RESUMO
Se evaluó la inocuidad, inmunogenicidad y eficacia de una vacuna tetravalente obtenida por recombinación genética de rotavirus aislados de monos rhesus y seres humanos (RRV-TV) (4 x 104 unidades formadoras de placas por dosis) en un ensayo prospectivo, aleatorio, a doble ciego y controlado con placebo que se efectuó con 540 lactantes brasileños. Se administraron dosis de vacuna o de placebo a la edad de 1, 3 y 5 meses. No se observaron diferencias significativas en la frecuencia de diarrea o vómito en los bebés de ninguno de los dos grupos después de administrar la dosis correspondiente. De 2 a 3% de los vacunados tuvieron fiebre baja los días tercero a quinto después de recibir la primera dosis, pero no después de las dosis segunda o tercera. Se observó una respuesta de anticuerpos del tipo IgA al rotavirus aislado de monos rhesus (RRV) en 58% de los vacunados y en 33% de quienes recibieron placebo. La respuesta de anticuerpos neutralizantes a cada serotipo no pasó de 20% cuando se determinó con la prueba de reducción de focos de fluorescencia, pero fue superior a 40% al medirse con la prueba de neutralización a base de reducción de placas. Se presentaron 91 casos de diarrea causada por rotavirus entre los niños que recibieron las tres dosis (de vacuna o de placebo) durante un seguimiento de 2 años, 36 de ellos en los niños vacunados. La eficacia general de la vacuna fue de 8% (P = 0,005) contra toda clase de diarrea y de 35% (P = 0,03) contra la diarrea causada por rotavirus. La protección durante el primer año de seguimiento, cuando predominó el rotavirus G del serotipo 1, fue de 57% (P = 0,008), pero se redujo a 12% en el segundo año. Se obtuvieron resultados similares al restringir el análisis a episodios en que el rotavirus fue el único agente patógeno identificado. Se observó en la vacuna una mayor tendencia a proteger contra casos de enfermedad con un promedio de seis o más deposiciones diarias. Estos resultados son lo suficientemente...
A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 104 plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages, 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 35 in 23% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.
Assuntos
Vacinas contra Rotavirus/imunologia , Imunogenicidade da Vacina/genética , Imunogenicidade da Vacina/imunologia , BrasilRESUMO
A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4) plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.
Assuntos
Infecções por Rotavirus/prevenção & controle , Rotavirus/imunologia , Vacinas Virais/normas , Animais , Anticorpos Antivirais/isolamento & purificação , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Humanos , Recém-Nascido , Macaca mulatta , Estudos Prospectivos , Rotavirus/classificação , Infecções por Rotavirus/imunologia , Sorotipagem , Vacinas Virais/imunologiaRESUMO
A prospective study of acute diarrhoeal diseases was carried out from April 1990 to September 1992 with the purpose of assessing the immunogenicity, safety and efficacy of a Rhesus-human reassortant rotavirus ("RRV-TV") vaccine, involving 540 children living in Belém, Pará, Brazil. As half of the children received placebo, this trial provided the opportunity of broadening the knowledge on both clinical and epidemiological aspects of rotavirus infection in the Amazon region. There were 2,789 diarrhoeal episodes during the above mentioned period, of which 86 (3.1%) associated with rotavirus; serotype 1 was the more prevalent, accounting for 67.9% of serotyped strains. Rates of 5.9 and 0.2 episodes of diarrhoea per child/year were noted for all cases and the rotavirus-related ones, respectively. This agent was the only pathogen found in 70.9% of the 86 rotavirus-related episodes of acute diarrhoea, whereas the most frequent associations involved Giardia intestinalis and enteropathogenic Escherichia coli, accounting for 7.0% and 11.6% of mixed infections,respectively. The monthly rates of rotavirus-related episodes of diarrhoea ranged from 0.8% to 9.6%, reaching the highest peaks during the dry months of the year. Means of clinical severity scores of 9.4 and 5.3 were recorded for the rotavirus-related episodes of diarrhoea and those of other aetiology, respectively.
