Judy Beeler

The influence of HIV-1 exposure and infection on levels of passively acquired antibodies to measles virus in Zambian infants.

BACKGROUNDnThe age at which passively acquired antibodies are lost is critical to determining the optimal age for measles vaccination. Little is known about the influence of human immunodeficiency virus type 1 (HIV-1) infection on levels of prevaccination antibodies to measles virus.nnnMETHODSnAntibodies to measles virus were measured by plaque reduction neutralization assay in HIV-1-infected, HIV-seropositive but uninfected, and HIV-seronegative Zambian infants aged 6 weeks to 9 months. Regression models were used to estimate age-specific antibody concentrations.nnnRESULTSnNeutralizing antibodies to measles virus were measured in 652 plasma samples collected from 448 infants, of whom 61 (13.6%) were HIV-1 infected, 239 (53.4%) were HIV seropositive but uninfected, and 148 (33%) were HIV seronegative. The best fitting model suggests that HIV-1-infected infants have lower levels of passively acquired antibodies to measles virus at birth than do HIV-seronegative infants, but their antibody levels decrease more slowly. By 6 months of age, 91% (95% confidence interval, 83%-99%) of HIV-1-infected infants, 83% (95% confidence interval, 77%-89%) of HIV-seropositive but uninfected infants, and 58% (95% confidence interval, 51%-64%) of HIV-seronegative infants were estimated to have antibody levels that were unlikely to affect immune responses to measles vaccine (cutoff value for immune response, <50 mIU/mL). By 9 months of age, 99% of all infants had antibody levels <50 mIU/mL.nnnCONCLUSIONSnInfants born to HIV-1-infected women are less likely to have passively acquired antibodies that would neutralize measles vaccine virus and, thus, have an increased risk of measles prior to the age of routine vaccination. Protection could be achieved by administration of the first dose of measles vaccine prior to 9 months of age.

Immunogenicity of Standard-Titer Measles Vaccine in HIV-1-Infected and Uninfected Zambian Children: An Observational Study

BACKGROUNDnAchieving 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.nnnMETHODSnWe 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.nnnRESULTSnFrom 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.nnnCONCLUSIONSnAlthough 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.

Kinetics of immunologic responses after primary MMR vaccination

To study the kinetics of humoral as well as cellular immunity to measles and to test for associated immunosuppression 124 12 month old children were studied twice, before routine MMR and either 14, 22, 30, or 38 days after vaccination. Plaque reduction neutralization (PRN) titres were determined at these time points and lymphocytes were evaluated to identify changes in proportions of phenotype, their capacity to generate cytokines and to respond to blast transformation (BT) to measles hemagglutinin (HA), tetanus toxoid and Candida antigen. The PRN titre and BT to HA plateaued at 30 days and CD8+ and NK cells increased after immunization. Interleukin 2, 4, and 10 showed no significant changes. There was mild suppression of BT at 14 and 22 days post-immunization Interferon-gamma was the principal cytokine produced after primary measles immunization, suggesting primary measles immunization induces predominantly a TH1 type response.

Stevens-Johnson syndrome and toxic epidermal necrolysis after vaccination: reports to the vaccine adverse event reporting system.

We conducted a telephone survey of reports of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) to the Vaccine Adverse Event Reporting System. We identified six cases of SJS or TEN after vaccination without other obvious triggers, suggesting that SJS and TEN might very rarely be caused by vaccination. Confirmation of this hypothesis will likely require controlled studies.

Induction of Cellular and Humoral Immunity after Aerosol or Subcutaneous Administration of Edmonston-Zagreb Measles Vaccine as a Primary Dose to 12-Month-Old Children

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.

Measles-Virus–Neutralizing Antibodies in Intravenous Immunoglobulins

Measles infection induces lifelong immunity; however, wild-type infection stimulates higher levels of measles-virus-neutralizing antibodies (mnAbs) than does vaccination. Because the proportion of the donor population with vaccine-induced measles immunity is increasing, this study was conducted to determine whether this shift in demographic characteristics affects mnAb levels in contemporary lots of Immune Globulin Intravenous (Human) (IGIV). When 166 lots of 7 IGIV products manufactured between 1998 and 2003 were assayed by plaque-reduction neutralization test, there was a progressive decrease in geometric mean titers in lots manufactured between 1999 and 2002. IGIV products manufactured from recovered plasma had significantly higher titers than did those manufactured from Source Plasma, which could reflect a change in donor demographic characteristics, because Source Plasma donors tend to be much younger. A reduction in mnAbs also correlated with the loss of either IgG1 and IgG3, possibly because of certain manufacturing procedures, or bivalent antibodies (i.e., intact IgG and F(ab)2), because of fragmentation.

Increasing the Time of Exposure to Aerosol Measles Vaccine Elicits an Immune Response Equivalent to That Seen in 9-Month-Old Mexican Children Given the Same Dose Subcutaneously

BACKGROUNDnA 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.nnnMETHODSnOne 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.nnnRESULTSnAdaptive 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.nnnCONCLUSIONSnIncreasing 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.

Measles Humoral and Cell-Mediated Immunity in Children Aged 5–10 Years After Primary Measles Immunization Administered at 6 or 9 Months of Age

BACKGROUNDnGiven the high infant measles mortality rate, there is interest in whether a measles immunization regimen beginning at <12 months of age provides lasting immunity.nnnMETHODSnMeasles-specific immune responses were evaluated in 70 children aged 5-10 years after primary measles vaccine administered at 6, 9, or 12 months.nnnRESULTSnAt 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).nnnCONCLUSIONSnMeasles-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.

Safety and Immunogenicity of Early Measles Vaccination in Children Born to HIV-Infected Mothers in the United States: Results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 225

UNLABELLEDnBACKGROUND.: 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.nnnMETHODSnPlaque-reduction neutralization (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (∼3 years of age).nnnRESULTSnThe 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).nnnCONCLUSIONSnAmong 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.

Thrombocytopenia after vaccination: case reports to the US Vaccine Adverse Event Reporting System, 1990-2008.

We reviewed thrombocytopenia (TP) reports to the US Vaccine Adverse Event Reporting System (VAERS). We examined TP patterns for differences in single versus multiple immunization reports, presence of a live viral vaccine, seriousness, age, and interval to symptom onset. We found 1510 reports of possible TP and after exclusions evaluated 1440 for possible causes. Most (1078; 75%) met the regulatory definition of a serious adverse event. TP was reported after inactivated and live viral vaccines. Platelet counts <10×10(9)/L were reported. Identified vaccines could be prioritized for hypothesis-testing studies.