Cellular Immunity in Measles Vaccine Failure: Demonstration of Measles Antigen-Specific Lymphoproliferative Responses despite Limited Serum Antibody Production after Revaccination

Abstract

Measles antigen-specific immune responses were evaluated 1 and 6 months after revaccination in 60 previously vaccinated subjects (9.4 +/- 3.4 years of age) who had either undetectable or low plaque reduction neutralization (PRN) titers (< 200). PRN titers were increased in all subjects at 1 month (590 +/- 61; range, 129-2513) but fell again in 66% of subjects by 6 months (214 +/- 29; range, 30-794). At 6 months, 23 (38%) had subprotective (< 120) or borderline (< 200) PRN titers. Lymphoproliferative responses to measles virus antigens were low overall before revaccination (mean stimulation index [SI], 2.6 +/- 0.4; range, 0.5-13.5) but were readily detectable at 1 (SI, 145.8 +/- 2.6; range, 1.4-80) and 6 months after revaccination (SI, 9.4 +/- 1.8; range, 1.1-87). Before revaccination, 10 of the subjects (50%) with low positive PRN titers had SIs > or = 3. At 6 months after revaccination, 18 subjects (78%) with PRN titers < or = 200 had SIs > or = 3. These data suggest that cellular responses to measles virus may be better sustained than antibody titers after vaccination and revaccination in some subjects.

Neonatal Immunization with a Sindbis Virus-DNA Measles Vaccine Induces Adult-Like Neutralizing Antibodies and Cell-Mediated Immunity in the Presence of Maternal Antibodies

“…Although vaccine-induced PRN Abs are deemed essential to block virus entrance to the host cell, T cell responses can control viral replication and confer protection, as demonstrated in vaccinated monkeys upon MV challenge (12,15,59,60). The contribution of CMI to preventing measles infection in humans in the light of "failed" seroconversion has been increasingly recognized (31,32,55,61,62). Experiments to investigate the protective efficacy of our MV DNA vaccines in very young infant rhesus macaques are underway.…”

Frequency of Measles Virus-Specific CD4+and CD8+T Cells in Subjects Seronegative or Highly Seropositive for Measles Vaccine

“…3 H]thymidine incorporation assay as previously described with slight modifications (4,34). Cells were washed twice in RPMI 1640 and resuspended at a concentration of 2 ϫ 10 5 /0.1 ml of complete RPMI 1640, supplemented with penicillin-streptomycin (100 U/ml), 5% fetal horse serum (Sigma, St. Louis, Mo.…”

“…), and the results were expressed as stimulation indices (SI), which is a ratio of mean counts per minute of antigen-stimulated cells to counts per minute of unstimulated cells. Stimulation indices of Ն3 were considered to be positive (4,34).…”

“…Preferential activation of interleukin-4 (IL-4)-producing Th2 cells by measles vaccine has been reported previously in response to measles immunization, which may lead to a lack of long-lasting immunity post-measles vaccination (35). Although humoral immunity plays a pivotal role in protection against measles, several reports suggest that CMI is essential for recovery from measles and may be sufficient for long-term immunity (13,18,20,32,34). This is best illustrated in children with isolated agammaglobulinemia who recover from measles and develop lifelong immunity to measles (15).…”

Age for Routine Administration of the Second Dose of Measles–Mumps–Rubella Vaccine

“…13 The measurement of cell-mediated immunity is impractical for large scale studies; therefore, the response to measles-containing vaccine usually is determined by measuring humoral immunity. In 1989, primary vaccine failure, a failure to seroconvert after vaccination, and secondary vaccine failure, loss of immunity over time, seemed to contribute to the outbreaks of measles.…”