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Background: The long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented., Methods: Measles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations., Results: Of 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV-infected children who received two doses of MV at ages 6 and 9 months. Among HIV-uninfected children, protective levels of antibody were found post sMV in 90-99% through ages 24-36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV., Conclusions: Our findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs., (Published by Elsevier Ltd.)

Background: Given the high infant measles mortality rate, there is interest in whether a measles immunization regimen beginning at <12 months of age provides lasting immunity., Methods: Measles-specific immune responses were evaluated in 70 children aged 5-10 years after primary measles vaccine administered at 6, 9, or 12 months., Results: At 5-10 years of age, the stimulation index for measles T-cell proliferation was 11.4 (SE, 1.3), 10.9 (SE, 1.5), and 14.4 (SE 2.1) when the first measles dose was given at 6, 9, or 12 months, respectively. Neutralizing antibody concentration (geometric mean titer [GMT]) in those immunized at 6 months of age was 125 mIU/mL (95% confidence interval [CI], 42-377) in the presence of passive antibodies (PAs) and 335 mIU/mL (95% CI, 211-531) in those without PAs; in those immunized at 9 months, GMTs were 186 mIU/mL (95% CI, 103-335) and 1080 mIU/mL (95% CI, 642-1827) in the presence and absence of PAs, respectively. The GMT was 707 mIU/mL (95% CI, 456-1095) when vaccine was administered at 12 months (P ≤ .04)., Conclusions: Measles-specific T-cell responses were sustained at 5-10 years of age regardless of age at time of primary measles immunization. Neutralizing antibody concentrations were lower in cohorts given the first vaccine dose at 6 months of age and in the presence of PAs; however, responses could be boosted by subsequent doses. Starting measles vaccination at <12 months of age may be beneficial during measles outbreaks or in endemic areas.

Background: Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART)., Methods: HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN). A subset was given another MMR 4-5 years later, and PRN antibody was measured before and 7 and 28 days later., Results: At entry, 52% of 193 subjects were seroprotected (PRN ≥120 mIU/mL). Seroprotection increased to 89% 8 weeks postvaccination, and remained at 80% 80 weeks postvaccination. Of 65 subjects revaccinated 4-5 years later, 85% demonstrated memory based on seroprotection before or 7 days after vaccination. HIV load ≤400 copies/mL at initial study vaccination was associated with higher seroprotection rates, greater antibody concentrations, and memory. Grade 3 fever or fatigue occurred in 2% of subjects., Conclusions: Measles revaccination induced high rates of seroprotection and memory in children receiving HAART. Both endpoints were associated with HIV viral load suppression., Clinical Trials Registration: NCT00013871 (www.clinicaltrials.gov).

Background: A 30-second aerosol measles vaccination successfully primes children 12 months of age and older but is poorly immunogenic when given to 9-month-old children. We examined the immune responses when increasing the duration to aerosol exposure in 9-month-olds., Methods: One hundred and thirteen healthy 9-month-old children from Mexico City were enrolled; 58 received aerosol EZ measles vaccine for 2.5 minutes and 55 subcutaneously. Measles-specific neutralizing antibodies and cellular responses were measured before and at 3 and 6 months postimmunization., Results: Adaptive immunity was induced in 97% after aerosol and 98% after subcutaneous administration. Seroconversion rates and GMCs were 95% and 373 mIU/mL (95% confidence interval [CI], 441-843) following aerosol vaccination and 91% and 306 mIU/mL (95% CI, 367-597) after subcutaneous administration at 3 months. The percentage of children with a measles-specific stimulation index ≥3 was 45% and 60% in the aerosol versus 55% and 59% in the subcutaneous group at 3 and 6 months, respectively. CD8 memory cell frequencies were higher in the aerosol group at 3 months compared with the subcutaneous group. Adverse reactions were comparable in both groups., Conclusions: Increasing exposure time to aerosol measles vaccine elicits immune responses that are comparable to those seen when an equivalent dose is administered by the subcutaneous route in 9-month-old infants.

Waning immunity or secondary vaccine failure (SVF) has been anticipated by some as a challenge to global measles elimination efforts. Although such cases are infrequent, measles virus (MeV) infection can occur in vaccinated individuals following intense and/or prolonged exposure to an infected individual and may present as a modified illness that is unrecognizable as measles outside of the context of a measles outbreak. The immunoglobulin M response in previously vaccinated individuals may be nominal or fleeting, and viral replication may be limited. As global elimination proceeds, additional methods for confirming modified measles cases may be needed to understand whether SVF cases contribute to continued measles virus (MeV) transmission. In this report, we describe clinical symptoms and laboratory results for unvaccinated individuals with acute measles and individuals with SVF identified during MeV outbreaks. SVF cases were characterized by the serological parameters of high-avidity antibodies and distinctively high levels of neutralizing antibody. These parameters may represent useful biomarkers for classification of SVF cases that previously could not be confirmed as such using routine laboratory diagnostic techniques., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.)

Unlabelled: BACKGROUND.: ACTG (Pediatric AIDS Clinical Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus-infected (HIV-infected) (POS) and uninfected (NEG) children in the pre-highly active antiretroviral therapy (pre-HAART) period., Methods: Plaque-reduction neutralization (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (∼3 years of age)., Results: The 110 subjects included: 65 2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n=175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n=2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers ≥120 mIU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mIU/mL, respectively; P=.023). At ∼3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers ≥120 mIU/mL. Prevaccination titers ≥25 mIU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers ≥120 mIU/mL (56% vs 90%; P=.004)., Conclusions: Among HIV-infected children pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

Background: Previously, we demonstrated that measles antibody prevalence was lower at age 12 months among children infected with human immunodeficiency virus (HIV) than uninfected children following measles vaccination (MV) at ages 6 and 9 months. Among HIV-uninfected children, measles antibody prevalence was lower among 1- than 2-dose MV recipients. Here, we report results through age 24 months., Methods: Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to MV at 6 and 9 months or MV at 9 months. We followed children through age 24 months. The child's HIV status was determined and measles immunoglobulin G (IgG) level was measured by enzyme immunoassay (EIA) and by plaque reduction neutralization (PRN) on a subset., Results: Among HIV-uninfected children, the difference in measles antibody prevalence at age 12 months between one- and two-dose recipients reported previously by EIA was shown to be smaller by PRN. By age 24 months, 84% and 87% of HIV-uninfected children receiving 1 or 2 doses, respectively, were seroprotected. Only 41% of 22 HIV-infected children were measles seroprotected at age 20 months., Discussion: Measles seroprotection persisted through age 24 months among HIV-uninfected children who received 1 or 2 doses of MV. HIV-infected children demonstrated seroprotection through age 12 months, but this was not sustained., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.)

Background: Clinical trials of measles vaccination administered as aerosol are planned with the aim of obtaining licensure. Measles antibody levels will be measured using the plaque reduction neutralization test (PRNT) to assess antibody responses as a surrogate marker of efficacy., Methods: A working group examined laboratory protocols for measles PRNT in use at three reference centres and agreed to a standardised procedure, which was subsequently validated., Results: Assay validation showed quantitative results varied approximately threefold both within and between assays. The lower limit of detection was approximately 20milliInternational Units/mL., Conclusions: A standardised laboratory protocol for measles PRNT was established and validated for use in clinical trials of aerosolized measles vaccines.

Background: Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination., Methods: We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka, Zambia., Results: From May 2000 to November 2002, 696 children aged 2-8 months were enrolled. Within 6 months of vaccination, 88% of 50 HIV-1-infected children developed antibody levels of >or=120 mIU/mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P=.3). By 27 months after vaccination, however, only half of the 18 HIV-1-infected children who survived and returned for follow-up maintained measles antibody levels >or=120 mIU/mL, compared with 89% of 71 uninfected children (P=.001) and in contrast with 92% of 12 HIV-1-infected children revaccinated during a supplemental measles immunization activity., Conclusions: Although HIV-1-infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence.

Unlabelled: Aerosol measles vaccination has been found to be more immunogenic than subcutaneous administration as a booster in school aged children, and immunogenic in 12-month-old children as a primary dose. The objective of the study was to evaluate immunogenicity to aerosol measles vaccine in 9-month-old children., Methods: Nine-months-old infants received Edmonston-Zagreb measles vaccine by aerosol (10(3.58) CCID50/0.1 mL, estimated retained dose 10(2.81) CCID50 or subcutaneous route (10(4.28) CCID50/0.5 mL); cellular and humoral immunity and adverse events were assessed., Results: Measles-specific T cell proliferative responses developed in 42% of children given aerosolized vaccine compared with 67% of those who received subcutaneous vaccine (p = 0.01); the mean stimulation index (SI) was 4.4+/-0.7 versus 6.9+/-1, respectively, (p = 0.05). Seroconversion rates were 33 and 92% after aerosol or subcutaneous immunization (p < 0.001). Among infants who developed serologic responses, measles geometric mean titers (GMT; 95% CI) by neutralizing antibody assay were 215 mIU/mL (115-400) in aerosol vaccine recipients and 411 mIU/mL (345-490) in those given subcutaneous vaccine (p = 0.06)., Conclusions: The proportion of 9-month-old infants who developed cellular and/or humoral immunity to measles was lower in the aerosol group but measles antibody and T cell responses were comparable among those who developed measles immunity. Differences in response rates are attributable to the lower aerosol dose. Improving aerosol delivery or increasing the dose may enhance immunogenicity of primary aerosol measles vaccination in this age group.

Infants were immunized by aerosol (10(3.6) plaque-forming units [pfu]/dose) or subcutaneous (sc) (10(4.27) pfu/dose) administration of Edmonston-Zagreb measles vaccine. Measles-specific T cell proliferative responses with a stimulation index of > or =3 developed in 72% of children given aerosol-administered vaccine, compared with 87% given s.c.-administered vaccine (P =.06). Seroconversion rates were 90% after aerosol-administered vaccine and 100% after s.c.-administered vaccine (P=.01), and measles geometric mean titers were 237 milli-international units (mIU) (95% confidence interval [CI], 146-385 mIU) and 487 mIU (95% CI, 390-609 mIU) in each group, respectively (P=.01). Measles-specific T and B cell responses were weaker after aerosol than after sc vaccination, indicating a need to use a higher aerosol dose to achieve optimal immunogenicity.

The objective of this study was to characterize the kinetics of the cellular and humoral immune responses elicited by measles vaccine given to previously immune adults. The cellular and humoral immune responses to measles were measured in seven healthy adults, before vaccination and at 1, 2, 3, and 4 weeks and 3 months after vaccination, using measles-specific T-cell proliferation and plaque reduction neutralization assays. All study subjects had detectable measles antibodies, but only six (85%) showed protective titers, defined as >1:120, before immunization. However measles-specific T-cell proliferation was not detectable before vaccination in any of the subjects. The six subjects with protective titers showed a positive stimulation index (SI) of >3.0 within the first 4 weeks after vaccination, an SI of 5 at the 4th week, and an SI of 3 at 3 months after vaccination. The subject with a low antibody titer (1:99) before vaccination developed a high SI at 3 months after vaccination. This subject was the only participant whose neutralizing antibody titers increased more than 4-fold by 3 months after vaccination. No significant increases in geometric mean titers were detected in the other six subjects during the follow-up period. These data suggest that high measles antibody titers interfere with the humoral response in subjects who receive a booster immunization, whereas the cellular response is boosted at least transiently, after revaccination., (Copyright 2003 Wiley-Liss, Inc.)

Vaccination at 6 months of age followed by routine revaccination is recommended when exposure of infants to measles is likely. Dade County, Florida, began this early two-dose schedule during a large epidemic in 1986–1987 (i.e., 22% of cases occurred in infants aged 6–11 months). This schedule was continued routinely in high-risk areas. The effect of an early two-dose schedule on measles prevention in the county was examined by comparing measles vaccination coverage and epidemiology before (1985–1987) and after (1988–1996) the schedule became routine. To assess serologic response, seroprevalence of measles antibody among children aged 4–6 years in 1995 was examined. To evaluate vaccine effectiveness, a case-control study was conducted among preschool-aged children. Among those aged 2 years, vaccination coverage with ≥1 dose increased from 75% to 94% in 1996. The number of annual cases declined, and endemic measles transmission reportedly ended after 1993. Seroprevalence of plaque reduction neutralization antibody (titer > 1:120) among those receiving vaccination according to an early two-dose schedule and a single dose at age ≥12 months was 94% (95% confidence interval: 89, 98) and 98% (95% confidence interval: 95, 100). In these groups, vaccine effectiveness was comparably high. Early two-dose measles vaccination is associated with improved coverage and a comparably high level of humoral immunity and clinical protection as a single dose at age ≥12 months. This strategy can be useful in areas at high risk for measles among infants. [ABSTRACT FROM PUBLISHER]