Evaluación de emergencia de una vacuna existente contra el virus de la fiebre aftosa tipo SAT2, aislado recientemente en Egipto en el 2018 / Emergency evaluation for existing vaccine against recently isolated Foot and mouth disease virus type SAT2 in Egypt 2018

El virus de la fiebre aftosa es un patógeno altamente infeccioso y contagioso. Recientemente, el topotipo VII, linaje Lib-12 del serotipo SAT2 se describió en brotes en Egipto durante 2018. La vacunación es una forma eficaz de controlar y combatir los brotes del virus de la fiebre aftosa, especialmente en áreas endémicas como Egipto. El presente estudio tuvo como objetivo evaluar la eficacia de la vacuna contra la fiebre aftosa que se produce actualmente, frente a la cepa de campo recientemente aislada del virus de la fiebre aftosa SAT2 topotipo VII, linaje Lib-12 (SAT2 Libia), mediante la aplicación de estudios in vitro e in vivo. Se inocularon en terneros, dos lotes de la vacuna actual contra el virus de la fiebre aftosa. A los 28 días posteriores a la vacunación, se recolectaron muestras de suero y se analizaron contra el virus de la fiebre aftosa SAT2 Libia adaptado a cultivo de tejidos y SAT2/EGY/2/2012 utilizando una prueba de neutralización viral para determinar la relación serológica (valor r1). El ensayo de reto en terneros vacunados se llevó a cabo empleando una cepa virulenta de la fiebre aftosa SAT2 Libia. Se encontró que los títulos de anticuerpos neutralizantes inducidos por los dos lotes de vacuna (1 y 2) y los de animales no vacunados, fueron 0,48, 0,39 y 0,15 log10 DICT50/mL, respectivamente, mientras que la prueba reveló valores de protección de 20 por ciento, 0 por ciento y 0 por ciento, respectivamente. Además, los valores de r1 fueron 0,195 y 0,186 para los lotes de vacuna (1 y 2), respectivamente. Se llegó a la conclusión de que los lotes de vacunas locales comerciales inactivadas disponibles actualmente (SAT2 SAT2/EGY/2/2012) no protegen a los terneros contra el virus circulante de la fiebre aftosa SAT2 topotipo VII, linaje Lib-12 que se aisló recientemente, por lo que es recomendable actualizar las vacunas existentes con la cepa aislada actualmente(AU)

Foot and mouth disease virus is a highly infectious and contagious pathogen. Recently the topotype VII, Lib‐12 lineage of serotype SAT2 was reported through outbreaks in Egypt during 2018. Vaccination is an effective way to control and combat the foot and mouth disease virus outbreaks especially in endemic areas like Egypt. The present study was aimed to evaluate the efficacy of the current produced foot and mouth disease vaccine, against the recently isolated field strain foot and mouth disease virus SAT2 topotype VII, Lib-12 lineage (SAT2 Libya), by applying in vitro and in vivo studies. Two batches of the current foot and mouth disease virus vaccine were inoculated in calves. At the 28th day post-vaccination serum samples were collected and tested against tissue culture adapted foot and mouth disease virus SAT2 Libya and SAT2/EGY/2/2012 using virus neutralization test to determine serological relationship (r1-value). The challenge test for vaccinated calves was carried out against the virulent foot and mouth disease virus SAT2 Libya. It was found that neutralizing antibody titers induced by the two vaccine batches (1 and 2) and those in unvaccinated animals were 0.48, 0.39 and 0.15 log10 TCID50/mL, respectively, while the challenge revealed protection values of 20 percent, 0 percent and 0 percent, respectively. Furthermore, the r1 values were 0.195 and 0.186 for vaccine batches (1 and 2), respectively. It was concluded that the available local commercial inactivated foot and mouth disease virus vaccine batches (SAT2 SAT2/EGY/2/2012) are unable to protect calves against the current circulating foot and mouth disease virus field isolate SAT2 topotype VII, Lib-12 lineage, thus it is highly recommended to update the existing vaccines with the present isolated strain(AU)

Remarks on the possibility of introducing the fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule

Abstract Given that the last notified case of poliomyelitis due to wild poliovirus type 2 was in 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of a bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported a reduction of the global supply of IPV. In response to the potential shortage of IPV, at a meeting held on March 10 2017, the SAGE and Technical Advisory Group (TAG) of the Pan American Health Organization (PAHO) urged the countries in the Latin American region to replace the routine administration of the full doses of inactivated polio vaccine (IPV-C) in the immunization schedule (administered by intramuscular route), administering a fraction of the full dose in two intradermal shots (IPV-f). The possibility of this strategy was analyzed by opinion leaders convened by the Paraguayan Society of Pediatrics with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). This document presents the results of the discussion.

Métodos alternativos como parte de las nuevas tendencias en el control de calidad de vacunas / Alternative methods as part of the new trends in vaccine quality control

El control de calidad de las vacunas resulta fundamental para las actividades de producción, liberación lote a lote y comercialización de las vacunas. Sin embargo, en la actualidad este es un proceso que por su concepción es lento y costoso debido a que se apoya en la realización de extensas pruebas en animales para demostrar la potencia y seguridad de estos productos biológicos. El desarrollo de métodos alternativos inspirados en el principio de las 3Rs (Reducción, Refinamiento y Reemplazo) constituye una tendencia que debe impactar de manera muy significativa en la reducción de los tiempos de liberación y el costo del proceso de control de calidad de vacunas en los próximos años. En particular la sustitución de las pruebas de potencia y toxicidad in vivo por procedimientos alternativos más relevantes, rápidos, exactos, reproducibles, robustos y baratos, que incluyen la serología, la cuantificación directa de antígeno, los ensayos en cultivos celulares y el enfoque a consistencia, por solo mencionar algunos; implica un cambio de paradigma, con indiscutibles repercusiones éticas, logísticas, económicas y científico-técnicas, para el aseguramiento de los parámetros de calidad de los inmunobiológicos con el mejor balance costo-beneficio: las vacunas. Los fundamentos técnicos de estos métodos alternativos, sus ventajas y nivel de implementación a nivel internacional, así como sus principales limitaciones, son abordados en este trabajo(AU)

Vaccine quality control is crucial for the manufacturing, lot release and commercialization activities worldwide. However, the current process is by-design too slow and expensive because is based on large animal assays for assuring the potency and safety of these important biological products. The development of 3Rs alternative methods (Reduction, Refinement and Replacement) is a trend able to significantly reduce the releasing times and costs of the vaccine quality control processes in the next few years. Particularly, the replacement of the animals-based potency and toxicity assays by alternative procedures more relevant, fast, accurate, reproducible and cheap, including serology, direct antigen quantification, cell culture tests and the Consistency Approach, for just mentioning some of them, implies a paradigm shift, with undisputable ethical, logistical, economic, scientific and technical repercussions for ensuring the vaccine quality parameters. Theoretical basements, advantages and implementation levels of the alternatives methods as well as their main limitations are presented in this paper(AU)

The 2nd Meeting of National Control Laboratories for Vaccines and Biologicals in the Western Pacific

The Second Meeting of the National Control Laboratories for Vaccines and Biologicals in the Western Pacific, was jointly organized by the National Institute of Food and Drug Safety Evaluation of the Ministry of Food and Drug Safety in the Republic of Korea, and by the World Health Organization Regional Office for the Western Pacific. In the National Lot Release Systems session countries including Canada, China, Japan, Malaysia, Vietnam, and the Republic of Korea, all shared information on their current Lot Release Systems, including current practices and developments in risk-based official lot release of vaccines. In the session on Quality Control of Blood Products, experts from the National Institute for Biological Standards and Control shared quality control and research results for; blood coagulation factor VIII products, and the measurement of procoagulant activity in immunoglobulin products. Representatives from Japan proposed a regional collaborative study to test aggregated immunoglobulin free from complement activity. A cell-based Japanese encephalitis vaccine potency assay was proposed by representatives from Korea and they also called for voluntary participation of other National Control Laboratories in a collaborative study, on the first Korean Gloydius anti-venom standard. Participants agreed in general to continue communicating, and coordinate presentation of the study results.

Development of a New Approach to Determine the Potency of Bacille Calmette–Guérin Vaccines Using Flow Cytometry

OBJECTIVES: To circumvent the limitations of the current golden standard method, colony-forming unit (CFU) assay, for viability of Bacille Calmette–Guérin (BCG) vaccines, we developed a new method to rapidly and accurately determine the potency of BCG vaccines. METHODS: Based on flow cytometry (FACS) and fluorescein diacetate (FDA) as the most appropriate fluorescent staining reagent, 17 lots of BCG vaccines for percutaneous administration and 5 lots of BCG vaccines for intradermal administration were analyzed in this study. The percentage of viable cells measured by flow cytometry along with the total number of organisms in BCG vaccines, as determined on a cell counter, was used to quantify the number of viable cells. RESULTS: Pearson correlation coefficients of FACS and CFU assays for percutaneous and intradermal BCG vaccines were 0.6962 and 0.7428, respectively, indicating a high correlation. The coefficient of variation value of the FACS assay was less than 7%, which was 11 times lower than that of the CFU assay. CONCLUSION: This study contributes to the evaluation of new potency test method for FACS-based determination of viable cells in BCG vaccines. Accordingly, quality control of BCG vaccines can be significantly improved.

Influence of vaccine potency and booster administration of foot-and-mouth disease vaccines on the antibody response in calves with maternal antibodies

Foot-and-mouth disease is one of the most important viral diseases of cloven-hoofed animals. Mass vaccination is an effective method to control the disease and is frequently utilized in endemic regions. Sufficient protection of young animals is important in mass vaccination campaigns. Maternal antibodies negatively affect the success of vaccination. Hence, determination of the optimal vaccination age is crucial for the uninterrupted protection of young animals. This study was performed to identify the effect of vaccine potency and booster administration on serum neutralizing antibody titers of calves with different levels of maternal antibodies. Calves (n = 111) on a state farm were used in this study. Oil adjuvant foot-and-mouth disease vaccines with 3 PD₅₀ and 6 PD₅₀ potencies were used with or without booster administration. Serum samples were collected each month up to day 120 postvaccination. Virus neutralization tests were used to measure the serum neutralizing antibody titers and estimate the protection period by using pre-determined cut-off values for protection. The results revealed that a vaccination with a 6 PD₅₀ potency vaccine, preferably followed by a booster dose, should be used to overcome maternal immunity for incessant protection.

Correlations in the results of virus neutralization test, hemagglutination inhibition test, and enzyme-linked immunosorbent assay to determine infectious bronchitis virus vaccine potency

The virus neutralization (VN) test was used to determine potency of the infectious bronchitis (IB) vaccine. The results of VN, hemagglutination inhibition (HI), and enzyme-linked immunosorbent assay (ELISA) were compared with those of the IBV M41. The r² values between VN and HI titers and the ELISA antibody titer were 0.8782 and 0.0336, respectively, indicating a high correlation between VN and HI, but not VN and ELISA. The Cohen's kappa coefficient between the VN titer of 2 log₁₀ and HI titer of 5 log₂ was 0.909. Our results showed that VN could be replaced with HI for testing the potency of IBV M41.

Varicella breakthrough infection and vaccine effectiveness with 1-dose varicella / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the breakthrough varicella infection rate and varicella vaccine effectiveness (VE) among children who received 1-dose varicella vaccine.</p><p><b>METHODS</b>A total of 57 180 subjects for the consecutive 4-year birth cohorts were selected from the local children born between 2007 and 2010 in Yinzhou District, Ninghai County and Yuyao City. And they were followed up for varicella from 2008 to 2013. The recipients of the vaccinations were identified through Ningbo Immunization Information System and data on breakthrough infections among the recipients were collected by using China Information System for Disease Control and Prevention. The breakthrough varicella rate and the VE were calculated and the trends of them were described from 2008 to 2013 among 4-year birth cohorts. The cumulative incidence of varicella was compared between vaccinated and unvaccinated children among the consecutive 4-year birth cohorts.</p><p><b>RESULTS</b>The rate of varicella vaccine coverage, vaccine cumulative incidence among the cohorts was 96.74% (55 317/57 180) and 0.56% (321/57 180). The breakthrough varicella infection for 4-year birth cohorts was 0.44% (244/55 317), and for each birth cohort was 0.95% (142/14 928), 0.44% (61/13 855), 0.22% (29/13 433) and 0.09% (12/13 101), respectively. It was on the rise from 2008 to 2013 and the 2007 birth cohort of it increased fastest from 0.04% (6/14 928) in 2007 to 0.32% (48/14 834) in 2013. The vaccine cumulative incidence of these who vaccinated 1-dose varicella (the breakthrough varicella infection) was lower than these who were unvaccinated (the incidence: 6.25% (37/592), 3.52% (15/426), 3.69% (17/461) and 2.08% (8/384)) by each birth cohort (χ²= 130.27, P < 0.001 for 2007 birth cohort; χ²= 74.11, P < 0.001 for 2008 birth cohort; χ²= 162.80, P < 0.001 for 2009 birth cohort; χ²= 100.01, P < 0.001 for 2010 birth cohort). The vaccine effectiveness for 4-year birth cohorts was 89.33% (95% CI: 86.7%-92.1%) and for each birth corhort was 84.78% (95% CI: 77.94%-89.50%), 86.82% (95% CI: 77.82%-92.95%), 93.99% (95% CI: 89.27%-96.81%) and 95.60% (95% CI: 89.18%-98.21%), respectively. The effectiveness of each birth cohort declinedgradually from 2008 to 2013 and the 2009 birth cohort of it decreased fastest from 98.86% in 2010 to 66.83% in 2013.</p><p><b>CONCLUSIONS</b>The 1-dose varicella vaccine effectiveness was good, but breakthrough varicella infection rate was on the rise with time and the VE declined gradually from 2008 to 2013.</p>

Comparative studies of the potency of foot and mouth disease virus trivalent vaccine with different concentration of the antigenic content [146S]

Estimation of antigenic content [146S] of FMDV serotypes [A, O, SAT2] by sucrose density gradient [SDG] ultracentrifugation by determining the absorbance at 254 nm using ISCO520C density gradient system to produce a highly potent trivalent virus vaccine. The antigenic mass 146S [microg/ml] of serotype [O Pan Asia2, A Iran O5 and SAT2/EGY/2012] were 6.5, 6.2 and 5.9, respectively. The vaccine was injected into three groups of calves [2individuals/each group] subcutaneously in lateral part of the neck for a dose 3 ml [6.2 microg/serotype/ml], a dose 1.5 ml [4.1 microg/serotype/ml] and a dose 1 ml [2 micro/ml], the sera samples were collected at 7[th] day post vaccination [dpv], 14[th] dpv, 21[th] dpv, 28[th] dpv and every 2 wks till 40 weeks to evaluate the immune response along that period. The antibody titers/40wpv for a 3 ml dose [6.2 microg/ml] of serotypes [O Pan Asia-2, A Iran O5 and SAT-2/EGY/2012] were 2.08, 2 and 1.94, respectively [over the protective titer, PT=1.5 in SNT for cattle], a dose [4.1 microg/ml] of the three serotypes were 1.56, 1.62 and 1.63 [over PT], respectively, but for [2 microg/ml] dose of the three serotypes, the antibodies titer were 1.25, 1.19 and 1.2 [below PT], that show the antibodies titer depend on the concentration of the antigenic mass [146S] and with increase of the 146S concentration increase of the potency of the vaccine. The potency testing of the study depend upon the correlation between 146S and the neutralizing antibody titers were measured by SNT which are the perfect alternative of other potency tests which employ the challenge of the cattle with virulent virus. The immune response of the highly potent vaccine [4.1 microg/serotype/ml and 6.2 microg/serotype/ml] started early after 1[st] wpv and the protective titer remain for more than 38 wpv [especially in 6.2 microg/ml injected calves] and that confer the potency of the vaccine of that dose

Recent Advances of Vaccine Adjuvants for Infectious Diseases

Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.

Heat effect stability of inactivated enterovirus 71 vaccine / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of temperature on the stability of intermediate and final products of inactivated enterovirus 71 vaccine, which was prepared in human diploid cells.</p><p><b>METHODS</b>The different batches of harvest viral cultures, the vaccine stock solutions and the final productions of inactivated enterovirus 71 vaccine were stored at different temperatures. The samples of viral culture stored at -20°C or 4°C were harvested at 0, 6, 12 and 24 months later. The samples of vaccine stock solutions stored at -20°C were harvested at 0, 6, 12 and 24 months later, and that stored at 4°C were harvested at 0, 1, 3, 6 and 12 months later. The samples of finial products were harvested at different time points (0, 6, 12 and 24 months for storing at 4°C; 0, 7, 14, 28, 42 and 60 d for storing at 25°C; 0, 3, 7, 14 and 21 d for storing at 37°C). The viral titer, antigen content, antigen purity, endotoxin content, effectiveness, pH and appearance of samples were determined, respectively. A total of 1 800 BLAB/c mice were immunized by vaccine and 150 control mice were injected by diluents without antigen via intraperitoneal. The tail vein blood (500 µl per mouse) from 1 950 mice were harvested after 4 weeks post injected. The neutralization antibody titers of the serum were tested to calculate the half effective dose (ED50) of final products. All results were analyzed using analysis of variance to compare the differences of the above indexes.</p><p><b>RESULTS</b>The viral titers of harvest viral culture of inactivated EV71 vaccine were (6.67 ± 0.13), (6.56 ± 0.09), (6.52 ± 0.04), (6.39 ± 0.16) lgCCID50/ml (CCID50, the half cell culture infective dose) after 0, 6, 12 and 24 months storage at -20°C; and (6.67 ± 0.13), (6.41 ± 0.13), (6.19 ± 0.18), (5.97 ± 0.09) lgCCID50/ml at 4°C. The viral titers reduced with time (F = 9.81 or 44.16, P < 0.05). The antigen contents of the vaccine stock solution were maintained at (3 626.67 ± 1 382.56) EU/ml within 3 months at 4°C, but were (2 080.00 ± 876.36), (951.17 ± 346.35) EU/ml at 6 and 12 months, respectively. The ED50 of the final production were (31.00 ± 2.71), (32.93 ± 3.22), (39.37 ± 3.44) and (46.04 ± 3.25) EU/ml after 0, 6, 12 and 24 months storage at 4 °C, but were (31.00 ± 2.71), (32.23 ± 2.66), (34.70 ± 1.77), (40.04 ± 2.10), (47.78 ± 1.93) and (56.97 ± 0.50) EU/ml at 0, 7, 14, 28, 42 and 60 days at 25°C, and were (31.00 ± 0.00), (36.20 ± 0.00), (41.87 ± 0.50), (53.25 ± 0.50) and (64.84 ± 0.58) EU/ml at 0, 3, 7, 14 and 21 days at 37°C, respectively. The ED50 had increased with the time by and had significantly differences compared with the beginning level (F = 28.49, 215.15 or 156.12, P < 0.05).</p><p><b>CONCLUSION</b>There is a good stability of the intermediate and final productions of inactivated enterovirus 71 (EV71) vaccines, within 24 months at -20°C or 6 months at 4°C storage for viral culture, 24 months at -20°C or 3 months at 4°C storage for stock solution and 24 months at 4°C or 28 d at 25°C or 7 d at 37°C storage for finial vaccine.</p>

Controle da eficácia de bacterinas antileptospirose: relação entre os resultados dos testes de inibição de crescimento de leptospiras in vitro com os do desafio in vivo em hamsters / Efficacy of anti-leptospirosis bacterines: relation between the results of the in vitro growth inhibition test and the potency test, in vivo, with challenge in hamsters

Foi efetuada a comparação em hamsters da proteção conferida e dos níveis de anticorpos induzidos por duas bacterinas comerciais antileptospirose. Os ensaios empregados foram o teste oficial de potência com desafio (TP), o ensaio proposto, teste de inibição de crescimento de leptospiras in vitro (ICLIV) e a soroaglutinação microscópica (SAM). O protocolo de imunização foi representado por duas aplicações individuais de 0,25 mL das bacterinas, puras ou de suas diluições geométricas de razão dois variando de 200 a 51.200 para a bacterina A e de 200 a 3.200 para a bacterina B, por via subcutânea com o intervalo de 15 dias. Decorridos 15 dias da segunda aplicação de vacina, um grupo de animais foi desafiado com 0,2 mL de cultivos de leptospiras, por indivíduo, respectivamente dos sorovares Canicola (bacterinas A e B) ou Kennewicki (bacterina A). Os números de doses infectantes empregados nos desafios foram de 100 e 631 respectivamente, para os sorovares Canicola e Kennewicki. Decorridos 21 dias do desafio, os grupos de animais utilizados nos testes de ICLIV e SAM foram sangrados e os seus soros foram reunidos em pools (n = 5). No TP, adotando-se os critérios internacionais, as bacterinas foram aprovadas. A comparação do desempenho das bacterinas para os sorovares adotados, segundo sua concentração, por meio das proporções de animais sobreviventes ao TP e a média dos títulos de anticorpos identificados no teste de ICLIV, indicou que um título igual ou superior a 0,77 log corresponde ao nível de aprovação da bacterina no TP.

It was performed a comparison between the protection afforded in hamsters and the antibody levels induced by two commercial vaccines against leptospirosis. The assays used were the official challenge test (TP), the in vitro leptospires growth inhibition test (ICLIV) and microscopic agglutination test (MAT). The immunization protocol consisted of two single applications, 15 days from each other, of 0.25 mL of the bacterins, pure or its two-fold serial dilutions: 200 to 51,200 for bacterin A and 200 to 3.200 bacterin B, both of them administered subcutaneously. A group of animals was challenged, after 15 days from the second vaccine application, with 0.2 mL/animal of live leptospire cultures, with Canicola (bacterin A and B) or Kennewicki (bacterin A) serovars. The numbers of infective doses employed in the challenges were 100 and 631 for Canicola and Kennewicki serovars, respectively. After 15 days from the second vaccine dose the groups of animals used in ICLIV and SAM tests were bled and their sera were collected in pools (n = 5). In TP, adopting the criteria established by the Code Federal Regulation, both bacterins were approved. The comparison of the performance of the tested bacterins with the adopted serovars, according to its concentration, by the proportions of surviving animals to the challenge assay and the average of the neutralizing antibodies titers, established a neutralizing antibodies titer equal or higher than 0.77 log corresponding with the bacterin level of approval in the potency assay.

Measles in previously vaccinated children

No abstract available.