Immune response to measles vaccine in Peruvian children.

OBJECTIVE: To evaluate the immune response in Peruvian children following measles vaccination. METHODS: Fifty-five Peruvian children received Schwarz measles vaccine (about 10(3) plaque forming units) at about 9 months of age. Blood samples were taken before vaccination, then twice after vaccination: one sample at between 1 and 4 weeks after vaccination and the final sample 3 months post vaccination for evaluation of immune cell phenotype and lymphoproliferative responses to measles and non-measles antigens. Measles-specific antibodies were measured by plaque reduction neutralization. FINDINGS: The humoral response developed rapidly after vaccination; only 4 of the 55 children (7%) had plaque reduction neutralization titres <200 mlU/ml 3 months after vaccination. However, only 8 out of 35 children tested (23%) had lymphoproliferative responses to measles antigens 3-4 weeks after vaccination. Children with poor lymphoproliferative responses to measles antigens had readily detectable lymphoproliferative responses to other antigens. Flow cytometric analysis of peripheral blood mononuclear cells revealed diffuse immune system activation at the time of vaccination in most children. The capacity to mount a lymphoproliferative response to measles antigens was associated with expression of CD45RO on CD4+ T-cells. CONCLUSION: The 55 Peruvian children had excellent antibody responses after measles vaccination, but only 23% (8 out of 35) generated detectable lymphoproliferative responses to measles antigens (compared with 55-67% in children in the industrialized world). This difference may contribute to the less than uniform success of measles vaccination programmes in the developing world.

Development and durability of measles antigen-specific lymphoproliferative response after MMR vaccination.

The correlates of long-term protection from measles infection are poorly understood. We followed the development of measles-specific antibody and lymphoproliferative (LP) responses in 60 children for 6 months after MMR vaccination. Prevaccine plaque reduction neutralization antibody (PRN Ab) values were low (mean+/-SEM 9.9+/-1. 1). Ninety-three percent (56/60) had excellent PRN values at 6 months (PRN 1816+/-207). Prevaccine LP activity was also low (stimulation index (SI)=1.4+/-0.1) but increased rapidly (SI 10. 7+/-4.5 at 2-3 weeks; p<0.05). However, only 61% (37/60) of the children had both significant cellular and antibody responses (SI>/=3 and PRN>/=120: Ab(hi)CMI(hi)). One child had a strong LP response (SI=6.7) despite little antibody production (PRN=19 at 6 months: Ab(lo)CMI(hi)). We also conducted a cross-sectional study in a separate group of 87 children 5-13 years after MMR vaccination. PRN values >/=120 were present in most children at 5-8 (n=28) and 9-13 years (n=59) after vaccination (PRN 550+/-120 and 360+/-60, respectively) but a significant minority had either undetected or 'subprotective' values (29 and 34%, respectively). LP responses (SI>/=3) were detectable in 19/28 (66%) and 36/59 (56%) of the children 5-8 and 9-13 years after vaccination (SI 11.4+/-2.4 and 7. 75+/-1.9, respectively). Almost two thirds (18/28) of the children in the cross-sectional study with low or absent antibody titers (PRN 41+/-6) had strong LP responses to measles antigens (SI 6.8+/-1.3). These data suggest that LP responses may be better sustained than antibody titers in some children. The susceptibility of Ab(lo)CMI(hi) children to infection and the value of the early LP response for predicting the durability of immunity remain to be determined.

Measurement of measles virus-specific neutralizing antibodies: evaluation of the syncytium inhibition assay in comparison with the plaque reduction neutralization test.

Plaque reduction neutralization (PRN) is the "gold-standard" for the measurement of measles-specific neutralizing antibodies. However, it is a complicated assay and tends to be operator-dependent. It has been suggested that the simpler syncytium inhibition assay (SIA) can give results comparable to the PRN test. We compared these two assays using 594 serum or plasma samples obtained from children at various times after natural infection, primary measles immunization, and measles revaccination. The results of the two assays correlated well overall (r = .86; p < 0.0001). The strain of challenge virus (wild-type versus vaccine strain) did not significantly influence SIA titers and the assay performed equally well with serum and plasma. PRN titers > or = 120 and > 800 are thought to indicate protection against clinical illness and infection respectively. The equivalent SIA cut-off values using 125 plaque-forming units as the challenge inoculum were > or = 16 and > 128 respectively. At low PRN titers (< 200), the correlation between PRN and SIA values was reasonable (r = 0.60; p < 0.001) when a challenge inoculum of 12.5 plaque-forming units was used. At the lowest PRN titers (< 100), 15% of the samples gave divergent results. These data confirm the utility of the SIA in the determination of measles-specific neutralizing antibodies when antibody titers are high. However, the PRN assay remains the test of choice when maximum sensitivity at low titers is required.