RESUMEN
The NYVAC poxvirus vector is used as vaccine candidate for HIV and other diseases, although there is only limited experimental information on its immunogenicity and effectiveness for use against human pathogens. Here we defined the selective advantage of NYVAC vectors in a mouse model by comparing the immune responses and protection induced by vectors that express the LACK (Leishmania-activated C-kinase antigen), alone or with insertion of the viral host range gene C7L that allows the virus to replicate in human cells. Using DNA prime/virus boost protocols, we show that replication-competent NYVAC-LACK that expresses C7L (NYVAC-LACK-C7L) induced higher-magnitude polyfunctional CD8(+) and CD4(+) primary adaptive and effector memory T cell responses (IFNγ, TNFα, IL-2, CD107a) to LACK antigen than non-replicating NYVAC-LACK. Compared to NYVAC-LACK, the NYVAC-LACK-C7L-induced CD8(+) T cell population also showed higher proliferation when stimulated with LACK antigen. After a challenge by subcutaneous Leishmania major metacyclic promastigotes, NYVAC-LACK-C7L-vaccinated mouse groups showed greater protection than the NYVAC-LACK-vaccinated group. Our results indicate that the type and potency of immune responses induced by LACK-expressing NYVAC vectors is improved by insertion of the C7L gene, and that a replication-competent vector as a vaccine renders greater protection against a human pathogen than a non-replicating vector.
Asunto(s)
Vectores Genéticos/inmunología , Leishmania major/efectos de los fármacos , Vacunas contra la Leishmaniasis/administración & dosificación , Leishmaniasis Cutánea/prevención & control , Linfocitos T/efectos de los fármacos , Proteínas Virales/genética , Animales , Antígenos de Protozoos/genética , Antígenos de Protozoos/inmunología , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Vectores Genéticos/química , Células HeLa , Humanos , Inmunización Secundaria , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Leishmania major/genética , Leishmania major/inmunología , Vacunas contra la Leishmaniasis/biosíntesis , Vacunas contra la Leishmaniasis/genética , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Proteínas de Membrana de los Lisosomas/genética , Proteínas de Membrana de los Lisosomas/inmunología , Ratones , Ratones Endogámicos BALB C , Proteínas Protozoarias/genética , Proteínas Protozoarias/inmunología , Linfocitos T/inmunología , Linfocitos T/parasitología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Virus Vaccinia/genética , Virus Vaccinia/inmunología , Proteínas Virales/inmunología , Replicación ViralRESUMEN
One hundred and sixty 1-month-old turkey poults were delivered to 40 households in four communities of the State of Yucatan, Mexico. The poults were divided into two populations, one vaccinated and the other non-vaccinated against avian pox. During three months, monthly visits were carried out in order to monitor the appearance of lesions suggesting avian pox in the birds delivered. Each turkey was clinically examined, searching for characteristic avian pox lesions that were classified according to the degree of severity observed. The true incidence rate and the cumulative incidence rate of avian pox were determined and the true incidence and cumulative incidence rates of mortality were determined and the relative risks calculated. The true incidence rates for avian pox in vaccinated and non-vaccinated birds were 1.5 and 1.47 respectively. The cumulative incidence rates were 0.94 and 0.90 for vaccinated and non-vaccinated birds, respectively. The comparison for the whole period between vaccinated and non-vaccinated groups did not show a significant statistical difference for mortality. However, when mortality was compared between vaccinated and non-vaccinated turkeys for each month of the study, there was a statistically significant difference for the first month (relative risk = 0.216, confidence interval 0.069 to 0.676). In addition, when the severity of pox lesions between groups was compared, statistically significant differences were found in favour of the vaccinated birds (P < 0.0001).
Asunto(s)
Avipoxvirus/inmunología , Enfermedades de las Aves de Corral/epidemiología , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/virología , Infecciones por Poxviridae/veterinaria , Pavos , Vacunas Virales/farmacología , Animales , Incidencia , México/epidemiología , Infecciones por Poxviridae/epidemiología , Infecciones por Poxviridae/prevención & control , Medición de RiesgoRESUMEN
The HIV epidemic in Argentina is characterized by the high prevalence of infections caused by subtype B and BF variants. In this study, the Nef protein was used as a tool to study the impact of HIV-1 BF variants in the design of future vaccines. DNA and MVA vectors expressing Nef of the CRF12_BF recombinant form of HIV-1 were generated and characterized. After the administration of single DNAprime/MVAboost immunization schedules in Balb/c mice we found that NefBF delivered from these vectors generated a response of high specificity with low cross-reactivity against subtype B. But, when a more potent response was induced after 3 priming DNA doses and a booster with MVA virus, cross-reactivity against NefB was detected, although of lower magnitude than the NefBF specific. These results will be pivotal for vaccines designs in our region, indicating that antigens from these viral variants must be considered for a future vaccine.