Comparative efficacy of different Carbopol concentrations as a stabilizer of live attenuated sheep pox virus vaccine against lumpy skin disease

In Egypt, the lyophilized live attenuated sheep pox virus vaccine has been used for the vaccination of cattle against lumpy skin disease virus to control its economic impact on livestock industry. In this endeavor, we validate the efficacy of Carbopol® as a stabilizer and adjuvant to enhance immunogenicity of such a heterologous sheep pox virus vaccine against lumpy skin disease. Lyophilization of sheep pox virus vaccine stabilized with Carbopol® produced better physical and antigenic properties than freeze-drying with lactalbumin/sucrose stabilizer; this was manifested by superior disc uniformity, thermo-stability at 37oC, and less reduction in virus titer. Immunization of calves' groups with variable sheep pox vaccine doses containing different Carbopol® concentrations revealed that 103.5 TCID50 of sheep pox virus vaccine enclosing 0.5 percent Carbopol® is the field dose of choice. Moreover, it induced protective serum neutralizing index of 2.5 and a ELISA S/P ratio of 36, by the 4th week post vaccination. Besides, the inclusion of 0.5 percent Carbopol® in formulation of the sheep pox virus vaccine was safe in bovines and enhanced cellular immune response to lumpy skin disease virus, as evidenced by increased T cell proliferation. Hence, it is recommended to use Carbopol® as 0.5 percent in preparation of live attenuated sheep pox virus vaccine to confer better protection against lumpy skin disease virus infection(AU)

En Egipto, la vacuna atenuada liofilizada contra el virus de la viruela ovina ha sido utilizado para la vacunación del ganado, contra el virus de la dermatosis nodular contagiosa, para controlar su impacto económico en la industria ganadera. En este trabajo, validamos la eficacia del Carbopol®, como estabilizador y adyuvante, para mejorar la inmunogenicidad de dicha vacuna heteróloga contra la dermatosis nodular contagiosa. La liofilización de la vacuna contra el virus de la viruela ovina estabilizada con Carbopol®, resultó en mejores propiedades físicas y antigénicas que la liofilización con el estabilizador de lactoalbúmina/sacarosa; lo anterior se manifestó en la uniformidad superior del disco, la termoestabilidad a 37°C y la menor reducción del título del virus. La inmunización de grupos de terneros con dosis variables de vacuna contra el virus de la viruela ovina, que contenían diferentes concentraciones de Carbopol®, reveló que la dosis de campo de elección fue 103,5 TCID50 de la vacuna contra el virus de la viruela ovina conteniendo 0,5 por ciento de Carbopol®, la que indujo un índice de neutralización sérica protectora de 2,5 y una relación S/P de ELISA de 36 a la cuarta semana después de la vacunación. Además, la inclusión de Carbopol® al 0,5 por ciento en la formulación de la vacuna contra el virus de la viruela ovina fue segura en los bovinos y potenció la respuesta inmunitaria celular contra el virus de la dermatosis nodular contagiosa, como lo demuestra el aumento de la proliferación de células T. Por lo tanto, se recomienda el uso de Carbopol® al 0,5 por ciento en la preparación de la vacuna viva atenuada contra el virus de la viruela ovina para conferir una mejor protección contra la infección por el virus de la dermatosis nodular contagiosa(AU)

Evaluation of pathogen P21 protein as a potential modulator of the protective immunity induced by Trypanosoma cruzi attenuated parasites

BACKGROUND TcP21 is a ubiquitous secreted protein of Trypanosoma cruzi and its recombinant form (rP21) promotes parasite cell invasion and acts as a phagocytosis inducer by activating actin polymerisation in the host cell. OBJECTIVE Our goal was to evaluate if the additional supplementation of rP21 during a prime/boost/challenge scheme with T. cruzi TCC attenuated parasites could modify the well-known protective behavior conferred by these parasites. METHODS The humoral immune response was evaluated through the assessment of total anti-T. cruzi antibodies as well as IgG subtypes. IFN-γ, TNF-α and IL-10 were measured in supernatants of splenic cells stimulated with total parasite homogenate or rP21. FINDINGS Our results demonstrated that, when comparing TCC+rP21 vs. TCC vaccinated animals, the levels of IFN-γ were significantly higher in the former group, while the levels of IL-10 and TNF-α were significantly lower. Further, the measurement of parasite load after lethal challenge showed an exacerbated infection and parasite load in heart and skeletal muscle after pre-treatment with rP21, suggesting the important role of this protein during parasite natural invasion process. MAIN CONCLUSION Our results demonstrated that rP21 may have adjuvant capacity able to modify the cytokine immune profile elicited by attenuated parasites.

Análisis de la evidencia sobre eficacia y seguridad de la vacuna de dengue CYD-TDV y su potencial registro e implementación en el Programa de Vacunación Universal de México / Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico's Universal Vaccination Program

El dengue es un importante problema de salud pública global, que afecta a América Latina y México. Las medidas de prevención y control centradas en vigilancia epidemiológica y control de vectores han resultado parcialmente efectivas y costosas, por lo que el desarrollo de una vacuna contra el dengue ha creado grandes expectativas entre las autoridades sanitarias y las comunidades científicas en el mundo. Sólo la vacuna CYD-TDV, producida por Sanofi-Pasteur, ha sido evaluada en ensayos clínicos controlados fase 3. No obstante a pesar de la importante contribución que esto significa para el desarrollo de una vacuna contra el dengue, los tres estudios clínicos fase 3 de CYD-TDV y el metaanálisis de seguimiento a largo plazo derivado de los mismos proporcionan evidencia de que esta vacuna tiene una eficacia parcial para proteger contra dengue virológicamente confirmado. Al respecto, surgen cuatro consideraciones: a) eficacia adecuada contra infecciones por virus de dengue (DENV) 3 y 4, menor eficacia contra infecciones por DENV 1 y prácticamente nula protección contra infecciones por DENV 2; b) disminución de la eficacia en individuos seronegativos a dengue al inicio de la vacunación; c) 83 y 90% de protección contra hospitalizaciones y formas de dengue grave, respectivamente, a 25 meses de seguimiento, y d) incremento de hospitalización por dengue, en el grupo de vacunados, en niños menores de nueve años de edad al momento de la vacunación, detectado a partir del tercer año de seguimiento. El beneficio de la vacuna CYD-TDV se puede resumir en la protección contra infecciones por DENV 3 y 4, así como en la protección de hospitalizaciones y casos graves en individuos mayores de nueve años y en quienes han tenido infección previa por dengue, pues funciona principalmente como una vacuna de refuerzo. En esta revisión se identificaron elementos sobre eficacia y seguridad de esta vacuna que deben ser tomados en cuenta ante el potencial registro e inclusión en el programa de vacunación en la población mexicana. La evidencia científica disponible sobre la vacuna CYD-TDV demuestra méritos, pero también da lugar a preguntas relevantes que deberían ser contestadas para evaluar apropiadamente el perfil de seguridad del producto, así como las poblaciones blanco de potencial beneficio. Al respecto, consideramos que sería informativo completar el seguimiento indicado de seis años después de iniciar la vacunación, de acuerdo con el protocolo propuesto en los propios estudios del fabricante como una recomendación de la Organización Mundial de la Salud. Al igual que con cualquier nueva vacuna, el potencial registro e implementación de uso de CYD-TDV en el programa nacional de vacunación de México requiere una definición clara de cuál es el balance entre los beneficios y riesgos esperados. En particular, ante una vacuna con eficacia variable y algunas señales de riesgo, en caso de aprobar el registro, se deben desarrollar protocolos de manejo de riesgos detallados que permitan identificar de manera oportuna cualquier evento de salud asociado con la vacunación.

Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that should be answered to properly assess the safety profile of the product and the target populations of potential benefit. In this regard we consider it would be informative to complete the 6-year follow-up after starting vaccination, according to the company's own study protocol recommended by the World Health Organization. As with any new vaccine, the potential licensing and implementation of the CYD-TDV as part of Mexico's vaccination program, requires a clear definition of the balance between the expected benefits and risks. Particularly with a vaccine with variable efficacy and some signs of risk, in the probable case of licensing, the post-licensed period must involve the development of detailed protocols to immediately identify risks or any health event associated with vaccination.

Assessment of the pathogenicity of cell-culture-adapted Newcastle disease virus strain Komarov

Newcastle disease vaccines hitherto in vogue are produced from embryonated chicken eggs. Egg-adapted mesogenic vaccines possess several drawbacks such as paralysis and mortality in 2-week-old chicks and reduced egg production in the egg-laying flock. Owing to these possible drawbacks, we attempted to reduce the vaccine virulence for safe vaccination by adapting the virus in a chicken embryo fibroblast cell culture (CEFCC) system. Eighteen passages were carried out by CEFCC, and the pathogenicity was assessed on the basis of the mean death time, intracerebral pathogenicity index, and intravenous pathogenicity index, at equal passage intervals. Although the reduction in virulence demonstrated with increasing passage levels in CEFCC was encouraging, 20% of the 2-week-old birds showed paralytic symptoms with the virus vaccine from the 18^th(final) passage. Thus, a tissue-culture-adapted vaccine would demand a few more passages by CEFCC in order to achieve a complete reduction in virulence for use as a safe and effective vaccine, especially among younger chicks. Moreover, it can be safely administered even to unprimed 8-week-old birds.

Rotavirus vaccine trial in Jamaica / Prueba de la vacuna contra el rotavirus en Jamaica

Worldwide, rotaviruses have been a significant cause of dehydrating gastroenteritis. This contributed to increased infant morbidity and mortality in Jamaica. We enrolled 1804 Jamaican infants in the international randomized, placebo-controlled, pentavalent (G1, G2, G3, G4 and P1) rotavirus vaccine trial. This pentavalent vaccine was found to significantly reduce rotavirus gastroenteritis attributable emergency room visits and hospitalizations, without increasing the rates of intussusception, or other serious adverse events in Jamaican infants. It is recommended that the rotavirus vaccine be included in Jamaica's National Immunization Programme in accordance with recommendations from the World Health Organization.

A nivel mundial, los rotavirus han sido una de las causas fundamentales de la gastroenteritis deshidratante, contribuyendo por ende a la morbilidad y mortalidad infantil en Jamaica. En este estudio se enrolaron 1804 infantes jamaicanos en una prueba internacional de vacuna contra el rotavirus pentavalente (G1, G2, G3, G4 y P1), randomizada, con control placebo. Se halló que la vacuna pentavalente reducía de manera significativa las hospitalizaciones y visitas a la sala de emergencia por causas atribuibles al rotavirus, sin aumentar las tasas de invaginación, u otros serios eventos adversos en los niños jamaicanos. Se recomienda que la vacuna del rotavirus sea incluida en el Programa de Inmunización Nacional de Jamaica, de conformidad con las recomendaciones de la Organización de Mundial de la Salud.

Typhoid fever & vaccine development: a partially answered question.

Typhoid fever is a systemic disease caused by the human specific Gram-negative pathogen Salmonella enterica serovar Typhi (S. Typhi). The extra-intestinal infections caused by Salmonella are very fatal. The incidence of typhoid fever remains very high in impoverished areas and the emergence of multidrug resistance has made the situation worse. To combat and to reduce the morbidity and mortality caused by typhoid fever, many preventive measures and strategies have been employed, the most important being vaccination. In recent years, many Salmonella vaccines have been developed including live attenuated as well as DNA vaccines and their clinical trials have shown encouraging results. But with the increasing antibiotic resistance, the development of potent vaccine candidate for typhoid fever is a need of the hour. This review discusses the latest trends in the typhoid vaccine development and the clinical trials which are underway.

Vacuna anti-influenza en niños: estado del arte / Flu vaccine in children: state of the art

La influenza es una enfermedad respiratoria aguda con elevada tasa de morbilidad y mortalidad anual. Todos los niños, tanto sanos como aquellos de alto riesgo son susceptibles a la infección. La vacuna anti-influenza es eficaz en prevenir síntomas asociados a influenza, infección demostrada por laboratorio, hospitalizaciones y muertes y ha demostrado ser una medida costo-efectiva. No se han observado claras diferencias entre las vacunas inactivadas y las nuevas vacunas elaboradas con virus vivo atenuado. Por la elevada tasa de hospitalización que los afecta, algunos países han resuelto recomendar la vacunación universal de los lactantes sanos entre 6 y 24 meses de edad. Considerando que esta medida de salud pública también ha sido incorporada en Chile, serían necesarios estudios locales que evalúen su real impacto en nuestro medio.

Ensayo preclinico de la vacuna candid #1 producida en Argentina contra la fiebre hemorragica Argentina / Preclinical assay of candid #1 vaccine against argentine hemorrhagic fever made in Argentina

Se comparó en cobayos la seguridad, inmunogenicidad y eficácia protectora de um lote de vacuna Candid #1 (C#1) fabricada en Estados Unidos de América (EE.UU.) y distintos lotes de la misma vacuna fabricados en Argentina (Arg.). El lote TSI 5-1-92 (EE.UU) y los lotes Exp N3, 7A y 8A (Arg) fueron inoculados (0.5ml, IM) en cobayos de 250400g. Para cada ensayo diez animales recibieron solución fisiológica y sirvieron como control. Todos fueron desafiados con la cepa patógena P23790 de vírus Junin. Se registro: a) temperatura rectal, b) peso corporal , c) presencia de anticuerpos neutralizantes (AcNT) pré y post-vacunación, d) respuesta al desafio . Todos los animales vacunados desarrollaron AcNT anti vírus Junin (rango= 4081920 y sobrevivieron al desafio. En cada grupo control 810 animales murieron (dia 23.3+_ 5.4 post- desaportada y los diferentes lotes de C#1 producidos en Argentina.

Antibody response in cattle after vaccination with inactivated and attenuated rabies vaccines

Despite the absence of current official reports showing the number of cattle infected by rabies, it is estimated that nearly 30,000 bovines are lost each year in Brazil. In order to minimize the important economic losses, control of the disease is achieved by eliminating bat colonies and by herd vaccination. In this study, we compare the antibody response in cattle elicited by vaccination with an attenuated ERA vaccine (AEvac) and an inactivated-adjuvanted PV (IPVvac) vaccine. The antibody titers were appraised by cell-culture neutralization test and ELISA, and the percentage of seropositivity was ascertained for a period of 180 days. IPVvac elicited complete seropositivity rates from day 30 to day 150, and even on day 180, 87 per cent of the sera showed virus-neutralizing antibody titers (VNA) higher than 0.5IU/ml. There were no significant differences between the VNA titers and seropositivity rates obtained with IPVvac in the two methods tested. AEvac, however, elicited significantly lower titers than those observed in the group receiving inactivated vaccine. In addition, the profiles of antirabies IgG antibodies, evaluated by ELISA, and VNA, appraised by cell-culture neutralization test, were slightly different, when both vaccines were compared.