Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil

Abstract The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines.In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18–60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed.A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults.The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Qiangzhi decoction protects mice from influenza A pneumonia through inhibition of inflammatory cytokine storm / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the preventive effects of Qiangzhi Decoction (, QZD) on influenza A pneumonia through inhibition of inflammatory cytokine storm in vivo and in vitro.</p><p><b>METHODS</b>One hundred ICR mice were randomly divided into the virus control, the Tamiflu control and the QZD high-, medium-, and low-dose groups. Mice were infected intranasally with influenza virus (H1N1) at 10 median lethal dose (LD50). QZD and Tamiflu were administered intragastrically twice daily from day 0 to day 7 after infection. The virus control group was treated with distilled water alone under the same condition. The number of surviving mice was recorded daily for 14 days after viral infection. The histological damage and viral replication and the expression of inflammatory cytokines were monitored. Additionally, the suppression capacity on the secretion of regulated on activation normal T cells expressed and secreted (RANTES) and tumor necrosis factor-α (TNF-α) in epithelial and macrophage cell-lines were evaluated.</p><p><b>RESULTS</b>Compared with the virus control group, the survival rate of the QZD groups significantly improved in a dose-dependent manner (P<0.05), the viral titers in lung tissue was inhibited (P<0.05), and the production of inflammatory cytokines interferon-γ (IFN-γ), interleukin-6 (IL-6), TNF-α, and intercellular adhesion molecule-1 (ICAM-1) were suppressed (P<0.05). Meanwhile, the secretion of RANTETS and TNF-α by epithelial and macrophage cell-lines was inhibited with the treatment of QZD respectively in vitro (p<0.05) CONCLUSIONS: The preventive effects of QZD on influenza virus infection might be due to its unique cytokine inhibition mechanism. QZD may have significant therapeutic potential in combination with antiviral drugs.</p>

Caracterización biológica de tres aislamientos naturales del Rubulavirus porcino (México)

Biological characterization of three natural isolates of the porcine rubulavirus (Mexico). Porcine rubulavirus (PoRV) produces a neurological and reproductive syndrome in pigs called the blue-eye disease, known only from Mexico. Several isolates were grouped by the main symptoms presented during outbreaks: a) neurotropic in piglets, b) broadly neurotropic in piglets and gonadotropic in adults, and c) gonadotropic in adults. We studied some biological properties of three strains, which fall in one of each virus group: La Piedad Michoacán (LPM) and Producción Animal Cerdos 1 (PAC1) and 3 (PAC3), respectively. The analyzed viral properties are mainly related with the trans-membrane hemagglutinin-neuraminidase (HN) and fusion (F) proteins, such as cytopathic effect, hemolysis, hemagglutinating (HA) and neuraminidase (NA) activities. In the infection assays PAC1 strain presented the highest fusogenicity level; however, the most cytolytic strain was PAC3. In addition, HA and NA activities and viral genome of PAC3 strain was detected in supernatants during cell infection earlier than in the other two strains, which shows that PAC3 virions release from the host cell earlier than LPM and PAC1. Experimental determination in purified viruses shows that PAC3 presented a higher HA and NA activities; however, PAC1 shows other interesting properties, such as a high thermostability of HN and differences about substrate profile respect to LPM and PAC3. Our data suggest that NA activity is associated with the virulence of RVP. Rev. Biol. Trop. 56 (2): 487-499. Epub 2008 June 30.

El Rubulavirus porcino causa un síndrome neurológico y reproductivo en cerdos, hasta ahora reportado sólo en México. Los virus aislados se agrupan de acuerdo con los síntomas principales observados durante los brotes en: a) neutrópicos en lechones, b) neurotrópicos en lechones/gonadotrópicos en adultos y c) gonadotrópicos en adultos. En este trabajo se estudiaron tres cepas: La Piedad Michoacán (LPM) y Producción Animal "Cerdos" 1 (PAC1) y 3 (PAC3), ubicadas respectivamente en cada grupo. Las propiedades estudiadas se relacionan principalmente con dos proteínas de la envoltura viral, la hemaglutinina-neuraminidasa (HN) y la proteína de fusión (F). Se cuantificaron el efecto citopático y las actividades de hemólisis, hemaglutinación (HA) y neuraminidasa (NA). En cultivo celular la cepa PAC1 presentó una mayor actividad fusogénica, sin embargo PAC3 presentó la mayor actividad citolítica. La cepa PAC3 fue la primera en ser detectada en sobrenadante de células infectadas (HA, NA y genoma), lo que muestra que sus viriones son liberados al medio antes que las otras dos cepas. PAC3 tuvo las actividades más altas de HA y NA, sin embargo, PAC1 presentó una mayor termoestabilidad en estas actividades de HN y un perfil de substrato algo distinto de los observados para LPM y PAC3. Estos datos sugieren que la actividad de NA está relacionada con la virulencia del RVP.

Vigilancia seroepidemiológica de los Parainfluenza virus humano (PIVh) tipos 2 y 3 en una población infantil seleccionada en Ciudad de La Habana / Seroepidemiological surveillance of human parainfluenza viruses (HPIVs) types 2 and 3 in an infantile population selected in Havana City

Se estudió la presencia de anticuerpos contra los virus Parainfluenza humanos tipos 2 y 3 en 1 793 sueros de una población infantil menor de 14 años de edad. Para el pesquisaje de las muestras clínicas se empleó como sistema la técnica de inhibición de la hemaglutinación. Del total de sueros analizados fueron positivos 1 382 (77,1 por ciento), de estos se confirmó la presencia de anticuerpos contra el tipo 2 en 320 (17,8 por ciento), para el tipo 3 en 334 (18,6 por ciento) y predominó la seropositividad simultánea en 805 (44,9 por ciento). Se constató la circulación de los virus Parainfluenza humanos durante todos los meses del año y en todos los grupos de edades analizados, con aumento en los porcentajes de positividad con la edad

Red blood cell elution time of strains of Newcastle disease virus

Elution time of velogenic, mesogenic and lentogenic strains of Newcastle disease virus was determined. The differences in their elution time were also calculated. Four samples, each of a velogenic strain (VGF2), a mesogenic strain (Komarov) and a lentogenic strain (LaSota) were used for hemagglutination test with 0.6% chicken red blood cells. The time it took for wells of the end hemagglutination points (highest dilution that gave agglutination) to elute was recorded as elution time for each sample. The mean elution time of the three strains of Newcastle disease virus differed significantly (p < 0.05). The velogenic strain gave the highest mean elution time of 118 min, followed by the mesogenic strain with 59 min and the lentogenic strain with 25 min. Based on this result it appears that elution time could form a basis for rough characterization of isolates of Newcastle disease virus into the three major strains.

Viremic blood donor found by a rapid screening method in a season of high human parvovirus B19 activity in Niterói, Rio de Janeiro, Brazil

Erythrovirus B19 infection is usually benign but may have serious consequences in patients with hemolytic anemia (transient aplastic crisis), immunodeficiency (in whom persistent infection can lead to chronic bone marrow failure with anemia), or who are in the first or second trimester of gestation (spontaneous abortion, hydrops fetalis, and fetal death). Being non-enveloped, B19 resists most inactivation methods and can be transmitted by transfusion. B19 is difficult to cultivate and native virus is usually obtained from viremic blood. As specific antibodies may be absent, and there is no reliable immunological method for antigen detection, hybridization or polymerase chain reaction are needed for detecting viremia. A rapid method, gel hemagglutination (Diamed ID-Parvovirus B19 Antigen Test), can disclose highly viremic donations, whose elimination lessens the viral burden in pooled blood products and may even render them non-infectious. In order to obtain native antigen and to determine the frequency of viremic donors, we applied this test to blood donors in a period of high viral activity in our community. Positive or indeterminate results were re-tested by dot-blot hybridization. We tested 472 donors in 1998 and 831 ones in 1999. One viremic donor was found in 1999. We suggest that in periods of high community viral activity the gel hemagglutination test may be useful in avoiding highly viremic blood being added to plasma pools or directly transfused to patients under risk.

A passive haemagglutination test for rabies antibodies using rabies glycoprotein coupled erythrocytes.

The presently recommended tests for assaying rabies antibodies like mouse neutralization test (MINT) and rapid fluorescent focus inhibition test (RFFIT) are either time consuming or expensive and are generally performed in reference laboratories. There is a need to develop a specific and rapid method for detection of rabies antibodies that can be used to monitor sero-conversion after pre-or post-exposure vaccination. In this study, we have developed a passive haemagglutination (PHA) using purified rabies virus glycoprotein coupled to sheep erythrocytes using chromium chloride (0.04%) as a coupling agent. Two hundred and fifty five serum samples from people vaccinated with different rabies vaccines, 16 paired serum and CSF samples from autopsy confirmed cases of paralytic rabies, and serum samples from 65 normal healthy controls were tested and evaluated in comparison to standard MNT. Among the vaccinees, 250 samples were positive both by MNT and PHA but 5 samples were negative by PHA and positive by MNT. The titres obtained by PHA were lower compared to MNT, but there was significant correlation between the two (r=0.885). The specificity of the test was 99.7% and sensitivity was 100% as compared to MNT. Thus this PHA test promises to be a rapid and specific test for assaying rabies antibodies and may be useful in screening large number of serum samples for sero conversion after vaccination. It may also assist in rapid laboratory confirmation of paralytic rabies cases, based on detection of antibodies in CSF and serum.

Transplacental transfer of measles antibody in Delhi.

OBJECTIVE: To find out the patterns of and the factors, if any, affecting the transplacental transfer of measles antibody. DESIGN: Comparison of measles antibody titres in mothers with titres in cord blood samples. METHODS: Maternal and cord blood samples from 174 full-term pregnant women of middle socio-economic status were tested for hemagglutination inhibition (HI) antibody against measles in Delhi during October 1993 to January 1995. None of the mothers had been immunized against measles. RESULTS: Antibody were undetectable in both maternal and cord samples in only 4 (2.3%) pairs. Mean maternal titre was found to be 2.94 Log2. Transplacental concentration and dilution were respectively observed in 34% and 26% of the samples. Cord titres were more often higher than the maternal values only if the maternal values were low. Overall, cord/maternal ratio of mean titre (Log2) was found to be 1.06. Although the age of the mother and parity had had no significant bearing on the transplacental transfer of measles antibody, cord titres were significantly more often higher than the maternal values as the birth weight increased (Chi-square for linear trend = 5.4; p = 0.02). CONCLUSIONS: The study failed to show appreciable concentration of measles antibodies across the placenta.

Levantamento sorológico de parvovírus bovino no rebanho leiteiro do RS, Brasil / Serological survey of bovine parvovirus in dairy herds of Rio Grande do Sul State, Brazil

Para determinaçäo da prevalência de animais com anticorpos contra o parvovírus bovino (BVP), e avaliaçäo do nível de imunidade do rebanho leiteiro do Estado do Rio Grande do Sul (RS), foram testadas 4.096 amostras de soro de bovinos. Os animais eram de diferentes idades e provenientes das diversas bacias leiteiras do Estado. As amostras foram examinadas pela técnica de inibiçäo da hemaglutinaçäo. Do total analisado, 4.000 (97,7 por cento) mostraram anticorpos inibidores da hemaglutinaçäo, sendo 2.715 (66,3 por cento) com títulos de anticorpos entre 1:160 e 1:5120. Näo se observou correlaçäo entre idade e título de anticorpos dos animais. As bacias leiteiras n§ 3 (representada pela regiäo de Bagé) e 6 (representada pelos municípios de Erexim e Tapejara, dentre outros) apresentaram animais com os mais altos títulos de anticorpos e a bacia n§ 7 (representada pelos municípios de Colorado, Espumoso, Selbach e Tapera, dentre outros) com os mais baixos títulos. Concluiu-se que o BVP está amplamente disseminado no rebanho leiteiro do RS e pode ser o agente determinante de diarréia neonatal ou de problemas respiratórios e reprodutivos, apesar da maioria dos animais apresentarem alto grau de imunidade humoral contra o vírus

The role of antigenically different virus neuraminidases as structures implicated in receptor-binding processes

Influenza A viruses exhibit segmented nucleic acid coding for eight different proteins, two of them as glycoproteins exposed on their lipoprotein envelopes, hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin exhibits recptor-binding activity while neuraminidase develps sialidase cleavage activity which acts on cell receptors. Influenza A strains responsible for human, avian, equine and porcine respiratory infections all over the world present antigenically different hemagglutinin (H1 to H14) and neutraminidase (N1 to N9) structures on their surface. The objective of the present investigation was study the role of N2, N8 and N9, anti-genically diverse neuraminidase structures of human (N2) and animal (N8 and N9) influenza viruses, in the receptor-binding process. REceptor-binding activity of N2 and N8 was anlyzed by crossed tests using H3N2 and H3N8 antisera and the hemagglutination inhibition test as a model. Hemangglutinating activity of antigenically different N2 and N8 structures was demonstrable and was inhibited by homologous antisera (N2-H3N2, N8-H3N8) but not by heterologous antisera (N2-H3-N8,N8-H3-N2). This previously demonstrated N9 hemagglutinating activity was analysed for receptor-binding specificity using hemagglutination test and NeuAc alpha2,3Gal and NeuAc alpha2,6Gal derivatized erythrocytes. This highly purified N9 strain was obtained from a virus strain isolated from terns by Dr. Peter Colman (CSIRO Division of Biomolecular Engineering, Parkville, Victoria, Australia)...

Effects of low pH on hemagglutinating and hemolytic activities of west equine encephalomyelitis virus

1. The hemagglutinating (HA) and hemolytic (HL) activities mediated by egg-propagated west equine encephalomyelitis (WEE) virus preparations were investigated. 2. The purified virus preparation exhibited the best HA and HL activity at pH 6.0 and 6.0-6.2, respectively, as observed in the HA and HL tests. 3. In the virus preparations, both HA and HL activities were completely lost upon pretreatment at low pH (6.0). 4. The present results suggest that the alphavirus-mediated HA and HL activities against chicken erythrocytes can be considered to be a fusion from without

Anticuerpos contra el virus de la encefalitis equina venezolana en la población humana del Distrito Mara del Estado Zulia. Venezuela / Antibodies against venezuelan equine encephalitis virus in the human population of Distrito Mara Estado Zulia. Venezuela

Con el propósito de conocer la presencia de anticuerpos contra el virus de la Encefalitis Equina Venezolana, en la población humana del Distrito Mara, Estado Zulia, Venezuela, se tomaron entre junio, julio y septiembre de 1988, 239 muestras de sangre. Estas provenían de las poblaciones de San Rafael de Mara (78), Santa Cruz de Mara (69), Carrasquero (33), 4 Bocas-La Sierrita (33), Isla de San Carlos (7) e Isla de Toas (19). Las muestras fueron ordenadas de acuerdo al sexo y edad. De los sujetos estudiados, 89 fueron menores de 15 años y 150, de 15 años y más. Utilizando el método de inhibición de la hemaglutinación, se encontró que del total de muestras, 224 resultaron negativas, representando un 93,7%. Quince tuvieron títulos superiores a 1:20, lo que representó solo un 6,3% de positividad. De estos resultados se desprende que la mayoría de la población estudiada no tenía anticuerpos contra el vitus de la Encefalitis Equina Venezolana, sobre todo los niños nacidos después de la última epidemia ocurrida en 1973, lo cual representa un alerta sobre la situación inmunológica de la población de este Distrito en relación a este virus, y que en cualquier momento puede originarse una nueva epidemia

Anticuerpos contra el virus de la encefalitis equina venezolana en la población del Distrito Páez del Estado Zulia, Venezuela / Antibodies against Venezuelan Equine Encephalitis virus in the population of Zulia State, Venezuela

Con el proposito de conocer la presencia de anticuerpos para el virus de la Encefalitis Equina Venezolana (EEV), se estudiaron 192 sueros (112 niños y 80 adultos), provenientes de las poblaciones de Carretal, Cojoro, Paraguaipoa (Dtto. Páez), entre los meses de Marzo y Octubre de 1986. Las muestras fueron analizadas mediante las técnicas de inhibición de la hemaglutinación (IHA), usando antígeno de EEV (cepa guajira). Se encontró que de las 192 muestras procesadas, 161 fueron negativas, para un 84%; esta ausencia de anticuerpos se observó principalemte, en la población infantil donde alcanzó un 97%. La negatividad en los adultos fue de 65%. Estos resultados demuestran que no ha habido actividad viral desde la última epidemia de 1973, probablemente debido a los controles epidemiológicos efectuados en la zona, y que el porcentaje de positividad entre los mayores de 15 años se ha mantenido en el mismo nivel desde la última encuesta practicada en ese año de 1973

Fracciones de cerebro de raton que inhiben inespecificamente la hemaglutinacion de algunos togavirus. / Mouse brain fractions of mice inhibiting inespecifically the hemagglutination of some togairridae

Se estudiaron fracciones obtenidas de cerebro de raton albino suizo de 10 dias de edad desde el punto de vista fisico, quimico y biologico. Se confirmo su constitucion predominantemente proteica; cuando la alfa-quimotripsina actua sobre ellas por un lapso de 120 segundos, se liberan aminoacidos y/o pequenos peptidos, perdiendose la propiedad biologica de inhibir la hemaglutinacion del virus de la encefalitis equina del este. Se demostro que la fraccion biologicamente activa contiene glico y lipoproteinas. El tratamiento con SDA destruyo las lipotroteinas y expuso grupos glicoproteicos. Las fracciones calentadas evidenciaron mas grupos neuraminicos, que reaccionan con la o-fenantrolina, absorbiendo mas al UV. Se comprobo la presencia de lipidos neutros que no fueron identificados. El punto isoionico dio un valor de 4,16 +/- 0,17, indicativo de la presencia de grupos acidos