Longitudinal changes in measles antibody titers in plasma donors and minimum antibody levels of immunoglobulin products for treatment of primary immunodeficiency.

BACKGROUND: To ensure that immunoglobulin (Ig) products have adequate functional antibody, the US Food and Drug Administration (FDA) requires that Ig lots contain minimum levels of measles neutralizing antibody; the current minimum is 0.48 x US Reference Ig 176. STUDY DESIGN AND METHODS: In the first part of the study, measles antibody titers were measured in donor plasma samples collected in 2007, 2011, and 2017. In the second part, trough or steady-state serum levels of measles neutralizing antibody were measured in two studies of patients with primary immunodeficiency (PID) who were treated with intravenous (Study 1; N = 46) or subcutaneous (Study 2; N = 18) Ig replacement therapy, meeting previous requirements for lot potency (≥0.6 x US Reference Ig 176). Serum measles neutralizing antibody titers were then estimated for conditions in which the potency of the Ig replacement product was 0.48 or 0.30 x US Reference Ig 176. RESULTS: Measles antibody titers in donated plasma samples declined in donors born after 1963. In the two studies of patients with PID who were treated with intravenous or subcutaneous Ig replacement therapy, all patients exhibited trough (intravenous Ig) or steady-state (subcutaneous Ig) measles neutralizing antibody titers above 0.12 IU/mL, which has been shown to protect against clinical measles in the general population. Estimates suggest that all patients except one would have continued to meet this standard if the Ig lot potency had been 0.48 or 0.30 x US Reference Ig 176. CONCLUSION: These studies provide supporting evidence that the lot release specification can be safely lowered from 0.48 to 0.30 x US Reference Ig 176, which will accommodate declining measles neutralizing antibody levels in donor plasma.

Measles antibody trough levels after treatment with immunoglobulin products and predicted levels assuming lower measles antibody specifications.

BACKGROUND: Widespread vaccination against measles has resulted in decreasing measles antibody levels in human immune globulin (IG) products. As levels continue to decline, it needs to be determined whether the release specifications for measles antibody levels in IG products can be lowered and still provide protection against infection for patients who receive IG treatment for primary immunodeficiency disease. STUDY DESIGN AND METHODS: Trough level measles neutralizing antibodies were measured in 10 pediatric patients with primary immunodeficiency disease (ages 2-16) treated with IG administered both by intravenous and subcutaneous infusion. The results were used to model worst-case (lowest) serum measles antibody levels in two cases: 1) the current case with intravenous dosage at 300 mg/kg at a measles antibody level of 0.48× Center for Biologics Evaluation and Research Reference 176 and 2) a future case with intravenous dosage at 400 mg/kg and 0.30× Center for Biologics Evaluation and Research Reference 176. RESULTS: Serum trough measles neutralizing antibody levels were an average of 11-fold or greater above minimum protective levels for immunocompetent individuals of 0.12 IU/mL in both the intravenous and subcutaneous phases of the study. Modeling using both the current worst-case dose and future case shows average levels for IG intravenous/subcutaneous infusion of 3.9/4.8- and 3.2/4.0-fold above 0.12 IU/mL for the two cases, respectively. CONCLUSION: Lowering the measles antibody level specification to 0.30× Center for Biologics Evaluation and Research Reference 176 in IG products will still provide trough serum antibody levels against measles infection of greater than 0.12 IU/mL when dosed at 400 mg/kg or higher.

Responses in children to measles vaccination associated with perirenal transplantation.

BACKGROUND: Measles infection can be fatal in pediatric patients with chronic renal failure or in patients who have undergone renal transplantation, both of whom are in the immunosuppressed state. The efficacy of single, live measles vaccination in preventing infection was examined. METHODS: Of 156 children with renal failure who underwent renal transplantation, the changes in antibody titer were investigated before and after renal transplantation in 125 children whose measles antibody titer could be examined, together with disease and vaccination histories. Live measles vaccine was administered to 42 children with negative antibody titer. The antibody seroconversion rate was then investigated in these children, along with rate of antibody maintenance and degree of antibody titer elevation. RESULTS: Seroconversion rate was 97.6%. Antibody titers measured on HI and EIA were 72 +/- 118 fold (HI) and 36.9 +/- 31.3 (EIA), respectively. The geometric mean of the increase in antibody titer 6 months after vaccination was 15. No side-effects of vaccination were observed in any of the children. CONCLUSIONS: Live measles vaccination of children with chronic renal failure is effective and safe, because the seroconversion rate, rate of antibody titer maintenance and degree of antibody titer elevation in children with chronic renal failure were all equivalent to those of healthy children.

Vigilância de síndrome febril exantemática: estudo descritivo de casos com anticorpos da classe IgM contra o sarampo, Estado de São Paulo, 2000 a 2004 / Febrile exanthematic syndrome surveillance: descriptive study of cases with antibody of IgM class anti-measles, State of São Paulo, 2000 to 2004

Objetivo: Descrever os casos de síndrome febril exantemática, identificados no estado de São Paulo entre 2000 e 2004, visando identificar possíveis resíduos de fonte de infecção do sarampo. Métodos: Estudo descritivo. As definições são as utilizadas pelo Plano de Eliminação do Sarampo. O estudo incluiu casos notificados à vigilância da síndrome febril exantemática apresentando anticorpos IgM para sarampo pelas técnicas de ELISA e/ou ELISA de captura. Descreveram-se os aspectos clínicos e epidemiológicos segundo características de tempo, espaço e pessoa. Resultados: Estudaram-se 463 casos possíveis de sarampo; 64,1 por cento e 29,8 por cento foram classificados, respectivamente, como casos expostos e não expostos à vacina; 15,3 por cento apresentaram clínica específica para sarampo e 12,1 por cento apresentaram complicações. Os grupos etários mais representados foram: 9 a 11 meses (36,5 por cento), um ano (32,8 por cento) e cinco anos ou mais (15,2 por cento). A distribuição no espaço e no tempo não sugere a ocorrência de casos relacionados entre si. Entre o final de 2000 e o início de 2002, os casos não expostos à vacina mantiveram-se em patamares elevados, coincidindo com a identificação de dois casos importados de sarampo. Conclusão: as limitações do estudo não permitem análises conclusivas a respeito da circulação de vírus do sarampo no estado de São Paulo, mas o estudo aponta para a necessidade da investigação exaustiva de possíveis resíduos de fontes de infecções entre: menores de nove meses, primo vacinados contra sarampo abaixo de 10 meses, mulheres em idade fértil e casos não expostos à vacina contra sarampo.

Prior infection by respiratory syncytial virus or parainfluenza viruses augments virus-specific IgG responses induced by the measles/mumps/rubella vaccine.

We found previously that immunizing cyclophosphamide-treated mice with one Paramyxoviridae virus mixed with dimethyl dioctadecyl ammonium bromide induces T cells which apparently also recognize other Paramyxoviridae viruses. This finding and the fact that respiratory syncytial virus (RSV) and parainfluenza viruses (PIVs) infect children early in life led us to ask if prior RSV or PIV infections influence the antibody response to measles and mumps vaccine viruses. Detection of virus-specific IgG in serum specimens collected randomly or at defined times after measles/mumps/rubella (MMR) vaccination was done with solid-phase enzyme immunoassays. The antibody-binding data obtained were converted to serum antibody titers by an immunoassay curve-fitting computer program. Prior infection by RSV and PIVs correlated with an augmented IgG response not only to measles and mumps virus, but also to rubella virus. Furthermore, the augmentation was greater for responders below the median response. These data show that common early childhood viral infections can influence immunity induced by the MMR vaccine.

A randomised single blind trial of a combined mumps measles rubella vaccine to evaluate serological response and reactions in the UK population.

Four hundred and twenty children were randomly assigned to receive either mumps measles rubella (MMR) vaccine (207) or measles vaccine (213) in a single blind study, to investigate the reactogenicity and serology of the MMR vaccine. There was no significant difference between the number of children developing symptoms after MMR vaccination to those developing symptoms after measles vaccination. Both vaccines are associated with a rash, temperature and restlessness five to thirteen days after vaccination. The serological response to measles vaccine was similar in both groups with 92-6% seroconverting with MMR, and 96-8% with measles. Seroconvertion against mumps and rubella with the MMR vaccine was 88% and 96% respectively. This study confirms the safety and efficacy of the MMR vaccine in a UK population.

Loss of maternally acquired measles antibodies in well-nourished infants and response to measles vaccination, Peru.

Clinical, anthropometric, and serological evaluations were conducted at birth and at 3, 6, 9, and 10 months (post measles vaccination) in 34 well-nourished Peruvian infants. Seroconversion rate after measles vaccination was 94 percent. The rate of antibody loss was a direct function of birth titer; at age 9 months, all children had identical mean titers regardless of their titer at birth. Differences in maternally acquired measles antibodies at birth were important only during the first six months of life.