RESUMO
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.
Assuntos
Anticorpos Antivirais/sangue , Vacina contra Sarampo/administração & dosagem , Vacinação , Imunidade Adaptativa , Aerossóis , Feminino , Humanos , Lactente , Interferon gama/biossíntese , Ativação Linfocitária , Masculino , Vacina contra Sarampo/imunologia , México , Linfócitos T/imunologia , Fatores de TempoRESUMO
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.
Assuntos
Anticorpos Antivirais/biossíntese , Vacina contra Sarampo/imunologia , Sarampo/prevenção & controle , Aerossóis , Formação de Anticorpos/imunologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta Imunológica , Feminino , Humanos , Imunidade Celular/imunologia , Imunização , Lactente , Injeções Subcutâneas , Interferon gama/biossíntese , Masculino , Sarampo/imunologia , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/efeitos adversos , México , Linfócitos T/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Ensaio de Placa ViralRESUMO
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.