Vacinas Covid-19: eficácia e segurança / Covid-19 vaccines: efficacy and safety

A síntese trata da eficácia e segurança das vacinas contra Covid-19 em desenvolvimento no mundo. Os estudos utilizados como base para o registro e liberação de vacinas para a imunização da população são divididos em três fases. Na fase I os ensaios clínicos têm como objetivo principal avaliar a segurança e a melhor forma de administração do produto testado, já na fase II os principais objetivos são avaliar qual será a melhor dose e o intervalo de tempo ideal entre as doses para garantir a eficácia da imunização, a fase III tem como objetivo avaliar se a vacina apresenta resposta imunológica protetora aos humanos que estão em contato com a doença em estudo. (INSTITUTO BUTANTAN, 2020).

The synthesis addresses the efficacy and safety of covid-19 vaccines in development worldwide. The studies used as a basis for the registration and release of vaccines for immunization of the population are divided into three phases. In phase I the clinical trials have as main objective to evaluate the safety and the best way of administration of the tested product, already in phase II the main objectives are to evaluate what will be the best dose and the ideal time interval between doses to ensure the effectiveness of immunization, phase III aims to evaluate whether the vaccine presents protective immune response to humans who are in contact with the disease under study. (BUTANTAN INSTITUTE, 2020)

About the necessity of including HoBi-like pestiviruses in bovine respiratory and reproductive viral vacines / Sobre a necessidade de incluir pestivírus HoBi-like em vacinas virais respiratórias e reprodutivas para bovinos

HoBi-like pestiviruses (HoBiPeV) constitute a novel group of bovine pestiviruses, genetically and antigenically related to bovine viral diarrhea virus 1 (BVDV-1) and BVDV-2. Recent data shows that HoBiPeV are endemic among Brazilian cattle, yet bovine reproductive/respiratory vaccines contain only BVDV-1 and BVDV-2 strains. The present study investigated the neutralizing antibody response against these pestiviruses induced by two commercial vaccines (VA = attenuated, VI = inactivated) and by three experimental, replicative, vaccine formulations (VAC1 = monovalent, BVDV-1; VAC2 = bivalent, BVDV-1 + BVDV-2; VAC3 = trivalent, BVDV-1 + BVDV-2 and HoBiPeV). Seronegative beef calves were immunized once (replicative vaccines) or twice (inactivated vaccine) and serum samples were tested by virus-neutralization (VN) 30 days after vaccination (dpv) (replicative vaccines) or 30 days after the second dose (VI). We considered a threshold VN titer of ≥60 indicative of protection against clinical disease. At 30 dpv, VA induced protective titers against BVDV-2 in 7/7 animals (GMT=289.8) and against BVDV-1 and HoBiPeV in 5/7 animals (GMTs=97.5 and 80, respectively). VI induced protective titers against BVDV-1 in 1/7 animal (GMT=16.4), 2/7 animals against BVDV-2 (GMT=53.8) and in none of the calves against HoBiPeV (GMT=12.2). When a pool of sera of each vaccine group was tested against individual Brazilian isolates, VA induced protective titers against 3/7 BVDV-1 isolates, to 9/10 (BVDV-2) and 1/8 (HoBiPeV); VI induced protective titers against 1/7 (BVDV-1), 1/10 (BVDV-2) and none (0/8) HoBiPeV isolates. The experimental vaccine VAC1 induced protective titers against BVDV-1 in 9/9 animals (GMT=320) but in no animal against BVDV-2 or HoBiPeV (GMT<10). VAC2 induced protective titers to BVDV-1 and BVDV-2 in 9/9 animals (GMTs=160 and 640, respectively), and against HoBiPeV in 7/9 animals (GMT=108.5). Finally, VAC3 induced protective titers in all animals against BVDV-1 (GMT=234.3), BVDV-2 (294.9) and HoBiPeV (201.1). Testing the pool of sera against pestivirus isolates, VAC1 induced titers ≥ 60 against 4/7 BVDV-1 but to none BVDV-2/HoBiPeV isolate; VAC2 induced protective titers against 4/7 BVDV-1; 10/10 BVDV-2 and 2/8 HoBiPeV; VAC3 induced protective titers against all BVDV-1, BVDV-2 and HoBiPeV isolates. These results indicate that vaccines composed by BVDV-1+BVDV-2, especially those containing inactivated virus, may not induce serological response against a variety of HoBiPeV isolates. Thus, the need of inclusion of HoBiPeV in vaccine formulations should be considered.(AU)

Os pestivírus HoBi-like (HoBiPeV) compõe um grupo novo de pestivírus de bovinos, genética e antigenicamente relacionados com os vírus da diarreia viral bovina 1 e 2 (BVDV-1, BVDV2). Dados recentes indicam que os HoBiPeV são endêmicos na população bovina do Brasil, mas as vacinas respiratórias e reprodutivas bovinas contêm apenas cepas de BVDV-1 e BVDV-2. O presente estudo investigou a atividade neutralizante contra estes pestivírus induzidas por duas vacinas comerciais (VA = atenuada, VI = inativada) e por três vacinas experimentais replicativas (VAC1 = monovalente, BVDV-1; VAC2 = bivalente, BVDV-1 + BVDV-2; VAC3 = trivalente, BVDV-1 + BVDV-2 e HoBiPeV). Bezerros soronegativos foram imunizados uma vez (vacinas replicativas) ou duas (vacina inativada) e amostras de soro foram testadas por vírus-neutralização (VN) 30 dias após a vacinação (dpv) (vacinas replicativas) ou 30 dias após a segunda dose (VI). Títulos neutralizantes ≥60 foram considerados indicativos de proteção contra doença clínica. Nesta data, a VA induziu títulos protetivos contra o BVDV-2 em 7/7 animais (GMT=289,8) e contra BVDV-1 e HoBiPeV em 5/7 animals (GMTs=97,5 e 80, respectivamente). VI induziu títulos protetores contra BVDV-1 em 1/7 animal (GMT=16,4), em 2/7 animais contra BVDV-2 (GMT=53,8) e em nenhum contra HoBiPeV (GMT=12,2). Quando um pool de soro de cada grupo vacinal foi testado frente a isolados Brasileiros, a VA induziu títulos protetores contra 3/7 isolados de BVDV-1, 9/10 (BVDV-2) e 1/8 (HoBiPeV); VI induziu títulos protetores em 1/7 contra BVDV-1, 1/10 (BVDV-2) e em nenhum (0/8) contra isolados de HoBiPeV. A VAC1 induziu títulos protetores contra BVDV-1 em 9/9 animais (GMT=320) mas em nenhum animal contra BVDV-2 ou HoBiPeV (GMT<10). VAC2 induziu títulos protetores contra BVDV-1e BVDV-2 em 9/9 animais (GMTs=160 e 640, respectivamente),e contra HoBiPeV em 7/9 animais (GMT=108,5). Finalmente, VAC3 induziu títulos protetores em todos os animais contra BVDV-1 (GMT=234,3), BVDV-2 (294,9) e HoBiPeV (201,1). No teste de pool de soro contra isolados de pestivírus, VAC1 induziu títulos ≥60 contra 4/7 BVDV-1 mas contra nenhum isolado de BVDV-2/HoBiPeV; VAC2 induziu títulos protetores contra 4/7 BVDV-1; 10/10 BVDV-2 e 2/8 HoBiPeV; VAC3 induziu títulos protetores contra todos BVDV-1, BVDV-2 e HoBiPeV. Esses resultados indicam que vacinas contendo apenas BVDV-1 BVDV-2, especialmente aquelas inativadas, podem não conferir resposta sorológica protetora contra vários isolados de HoBiPeV. Portanto, a necessidade de se incluir cepas de HoBiPeV nas vacinas deve ser considerada.(AU)

Learning from combination HIV prevention programmes to face COVID-19 emerging pandemic / Aprender de los programas combinados de prevención del VIH para enfrentar la pandemia emergente COVID-19

Abstract Before a vaccine against SARS-CoV-2 became available, several measures to control COVID-19 pandemic are necessary. Analogously, in the absence of an available vaccine, Combination HIV Prevention Programmes have consolidated a large experience of biomedical, behavioral and structural interventions suitable for several epidemiological settings. Adaptation of such experiences can organize mid-term and long-term responses to face COVID-19.

Resumen Antes de que se disponga de una vacuna contra el SARS-CoV-2, son necesarias varias medidas para controlar la pandemia de COVID-19. En forma análoga, en ausencia de una vacuna disponible, los Programas de Prevención del VIH combinados han consolidado una gran experiencia de intervenciones biomédicas, conductuales y estructurales adecuadas para varios entornos epidemiológicos. La adaptación de estas experiencias puede organizar respuestas a mediano y largo plazo para hacer frente a la epidemia de COVID-19.

COVID-19: respuesta inmune y perspectivas terapéuticas

RESUMEN La enfermedad causada por el nuevo coronavirus (COVID-19) se caracteriza por presentar fiebre y tos, afectar el tracto respiratorio inferior y estar asociada con la edad, comorbilidades y un sistema inmune debilitado. Típicamente se ha evidenciado linfopenias en los casos graves y una desmedida producción de citocinas inflamatorias (tormenta de citocinas), lo que explicaría el rol de la respuesta hiperinflamatoria en la patogénesis de la COVID-19. Las respuestas inflamatorias secundarias por reinfecciones del virus podrían inducir el aumento o la mejora dependiente de anticuerpos (ADE, por sus siglas en inglés), un fenómeno virémico que podría ser un mecanismo alternativo de infección celular y que se deberá tener en cuenta cuando se diseñen vacunas o inmunoterapias que involucren el estímulo de anticuerpos neutralizantes o el uso de anticuerpos monoclonales. Actualmente no existen vacunas ni tratamientos que demuestren seguridad y eficacia en pacientes con COVID-19; sin embargo, se espera la conclusión de los resultados de la aplicación de una vacuna de ácidos nucleicos ARNm (mensajero del ácido ribonucleico) y de un fármaco antiviral (remdisivir) que se encuentran en ensayos clínicos fase III. Por el momento la mejor medida para evitar la propagación de la infección es el aislamiento social exhaustivo y viene siendo adoptado por varios países según recomendación de la Organización Mundial de la Salud (OMS).

ABSTRACT Disease caused by the new coronavirus (COVID-19) is characterized by fever, cough, and affection of the lower respiratory tract. It is associated with age, comorbidities and a weakened immune system. Typically, lymphopenias have been evidenced in severe cases and an excessive production of inflammatory cytokines (cytokine storm), which would explain the role of the hyperinflammatory response in the pathogenesis of COVID-19. Secondary inflammatory responses from virus reinfections may induce antibody-dependent enhancement (ADE), a viremic phenomenon that may be an alternative mechanism of cellular infection and should be considered when designing vaccines or immunotherapies involving the stimulation of neutralizing antibodies or the use of monoclonal antibodies. Currently, no vaccines or treatments demonstrate safety and efficacy in patients with COVID-19. However, the results from phase III clinical trials which involve the application of an mRNA (messenger ribonucleic acid) nucleic acid vaccine and an antiviral drug (remdisivir), are yet to be concluded. For the time being, the best measure to prevent the spread of COVID-19 is by implementing social isolation, this measure has been adopted by several countries as recommended by the World Health Organization (WHO).

Vacinas Anticovid: um Olhar da Saúde Coletiva / Anti-Covid vaccines: a look from the Collective Health

Resumo O artigo discute a complexidade da pandemia destacando as várias dimensões, intrínsecas e extrínsecas envolvidas no desenvolvimento das vacinas contra o SARS-CoV-2, com ênfase nos dois produtos mais avançados no campo dos testes clínicos. São eles, a vacina desenvolvida pela Universidade de Oxford associada à farmacêutica britânica AstraZeneca e a desenvolvida pela empresa chinesa Sinovac. Essa escolha deriva também do fato das duas estarem com atividades de testagem e, caso bem-sucedidas, com futura produção no Brasil, respectivamente pelo Bio-Manguinhos, na Fiocruz, e pelo Instituto Butantã, em São Paulo. Do ponto de vista conceitual, o artigo parte da reflexão oriunda do campo da Saúde Coletiva que trata das fronteiras entre o biológico e o social. Procura ainda demonstrar que, caso sejam bem sucedidas, as vacinas, muito embora importantes ferramentas para o enfrentamento da pandemia, não dispensarão a continuidade de outras medidas não farmacológicas já utilizadas.

Abstract The paper discusses the complex nature of the pandemic by highlighting the various intrinsic and extrinsic dimensions in the development of SARS-CoV-2 vaccines, with an emphasis on the two most advanced products in clinical testing, namely, the vaccine developed by the University of Oxford associated with the British pharmaceutical company AstraZeneca, and the one developed by Chinese company Sinovac. This choice also stems from the fact that both have testing activities, which, if successful, will lead to future production in Brazil, by Bio-Manguinhos/Fiocruz, Rio de Janeiro, and the Butantã Institute, in São Paulo, respectively. From a conceptual viewpoint, this paper builds on the reflection from the field of Collective Health that addresses the boundaries between the biological and the social spheres. It also seeks to show that, if successful and while important tools for coping with the pandemic, vaccines will not dispense with the continuity of other non-pharmacological measures already used.

Evaluation of Immune Responses and Histopathological Effects against Gamma Irradiated Avian Influenza (Sub type H9N2) Vaccine on Broiler Chicken

Abstract Vaccination is a good strategy for the prevention of avian influenza virus. In this research Gamma Irradiated Avian Influenza (Sub type H9N2) Vaccine (GAIV) was prepared by 30 kGy irradiation and used for vaccination of broiler chickens. The purpose was a comparison of immune responses in the two routes of administration for the GAIV vaccine; intranasal and subcutaneously, use of Montanide ISA70 and Trehalose accompanied with irradiated vaccine and compare with formalin vaccine. The Influenza Virus A/Chicken/IRN/Ghazvin/2001/H9N2 was irradiated and used for vaccine formulation, and formalin inactivated AIV was used as conventional vaccine. Chickens were vaccinated by GAIV with and without Trehalose, GAIV and formalin vaccines with ISA70, two routes of administration were intranasal and subcutaneously. All the vaccinated chickens showed a significant increase in antibody titration. The most significant increase of antibody titration was in irradiated vaccine plus Trehalose groups intranasal and subcutaneously. After the first and second intranasal vaccination, the amount of IFN-gamma increased in the irradiated vaccine plus Trehalose group compared to other groups. However, most of the vaccinated groups did not show any significant increase of IFN-α concentration. Histopathological examination revealed lymphocyte infiltration (++), foci dispersed of hemorrhage and edema in intranasal vaccination groups and in addition to these, thickening of alveolar septa was observed in the injection groups. GAIV vaccine can be a good candidate for vaccine preparation, and Trehalose as a stabilizer protects viral antigenic proteins, also makes more absorbance of antigen by the inhalation route. In vaccinated chickens the ulcers in injected vaccines were lower than intranasal vaccines.

Identification of enteric viruses circulating in a dog population with low vaccine coverage

ABSTRACT Although the use of vaccines has controlled enteric diseases in dogs in many developed countries, vaccine coverage is still under optimal situation in Brazil. There is a large population of nonimmunized dogs and few studies about the identification of the viruses associated with diarrhea. To address this situation, stool samples from 325 dogs were analyzed by polymerase chain reaction for the detection of common enteric viruses such as Canine adenovirus (CAdV), Canine coronavirus (CCoV), Canine distemper virus (CDV), Canine rotavirus (CRV) and Carnivorous protoparvovirus 1 (canine parvovirus 2; CPV-2). At least one of these species was detected in 56.6% (184/325) of the samples. The viruses detected most frequently in either diarrheic or nondiarrheic dog feces were CPV-2 (54.3% of the positive samples), CDV (45.1%) and CCoV (30.4%), followed by CRV (8.2%) and CAdV (4.9%). Only one agent was detected in the majority of the positive samples (63%), but co-infections were present in 37% of the positive samples and mainly included CDV and CPV-2. The data presented herein can improve the clinical knowledge in regions with low vaccine coverage and highlight the need to improve the methods used to control these infectious diseases in domestic dogs.

Dengue, zika, chikungunya y el desarrollo de vacunas / Dengue, zika, chikungunya and the development of vaccines

Dengue (DENV), zika (ZIKV) y chikungunya (CHIKV), tres arbovirosis transmitidas por mosquitos Aedes, se han propagado en las últimas décadas en zonas tropicales y subtropicales húmedas. El dengue es epidémico en áreas subtropicales de la Argentina. Después de la infección por DENV hay inmunidad duradera contra el serotipo infectante, pero aumenta el riesgo de enfermedad grave por los otros tres. La vacuna recombinante tetravalente, Dengvaxia® previene el dengue grave y la hospitalización en sujetos seropositivos. En 2017 se aprobó Dengvaxia en Argentina, para edades de 9 a 45 años, sin incluirla en el calendario nacional de vacunación. Otras dos vacunas se hallan en evaluación Fase III: la desarrollada por NIAID/ Instituto Butantan y la vacuna Takeda. ZIKV, virus asociado a microcefalia en recién nacidos en Brasil, circula desde 2016 en Argentina. Aún no existe vacuna de actividad comprobada contra ZIKV ni tratamiento eficaz. No se registró circulación activa de CHIKV en Argentina en 2017. Los brotes de fiebre CHIKV tienen una complicación: el desarrollo de reumatismo crónico post-enfermedad. No existen vacunas aprobadas para humanos ni terapias antivirales efectivas. La gravedad de estas virosis contribuyó a un rápido progreso en el conocimiento de los procesos de infección y de la respuesta inmune. Pero sus vectores, Aedes aegypti y A. albopictus, continúan expandiéndose, lo que indica que la vacuna será el medio más efectivo para el control. Se resume aquí información sobre estas arbovirosis en Argentina y Brasil, y se describen avances en el desarrollo y la evaluación de vacunas.

Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda.ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

Vaccination coverage in a cohort of HIV-infected patients receiving care at an AIDS outpatient clinic in Espírito Santo, Brazil

Abstract This cross-sectional study assessed the immunization status of human immune deficiency virus (HIV)-infected patients receiving care at an outpatient clinic in Brazil. The sociodemographic characteristics, CD4 count and HIV viral load of 281 out of 612 adult outpatients were analyzed. A total of 331 patients were excluded because of no availability of vaccination cards. Chi-square or Fisher's exact test were used. Immunization coverage was higher for diphtheria/tetanus (59.79%) and hepatitis B (56.7%), and lowest for hepatitis A (6.8%) and for meningococcal group C (6%). Only 11.74% of the patients had received the influenza virus vaccine yearly since their HIV-infection diagnosis. No vaccination against influenza (p < 0.034) or hepatitis B (p < 0.029) were associated with CD4 counts <500 cells/mL; no vaccination against flu or pneumococcus were associated with detectable HIV viral load (p < 0.049 and p < 0.002, respectively). Immunization coverage is still very low among HIV-infected adults in this setting despite recommendations and high infection-related mortality.

Vacunación de pacientes adultos receptores de trasplante de células madre hematopoyéticas: Perspectiva de Costa Rica / Vaccination of adult patients receiving hematopoietic stem cell transplantation: Perspective of Costa Rica

In this article the present recommendations for immunization of adult patients who received hematopoietic stem cell transplantation -a common procedure in therapy of many types of hematological diseases and serious inborn defects of the immune system- are reviewed and discussed. Patients that undergo this kind of transplantation procedure exhibit, compared to the general population, an elevated susceptibility of immune-preventable infections, due to loss of the humoral and cellular protective immunity. A revaccination strategy for transplanted patients can result in a significant diminution of morbidity and mortality related to the treatment of these diseases. Few data are published about the duration and magnitude of the vaccination response in this specific population of patients. Moreover, deviation from international guidelines recommendations for post-transplant immune prophylaxis can be observed frequently, partly as a result of the absence of specific vaccines in some countries. Multiple factors as intensity of the pharmacologic immune suppression, myeloablative regimen, administration of monoclonal and polyclonal antibodies, duration of the post-transplant period or the presence of graft-versus-host disease (GVHD), can influence the immune response and establish special considerations for certain biological agents, as observed in case of living attenuated virus composed vaccines. This conditions are responsible for the fact that an optimal time point for vaccination of transplanted patients remains not clearly defined. More specific studies about the underlying immunological mechanisms during immunocompromised periods are necessary to understand better the immunogenicity and security of existing vaccines. The development of innovative vaccines as well can induce certain advances in the post-transplant therapy.

El presente artículo revisa las recomendaciones actuales para la inmunización de pacientes adultos que han recibido trasplante de células madre hematopoyéticas, procedimiento común en la terapia de muchas patologías hematológicas y defectos congénitos del sistema inmune. Los pacientes que reciben este tipo de tratamiento son más susceptibles a infecciones inmunoprevenibles que la población general debido a la pérdida de la inmunidad protectora tanto humoral como celular con posterioridad al trasplante. De esta manera, la revacunación de los receptores de trasplante representa una estrategia importante para reducir la morbilidad y mortalidad asociadas con esas enfermedades. Sin embargo, se conoce poco sobre la duración y magnitud de la respuesta inmunológica generada por las vacunas en esta población. Además, aunque existen guías internacionales consensuadas en inmunoprofilaxis post-trasplante, frecuentemente ocurren desviaciones en las prácticas recomendadas por múltiples motivos, incluyendo la no disponibilidad de ciertas vacunas en algunos sistemas de salud. Factores como la intensidad de la inmunosupresión farmacológica, el régimen mieloablativo empleado, la administración de anticuerpos monoclonales y policlonales, la duración de la fase neutropénica en el período posterior al trasplante y la presencia de enfermedad injerto versus hospedero (graft-versus-host disease, GVHD) pueden influenciar la respuesta inmunitaria y establecer consideraciones especiales para ciertos agentes como es el caso de las vacunas compuestas por virus vivos atenuados. Estas condiciones contribuyen a que el momento oportuno de inicio de las inmunizaciones en los receptores de trasplante aún no se encuentre bien definido. Se requieren más estudios específicos acerca de los mecanismos inmunológicos subyacentes durante los estados de inmunocompromiso para entender mejor la inmunogenicidad y seguridad de las vacunas existentes en dichos contextos. El desarrollo de vacunas innovadoras puede también inducir avances en la terapia post-trasplante.

Association of the time that elapsed from last vaccination with protective effectiveness against foot-and-mouth disease in small ruminants

Routine and emergency vaccination of small ruminants against foot-and-mouth disease (FMD) is mandatory in many endemic countries, yet data on the field effectiveness of the vaccines used is scarce. We conducted an investigation of a serotype O FMD outbreak that took place in a sheep and goat pen, and estimated the effectiveness of various routine vaccination statuses. We also evaluated the protection provided by colostrum administration and emergency vaccination. Animals which were routinely vaccinated twice were not clinically affected while disease incidence was observed among animals routinely vaccinated only once (p = 0.004 according to a two-sided Fisher's exact test). In groups vaccinated only once, there was a significant association between the average time that elapsed since last vaccination and the disease incidence (n = 5; Spearman correlation coefficient: r(s) = 1.0, p < 0.01). In addition, non-vaccinated lambs fed colostrum from dams vaccinated more than 2 months before parturition had a mortality rate of 33%. Administration of emergency vaccination 2 days after the occurrence of the index case was the probable reason for the rapid blocking of the FMD spread within 6 days from its onset in the pen.

Recombinant Kluyveromyces lactis expressing highly pathogenic porcine reproductive and respiratory syndrome virus GP5 elicits mucosal and cell-mediated immune responses in mice

Currently, killed-virus and modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are used to control porcine reproductive and respiratory syndrome. However, both types of vaccines have inherent drawbacks; accordingly, the development of novel PRRSV vaccines is urgently needed. Previous studies have suggested that yeast possesses adjuvant activities, and it has been used as an expression vehicle to elicit immune responses to foreign antigens. In this report, recombinant Kluyveromyces lactis expressing GP5 of HP-PRRSV (Yeast-GP5) was generated and immune responses to this construct were analyzed in mice. Intestinal mucosal PRRSV-specific sIgA antibody and higher levels of IFN-gamma in spleen CD4+ and CD8+ T cells were induced by oral administration of Yeast-GP5. Additionally, Yeast-GP5 administered subcutaneously evoked vigorous cell-mediated immunity, and PRRSV-specific lymphocyte proliferation and IFN-gamma secretion were detected in the splenocytes of mice. These results suggest that Yeast-GP5 has the potential for use as a vaccine for PRRSV in the future.

Enhancing mucosal immunity in mice by recombinant adenovirus expressing major epitopes of porcine circovirus-2 capsid protein delivered with cytosine-phosphate-guanosine oligodeoxynucleotides

A recombinant replication-defective adenovirus expressing the major epitopes of porcine circovirus-2 (PCV-2) capsid protein (rAd/Cap/518) was previously constructed and shown to induce mucosal immunity in mice following intranasal delivery. In the present study, immune responses induced by intranasal immunization with a combination of rAd/Cap/518 and cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) were evaluated in mice. The levels of PCV-2-specific IgG in serum and IgA in saliva, lung, and intestinal fluids were significantly higher in the group immunized with rAd/Cap/518 and CpG ODN than animals immunized with rAd/Cap/518 alone. The frequencies of IL-2-secreting CD4+ T cells and IFN-gamma-producing CD8+ T cells were significantly higher in the combined immunization group than mice immunized with rAd/Cap/518 alone. The frequencies of CD3+, CD3+CD4+CD8-, and CD3+CD4-CD8+ T cells in the combined immunization group were similar to that treated with CpG ODN alone, but significantly higher than mice that did not receive CpG ODN. PCV-2 load after challenge in the combined immunization group was significantly lower than that in the phosphate-buffered saline placebo group and approximately 7-fold lower in the group treated with CpG ODN alone. These results indicate that rAd/Cap/518 combined with CpG ODN can enhance systemic and local mucosal immunity in mice, and represent a promising synergetic mucosal vaccine against PCV-2.

Antigen targeting to M cells for enhancing the efficacy of mucosal vaccines

Vaccination is one of the most successful applications of immunology and for a long time has depended on parenteral administration protocols. However, recent studies have pointed to the promise of mucosal vaccination because of its ease, economy and efficiency in inducing an immune response not only systemically, but also in the mucosal compartment where many pathogenic infections are initiated. However, successful mucosal vaccination requires the help of an adjuvant for the efficient delivery of vaccine material into the mucosa and the breaking of the tolerogenic environment, especially in oral mucosal immunization. Given that M cells are the main gateway to take up luminal antigens and initiate antigen-specific immune responses, understanding the role and characteristics of M cells is crucial for the development of successful mucosal vaccines. Especially, particular interest has been focused on the regulation of the tolerogenic mucosal microenvironment and the introduction of the luminal antigen into the lymphoid organ by exploiting the molecules of M cells. Here, we review the characteristics of M cells and the immune regulatory factors in mucosa that can be exploited for mucosal vaccine delivery and mucosal immune regulation.

Cellular responses in the respiratory tract following intranasal administration of peste des petits ruminant vaccine in goats / Respuestas celulares en el tracto respiratorio después de la administración intranasal de la vacuna contra la peste de pequeños rumiantes en cabras

A trial was conducted to compare the cellular responses in the respiratory tract in intranasal vaccination against caprine Peste des petits ruminant lineage 1 variant virus infection with intramuscular and subcutaneous vaccinations in order to elucidate the mechanism of the protection. Twenty four goats were divided into four equal groups. Group 1 was vaccinated intranasaly, group 2 was vaccinated subcutaneously, and group 3 intramuscularly, while Group 4 was the unvaccinated control group. In each group the vaccinations were carried out once. All goats were challenged intratrachealy with PPR virus at a concentration of 106.5 TCID50 two weeks after vaccination and were euthanised 21 days after the challenge. The bronchoalveolar lavage differential count, bronchial associated lymphoid tissue (BALT) responses were measured using standard techniques. Descriptive Statistics and ANOVA was employed and significance was at p < 0.05. The exposure also resulted into significant increase in the number and size of BALT as well as the number of lymphocytes in BALT. This study showed the mechanism of the protective effect of intranasal vaccination of PPR vaccine observed with the strong mucosal and defensive cellular responses in the respiratory tract observed than the subcutaneous and intramuscular routes.

Se realizó un ensayo para comparar las respuestas celulares en las vías respiratorias después de la vacunación intranasal contra la variante caprina de la infección del virus peste de pequeños rumiantes linaje 1 con vacunas intramusculares y subcutáneas con el fin de dilucidar el mecanismo de protección. Veinticuatro cabras fueron divididas en cuatro grupos iguales. El Grupo 1 fue vacunado por vía intranasal, el grupo 2 vía subcutánea, el grupo 3 vía intramuscular y el grupo 4 control no vacunado. En cada grupo se vacunó sólo una vez. Todas las cabras fueron expuestas al virus peste de pequeños rumiantes por vía intratraqueal a una concentración de 106.5 TCID50 2 semanas después de la vacunación, y fueron sometidos a eutanasia 21 días después. Se midieron el recuento diferencial del lavado broncoalveolar y las respuestas de los tejidos linfoides asociados bronquios (BALT) utilizando técnicas estándar. Los resultados se evaluaron por estadística descriptiva y ANOVA, con una significación p<0,05. La exposición también mostró un aumento significativo en el número y tamaño del BALT, así como el número de linfocitos en este. El estudio mostró que el mecanismo del efecto protector de la vacunación intranasal contra el virus peste de pequeños rumiantes posee una respuesta mucosa y celular defensiva en el tracto respiratorio mayor que la observada por vacunación vía subcutánea e intramuscular.

VPH / HPV

Actualmente la Administración de drogas y Alimentos (FdA) de estados unidos aprobó dos vacunas para prevenir la infección por vPh (virus de Papiloma humano): Gardasil® (vacuna tetravalente) y cervarix ® (vacuna bivalente). Ambas vacunas son muy efectivas en la prevención de infecciones persistentes por los tipos 16 y 18 de vPh, dos de los vPh de “alto riesgo” que causan la mayoría (70%) delos cánceres de cuello uterino y en menor porcentaje de cáncer de ano y pene. Gardasil® impide también la infección por los tipos 6 y 11 de vPh, los cuales causan prácticamente todas (90%) las verrugas genitales. se presenta un resumen de la inmunogenicidad, eficacia, indicaciones, modo de empleo y presentaciones comerciales de estas dos vacunas

the Food and drug Administration (FdA) of usA licensed two vaccines for the prevention of vPh (human Papillomavirus) infection: Gardasil® (quadrivalent vaccine) and cervarix® (bivalent vaccine). Both vaccines are very effective in the prevention of persistent infection by serotypes 16 and 18 of vPh, two of the “high risk” vPh, which cause 70% of cervical cancers and in low percentages anal and penile cancers. Gardasil® prevents infection by serotytpes 6 and 11, which cause almost all (90%) of genital warts.this review presents the immunogenicity, efficacy, recommendations, doses, administration and commercial presentation of bothvaccines

Avaliação de diferentes vias vacinais para vacinação contra o vírus da doença de Newcastle em aves de fundo de quintal / Assessment of different vaccination approaches against Newcastle disease virus in domestic backyard poultry

Foram avaliadas três vias de aplicação vacinal contra o vírus da doença de Newcastle em aves de criatório de fundo de quintal (AFQ) jovens e adultas. Um total de 135 AFQ foram distribuídas em tratamentos distintos de acordo com a via vacinal: via ocular (VO), água de bebida (VAB) e alimentar (VA). Cada tratamento foi representado por 40 aves (20 jovens e 20 adultas) e utilizou-se um grupo-controle de 15 aves não vacinadas. O programa de vacinação estabelecido constou de uma primovacinação e dois reforços vacinais, utilizando-se a cepa La Sota. Para aves jovens, os títulos obtidos pelas VO e VAB não diferiram aos 15, 45 e 140 dias, mas houve diferenças nos títulos das aves vacinadas pela VA. Nas aves adultas, a vacinação pela VO apresentou resultados mais elevados que as vacinações pelas VAB e VA na primeira resposta, aos 15 dias. Aos 45 dias, os títulos obtidos pela VAB foram mais baixos que os obtidos pela VO, e, aos 140 dias, não houve diferença entre as três vias avaliadas. Concluiu-se que as vacinações pelas VO e VAB constituem alternativas eficazes para vacinação de AFQ jovens e adultas.

Three ways of vaccination against Newcastle Disease Virus (NDV) were evaluated in young and adults domestic backyard poultry (DBP). A total of 135 DBP was submitted to three different administration routes of ND vaccine: eye-drop, drinking water, and feed. Each treatment consisted of 40 birds (20 young and 20 adult) and a control group of 15 unvaccinated birds. The treatment consisted of a first vaccination and two boosters, using La Sota strain. For young birds, the eye-drop and drinking water vaccinations presented no differences at 15, 45, and 140 days, differing from the titers obtained by birds treated by feed vaccination method. In the adult birds, the eye-drop administration presented higher titers than by drinking water and feed approaches in the first response to the vaccination at 15 days. At 45 days, the results obtained by the drinking water had lower titers than those from the eye-drop. The three vaccination methods presented no difference at 140 days. In conclusion, the vaccination by eye-drop and drinking water methods constituted an efficient alternative of vaccination for adult and young DBP against Newcastle virus.

Protection of chicken against very virulent IBDV provided by in ovo priming with DNA vaccine and boosting with killed vaccine and the adjuvant effects of plasmid-encoded chicken interleukin-2 and interferon-gamma

The aim of this study was to examine the efficacy of in ovo prime-boost vaccination against infectious bursal disease virus (IBDV) using a DNA vaccine to prime in ovo followed by a killed-vaccine boost post hatching. In addition, the adjuvant effects of plasmid-encoded chicken interleukin-2 and chicken interferon-gamma were tested in conjunction with the vaccine. A plasmid DNA vaccine (pcDNA-VP243) encoding the VP2, VP4, and VP3 proteins of the very virulent IBDV (vvIBDV) SH/92 strain was injected into the amniotic sac alone or in combination with a plasmid encoding chicken IL-2 (ChIL-2) or chicken IFN-gamma (ChIFN-gamma) at embryonation day 18, followed by an intramuscular injection of a commercial killed IBD vaccine at 1 week of age. The chickens were orally challenged with the vvIBDV SH/92 strain at 3 weeks of age and observed for 10 days. In ovo DNA immunization followed by a killed-vaccine boost provided significantly better immunity than the other options. No mortality was observed in this group after a challenge with the vvIBDV. The prime-boost strategy was moderately effective against bursal damage, which was measured by the bursa weight/body weight ratio, the presence of IBDV RNA, and the bursal lesion score. In ovo DNA vaccination with no boost did not provide sufficient immunity, and the addition of ChIL-2 or ChIFN-gamma did not enhance protective immunity. In the ConA-induced lymphocyte proliferation assay of peripheral blood lymphocyte collected 10 days post-challenge, there was greater proliferation responses in the DNA vaccine plus boost and DNA vaccine with ChIL-2 plus boost groups compared to the other groups. These findings suggest that priming with DNA vaccine and boosting with killed vaccine is an effective strategy for protecting chickens against vvIBDV.