and 1·51 (0·97-2·34; p=0·07) in the SW-HT group compared with the standard group. The three vaccine groups were comparable as regards various social, family, and health characteristics, and there was no difference in mortality between children who received the standard vaccine and those who were eligible for the trial but did not take part for various reasons. The higher risk of death in the two high-titre vaccine groups remained significant in multivariate analyses. These findings suggest a need to reconsider the use of high-titre measles vaccines early in life in less developed countries.

A measles outbreak at a college with a prematriculation immunization requirement.

In early 1988 an outbreak of 84 measles cases occurred at a college in Colorado in which over 98 percent of students had documentation of adequate measles immunity (physician diagnosed measles, receipt of live measles vaccine on or after the first birthday, or serologic evidence of immunity) due to an immunization requirement in effect since 1986. To examine potential risk factors for measles vaccine failure, we conducted a retrospective cohort study among students living in campus dormitories using student health service vaccination records. Overall, 70 (83 percent) cases had been vaccinated at greater than or equal to 12 months of age. Students living in campus dormitories were at increased risk for measles compared to students living off-campus (RR = 3.0, 95% CI = 2.0, 4.7). Students vaccinated at 12-14 months of age were at increased risk compared to those vaccinated at greater than or equal to 15 months (RR = 3.1, 95% CI = 1.7, 5.7). Time since vaccination was not a risk factor for vaccine failure. Measles vaccine effectiveness was calculated to be 94% (95% CI = 86, 98) for vaccination at greater than or equal to 15 months. As in secondary schools, measles outbreaks can occur among highly vaccinated college populations. Implementation of recent recommendations to require two doses of measles vaccine for college entrants should help reduce measles outbreaks in college populations.

Adult immunizations

There are good data to recommend routine use of vaccines against measles, rubella, tetanus, influenza, and pneumococcal infections in adults. An adolescent or an adult born after 1956 is considered to be susceptible to measles unless he or she has received two doses of live measles vaccine or has suffered a physician-diagnosed case of measles. Tetanus is largely a disease of the elderly, and there is a universal need for immunizations with tetanus toxoid. Influenza continues to be a major public health problem, and influenza vaccine should be given annually to the elderly and to those at high risk. The efficacy of pneumococcal vaccine in American adults is still being debated. Results from case-control studies show that the vaccine is about 60% effective in reducing the incidence of disease due to vaccine-related strains. Its use in the elderly and in those at higher risk for pneumococcal infection is recommended.

Personal and Family History of Seizures and Measles Immunization

A recent analysis of reports of reactions following measles immunization has revealed that children who had seizures following measles vaccine were more likely to have a personal history of seizures or a history of seizures in siblings or parents than vaccinees who had nonneurologic reactions associated with immunization.1 These seizures usually are associated with fever and occur five to 11 days postimmunization when febrile reactions to live measles virus are most common; approximately 5% to 15% of vaccinees have elevated temperatures during this time. The seizures resemble typical febrile seizures which are common at this age and are rarely associated with any sequelae. In one study, the vast majority of children who had seizures following live measles vaccination had temperature elevations and about half were associated with intercurrent infections.2 The Committee strongly recommends that children who have a personal or family history of seizures should receive live measles vaccination. Seizures are unpleasant experiences but the risk of measles to unimmunized children is far more significant. Outbreaks in schools with as few as 5% of the children seronegative have been reported.3 Thus, live measles vaccine should not be denied these children. The parents of children who have either a personal or a family history of seizures should be advised of the risk and told in advance of immunization what they should do if the child does indeed have a seizure. Because the period of risk is approximately 1 week, it is difficult to recommend an effective method of decreasing the chances of seizure occurring.

HUMAN IMMUNODEFICIENCY VIRUS INFECTION AND ROUTINE CHILDHOOD IMMUNISATION

Current experience with the safety and efficacy of vaccines in infected children and adults is reviewed to examine the basis for decisions about routine immunisations of children infected with the human immunodeficiency virus (HIV). No adverse reactions to inactivated vaccines have been noted, but complications with live vaccines have been recorded with both BCG and smallpox. Limited experience with live poliomyelitis and measles vaccines in HIV-infected children has not yet shown any severe complications from these vaccines. Theoretical concerns that immunisation might accelerate the course of HIV infection are not supported by available data. Serological response to most inactivated and live vaccines is reduced in HIV-infected persons, and is related to the degree of immunosuppression present. Preliminary evidence suggests that the severity of some vaccine-preventable diseases is increased in HIV-infected children. This review finds general support for recommendations on immunisation of HIV-infected children that have been developed by the World Health Organisation.

Measles outbreak in a fully immunized secondary-school population.

An outbreak of measles occurred among adolescents in Corpus Christi, Texas, in the spring of 1985, even though vaccination requirements for school attendance had been thoroughly enforced. Serum samples from 1806 students at two secondary schools were obtained eight days after the onset of the first case. Only 4.1 percent of these students (74 of 1806) lacked detectable antibody to measles according to enzyme-linked immunosorbent assay, and more than 99 percent had records of vaccination with live measles vaccine. Stratified analysis showed that the number of doses of vaccine received was the most important predictor of antibody response. Ninety-five percent confidence intervals of seronegative rates were 0 to 3.3 percent for students who had received two prior doses of vaccine, as compared with 3.6 to 6.8 percent for students who had received only a single dose. After the survey, none of the 1732 seropositive students contracted measles. Fourteen of 74 seronegative students, all of whom had been vaccinated, contracted measles. In addition, three seronegative students seroconverted without experiencing any symptoms. We conclude that outbreaks of measles can occur in secondary schools, even when more than 99 percent of the students have been vaccinated and more than 95 percent are immune.

Humoral antibody responses to biannual multiantigen vaccination: report of a field trial on children in Sudan

One hundred and sixty-six children aged 3-30/12 were enrolled in this study. Initially all children were given a single injection containing live measles vaccine, diphtheria and tetanus toxoids, inactivated polio vaccine and meningococcal, A & C polysaccharide, plus an intradermal injection of BCG. In a second visit 6 months later each child was tuberculin tested and given a second dose of all the above vaccines with the exception of BCG. Blood samples were obtained before and 1 month after each vaccination. Following the second dose there was satisfactory seroconversion for all the vaccines. Tuberculin positivity rose from 5.4% before BCG vaccination to 94.4% 6 months after its administration. It is concluded that it is safe and effective to give these antigens simultaneously and that this particular schedule lends itself for use with nomadic and other unaccessible groups of population.

Long-term antibody response after measles vaccination in an isolated arctic society in Greenland.

Scoresbysund is an isolated district on the east coast of Greenland with 500 inhabitants, mainly Polar Eskimos, which had never been exposed to natural measles. In 1968 more than 90% of the population were vaccinated with the Schwarz live further-attenuated measles vaccine and subsequently children born after 1968 likewise received the measles vaccination. Upon the initial measles vaccination no clinical cases of measles have been observed. The immunity status of the isolated population has been followed for 16 years after vaccination by IgM, IgA, and IgG ELISA tests and by HI test on a series of serum samples taken at intervals. Immunoblotting was performed on sera obtained 16 years after the vaccination. In general, antibody studies have demonstrated some decline in antibody titres after the initial measles vaccination. However, a temporary moderate increase in measles antibodies occurred in some individuals 2-4 years after vaccination, probably due to a reinfection of vaccinees. Most of these individuals did not have demonstrable IgA antibodies prior to the supposed reinfection.