Immunogenicity and tolerability of inactivated flu vaccine in high risk and healthy children.

We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe in 154 children between 6 and 36 months of age at high risk of influenza-related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA) antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR) for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP). The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications.

Immunogenicity and tolerability of inactivated flu vaccine In high risk and healthy children / Inmunogenicidad y tolerancia de la vacuna inactivada anti-influenza en niños en alto riesgo y en controles sanos

We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe« in 154 children between 6 and 36 months of age at high risk of influenza- related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA) antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR) for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP). The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications.(AU)

Se realizó un estudio clínico abierto para evaluar la inmunogenícidad y la seguridad de la vacuna inactivada anti-influenza, Imovax Gripe«, en 154 niños entre 6 y 36 meses de edad con alto riesgo de complicaciones ligadas a la influenza, y en un grupo de referencia de 64 niños sanos. El estudio fue conducido en dos temporadas de gripe, durante las cuales la vacuna utilizada contenia las mismas cepas A pero diferentes cepas B. Los resultados para las cepas A/H3N2 y A/H1N1 de las dos temporadas de gripe fueron combinados ( pool de datos), pero no los de las cepas B. Los títulos de anticuerpos anti-hemaglutinina (HA) fueron determinados inmediatamente antes y un mes despues de cada vacunación, y la seguridad o tolerancia fue evaluada según la información de efectos adversos notificados, en cartillas para llenado diario, que incluían todos los eventos, figuraran o no en la lista de los "eventos solicitados". En cada grupo, las tasas de seroconversion y de seroprotección, y la razón de la media geométrica de títulos post-/ pre-vacunación (GMTR) para las cepas A/H3N2 y A/H1N1 cumplieron con todos los requisitos del Comité de Especialidades Farmacéuticas (CPMP) de la Unión Europea. Las respuestas inmunes fueron similares en los niños con alto riesgo y en los sanos, y consistentes con los resultados observados en los estudios anteriores en los niños sanos. La vacuna fue bien tolerada y la reactogenicidad fue baja y similar en los dos grupos de niños estudiados. Las reacciones locales listadas en la solicitud, fueron observadas en el 9.5 a 15.4% y en el 12% de niños con alto riego y sanos respectivamente; mientras que los síntomas sistémicos solicitados fueron observados en el 23.0 a 28.8% y el 25.3% de niños respectivamente. Los resultados de este estudio proveen informatión adicional a favor de la vacunación de niños con alto riesgo de complicaciones relacionadas con influenza.(AU)

Immunogenicity and tolerability of inactivated flu vaccine In high risk and healthy children / Inmunogenicidad y tolerancia de la vacuna inactivada anti-influenza en niños en alto riesgo y en controles sanos

We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe® in 154 children between 6 and 36 months of age at high risk of influenza- related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA) antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR) for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP). The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications.

Se realizó un estudio clínico abierto para evaluar la inmunogenícidad y la seguridad de la vacuna inactivada anti-influenza, Imovax Gripe®, en 154 niños entre 6 y 36 meses de edad con alto riesgo de complicaciones ligadas a la influenza, y en un grupo de referencia de 64 niños sanos. El estudio fue conducido en dos temporadas de gripe, durante las cuales la vacuna utilizada contenia las mismas cepas A pero diferentes cepas B. Los resultados para las cepas A/H3N2 y A/H1N1 de las dos temporadas de gripe fueron combinados ( pool de datos), pero no los de las cepas B. Los títulos de anticuerpos anti-hemaglutinina (HA) fueron determinados inmediatamente antes y un mes despues de cada vacunación, y la seguridad o tolerancia fue evaluada según la información de efectos adversos notificados, en cartillas para llenado diario, que incluían todos los eventos, figuraran o no en la lista de los "eventos solicitados". En cada grupo, las tasas de seroconversion y de seroprotección, y la razón de la media geométrica de títulos post-/ pre-vacunación (GMTR) para las cepas A/H3N2 y A/H1N1 cumplieron con todos los requisitos del Comité de Especialidades Farmacéuticas (CPMP) de la Unión Europea. Las respuestas inmunes fueron similares en los niños con alto riesgo y en los sanos, y consistentes con los resultados observados en los estudios anteriores en los niños sanos. La vacuna fue bien tolerada y la reactogenicidad fue baja y similar en los dos grupos de niños estudiados. Las reacciones locales listadas en la solicitud, fueron observadas en el 9.5 a 15.4% y en el 12% de niños con alto riego y sanos respectivamente; mientras que los síntomas sistémicos solicitados fueron observados en el 23.0 a 28.8% y el 25.3% de niños respectivamente. Los resultados de este estudio proveen informatión adicional a favor de la vacunación de niños con alto riesgo de complicaciones relacionadas con influenza.

Fractal representation of the immune B cell repertoire.

The immune repertoire is characterized by a complex and dynamic organization. Here I suggest, based on the presence of well-defined immune reactivity patterns (RP) analyzed using a linguistic analogy, that the B cell repertoires could possess a fractal structure. A simple estimation method of the fractal dimension (D) for a given immune B repertoire was developed, and D demonstrated to be an useful tool to define what complexity is regarding the immune repertoire, and to evaluate the complexity level of the immune B repertoire among age-structured groups of mice sensitized with the hemagglutinin (HA) molecule of influenza virus. Also, since a fractal-linguistic point of view, considerations are made about the ontogeny, connectivity, chaotic regimes, and size of the immune repertoire. Fractal analysis indicates that the immune repertoire shows a Zipf-like scaling behavior, a statistical property of natural languages. This result suggests that immune repertoire is structured like a powerful language.

Origin and molecular changes associated with emergence of a highly pathogenic H5N2 influenza virus in Mexico.

In October of 1993, there was decreased egg production and increased mortality among Mexican chickens, in association with serologic evidence of an H5N2 influenza virus. First isolated from chickens in May of 1994, after spreading widely in the country, the virus caused only a mild respiratory syndrome in specific pathogen-free chickens. Because eradication of the virus by destruction of infected birds posed major obstacles to the poultry industry in Mexico, we were able to conduct a "field experiment" to determine the fate of an avirulent virus after repeated cycles of replication in millions of chickens. By the end of 1994, the virus had mutated to contain a highly cleavable hemagglutinin (HA), but remained only mildly pathogenic in chickens. Within months, however, it had become lethal in poultry. Nucleotide sequence analysis of the HA cleavage site of the original avirulent strain revealed R-E-T-R, typical of avirulent viruses and unlike the K-K-K-R sequence characterizing viruses responsible for the 1983 outbreak in poultry in the United States. Both mildly and highly pathogenic isolates contained insertions and a substitution of basic residues in the HA connecting peptide, R-K-R-K-T-R, which made the HA highly cleavable in trypsin-free chicken embryo fibroblasts. Phylogenetic analysis of the HA of H5 avian influenza viruses, including the Mexican isolates, indicated that the epidemic virus had originated from the introduction of a single virus of the North American lineage into Mexican chickens. This sequence of events demonstrates, apparently for the first time, the stepwise acquisition of virulence by an avian influenza virus in nature.

Influenzavirus A (H1 N1): algunas características de su hemaglutinina / Influenza A (H1 N1) virus: soe characteristic of its hemagglutinins

Con el retorno a la circulación de los virus de la influenza A (H1N1) en 1978 y la activación del mecanismo de fluctuación antigénica de este subtipo, se hizo necesario estudiar las variantes surgidas, con el fin de comparar sus similitudes y diferencias en estructura antigénica. Por ello se caracterizaron las hemaglutininas de 4 cepas: A/Habana/1292/78 (H1N1);A/Brasil/11/78 (H1N1); A/Chile/1/83 (H1N1) y A/Singapore/6/86 /H1N1) por el método de inhibición de la hemaglutinación. Se estudiaron sus espectros de aglutinación con eritrocitos de diferentes orígenes, el crecimiento a diferentes temperaturas y la sensibilidad a los inhibidores de los sueros de animales. Las hemaglutininas fueron también caracterizadas por anticuerpos monoclonales. Se comprobó que las cepas utilizadas guardan relación antigénica entre sí de una forma u otra

Influenzavirus A (H1 N1): algunas características de su hemaglutinina / Influenza A (H1 N1) virus: some characteristic of its hemagglutinins

Con el retorno a la circulación de los virus de la influenza A (H1N1) en 1978 y la activación del mecanismo de fluctuación antigénica de este subtipo, se hizo necesario estudiar las variantes surgidas, con el fin de comparar sus similitudes y diferencias en estructura antigénica. Por ello se caracterizaron las hemaglutininas de 4 cepas: A/Habana/1292/78 (H1N1);A/Brasil/11/78 (H1N1); A/Chile/1/83 (H1N1) y A/Singapore/6/86 /H1N1) por el método de inhibición de la hemaglutinación. Se estudiaron sus espectros de aglutinación con eritrocitos de diferentes orígenes, el crecimiento a diferentes temperaturas y la sensibilidad a los inhibidores de los sueros de animales. Las hemaglutininas fueron también caracterizadas por anticuerpos monoclonales. Se comprobó que las cepas utilizadas guardan relación antigénica entre sí de una forma u otra

Comparative investigation of the hemagglutinin epitopes of influenza virus A/Brazil/11/78 (H1N1). and its escape variants.

A method described previously for determining the concentration of influenza virus antihemagglutinin antibody molecules, the number of epitopes per virus particle and the equilibrium constant of virus antibody interaction was adapted to the use with escape variants (EVs), produced by multiplication of influenza virus A/Brazil (H1N1) in presence of monoclonal antibody directed to each of the four hemagglutinin sites (Sa, Sb, Ca and Cb). The EVs were found to possess an altered antigenic site, which was both antigenic and immunogenic. By use of selected EVs and antibody preparations, the number of epitopes per antigenic site was determined and it was found that each of the four sites was represented by about 390 epitopes per virus particle, suggesting that each of the about 400 hemagglutinin spikes per virion possessed one epitope of the specificity Sa, Sb, Ca and Cb. Alteration of site Sa but not of site Ca increased the avidity of antibody to react with the unchanged sites.

[Pathogenicity of equine influenza viruses in chickens]. / Patogenicidade dos virus de Influenza equina para pintos.

In the present paper the pathogenicity of equine subtype A/equi 1 (H7N7) and A/equi 2 (H3N8) for chicks was studied. Strains previously isolated in Brazil, representatives of both subtypes, were used. Eight experiments were performed for A/equi 2, using 89 chicks (4 to 18-day old). Six hundred thirty three samples of cloacal material were collected from 01 to 15 days pos-infection (p.i.) and inoculated in 11-day old chick embryos for recuperation of virus. Twelve samples showed positive results. The recuperated viruses were identified with specific antiserum in hemagglutination inhibition test (HI). Blood samples of all chicks collected prior to infection showed no antibodies to both subtypes. Chicks inoculated with A/equi 2 virus were bled 18 to 21 days p.i. Out of 89, seventy one (79.8%) serums showed different levels of antibodies at HI tests. Seventy chicks were inoculated with A/equi 1 subtype. Five hundred forty three samples of cloacal material were harvested and inoculated in embryonated chick eggs. No recuperation of virus occurred. However, all the inoculated chickens showed seroconversion. Chicks infected with A/equi 2 may shed virus in feces. No signs of disease were noted in the inoculated chicks.

Patogenicidade dos virus de influenza equina para pintos / Pathogenicity of equine influenza virus for chickens

Considerando a importância das aves na epidemiologia dos vírus de Influenza tipo "A",procurou-se investigar a patogenicidade para pintos dos vírus de Influenza Equina. Cepas isoladas no Brasil, representativas dos subtipos A/equi 1 (H7N7) e A/equi 2(H3N8), foram usadas. Oito experimentos foram realizados com amostra A/equi 2/RJ/85, utilizando 89 pintos de 04 a 18 dias de idade. Seiscentos e trinta e três amostras de material cloacal, coletadas entre 01 e 14 dias pós-infecçäo (p.i) foram inoculadas em ovos embrionados, ensejando a recuperaçäo de 12 amostras de vírus. Provas de inibiçäo de hemoaglutinaçäo com soros conhecidos mostraram que os vírus recuperados eram inibidos pelos soros imunes homólogos (A/equi 2). O exame dos soros sangüíneos dos pintos usados nestes experimentos, obtidos antes da inoculaçäo de vírus, mostrou ausência de anticorpos para A/equi 1 e A/equi 2. Dos 89 pintos infectados com vírus A/equi 2, o exame dos soros de sangrias realizadas entre 18 e 21 dias p.i. revelou presença de anticorpos para o vírus inoculado em 71 casos (79,8 por cento). Setenta pintos foram inoculados com a cepa A/equi 1; 543 amostras de material cloacal inoculadas em ovos embrionados deram resultados negativos. Entretanto, todos os pintos desenvolveram anticorpos para o vírus inoculado. Näo foi registrado qualquer sinal clínico nos pintos inoculados

[Identification of monoclonal antibodies against protein E1 of venezuelan equine encephalomyelitis virus blocking the hemagglutinating but not the infective activity of virions]. / Identifikatsiia klona antitel k belku E1 virusa venesuél'skogo éntsefalomielita loshadei, blokiruiushchego gemaggliutiniruiushcuiu, no ne infektsionnuiu aktivnost' virionov.

Cellular clone (MAK 14-7), producing antibodies against the virus of Venezuela equine encephalomyelitis (VEE), strain 230, was isolated using the standard hybridomata technology. Monoclonal antibodies neutralized the viral hemagglutinating activity leaving the infectious one intact. Monoclonal antibodies from MAD 14-7 reacted specifically with viral glycoprotein E1 as registered by the immunoprecipitation technique. The topography of antigenic determinants of viral E1/E2 glycoprotein dimer forming the virions outer spikes is discussed in connection with the results obtained.

Rotavirus. I. Hemagglutination and complement fixation inhibitor antibodies in individuals of Mexico city.

Hemagglutination inhibiting antibodies were studied in 1,278 sera of individuals of different ages in Mexico City representative of four different socioeconomic levels. It was found that 1,261 (98.7 per cent) had antibodies against the Nebraska strain (calf rotavirus). An unusual finding was that more than 95 per cent of children from one to four years of age, had antibodies. For this reason five year old children were studied utilizing two viral strains as antigens in hemagglutination inhibition tests. It was found that in 918 sera, 821 (89.4 per cent) had antibodies against SA-11 samples (monkey rotavirus); percentage increased from 87.2 per cent in neonates to 97.5 percent in children from four to five years of age. A similar phenomenon was observed when Nebraska strain hemagglutinin was utilized. Also complement fixation antibodies against SA-11 strain in 583 sera were studied finding that 260 (44.6 per cent) had antibodies. Utilization of this technique showed that seropositivity percentage decreased from 47.6 per cent in the neonate group to 14.5 per cent in the one ot three month old children increasing progressively until reaching 65.1 per cent in children three to four years of age. These results show that rotavirus infection takes place at early ages, as has been confirmed by other authors that have used electron microscopy techniques, RNA electrophoresis, etc., regardless of the presence of transplacental antibodies.

Serum epidemiology of eastern, western and Venezuelan equine encephalitides in Mexico.

The presence of HI antibodies for the Eastern, Western and Venezuelan equine encephalitis was investigated in 16,405 human sera collected in 47 communities in the Mexican Republic. It was found that there is a high percentage of individuals who have antibodies against Venezuelan equine encephalitis. In turn, it was discovered that persons with Western equine encephalitis virus antibodies live in the northwestern states of the country. Very few cases with Eastern equine encephalitis antibodies were detected.