RESUMO
The live smallpox vaccine was a historical first and highly effective vaccine. However, along with high immunogenicity, the vaccinia virus (VACV) caused serious side effects in vaccinees, sometimes with lethal outcomes. Therefore, after global eradication of smallpox, VACV vaccination was stopped. For this reason, most of the human population worldwide lacks specific immunity against not only smallpox, but also other zoonotic orthopoxviruses. Outbreaks of diseases caused by these viruses have increasingly occurred in humans on different continents. However, use of the classical live VACV vaccine for prevention against these diseases is unacceptable because of potential serious side effects, especially in individuals with suppressed immunity or immunodeficiency (e.g., HIV-infected patients). Therefore, highly attenuated VACV variants that preserve their immunogenicity are needed. This review discusses current ideas about the development of a humoral and cellular immune response to orthopoxvirus infection/vaccination and describes genetic engineering approaches that could be utilized to generate safe and highly immunogenic live VACV vaccines.
RESUMO
The review contains a brief analysis of the results of investigations conducted during 40 years after smallpox eradication and directed to study genomic organization and evolution of variola virus (VARV) and development of modern diagnostics, vaccines and chemotherapies of smallpox and other zoonotic orthopoxviral infections of humans. Taking into account that smallpox vaccination in several cases had adverse side effects, WHO recommended ceasing this vaccination after 1980 in all countries of the world. The result of this decision is that the mankind lost the collective immunity not only to smallpox, but also to other zoonotic orthopoxvirus infections. The ever more frequently recorded human cases of zoonotic orthopoxvirus infections force to renew consideration of the problem of possible smallpox reemergence resulting from natural evolution of these viruses. Analysis of the available archive data on smallpox epidemics, the history of ancient civilizations, and the newest data on the evolutionary relationship of orthopoxviruses has allowed us to hypothesize that VARV could have repeatedly reemerged via evolutionary changes in a zoonotic ancestor virus and then disappeared because of insufficient population size of isolated ancient civilizations. Only the historically last smallpox pandemic continued for a long time and was contained and stopped in the 20th century thanks to the joint efforts of medics and scientists from many countries under the aegis of WHO. Thus, there is no fundamental prohibition on potential reemergence of smallpox or a similar human disease in future in the course of natural evolution of the currently existing zoonotic orthopoxviruses. Correspondingly, it is of the utmost importance to develop and widely adopt state-of-the-art methods for efficient and rapid species-specific diagnosis of all orthopoxvirus species pathogenic for humans, VARV included. It is also most important to develop new safe methods for prevention and therapy of human orthopoxvirus infections.
Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Poxviridae/epidemiologia , Varíola/epidemiologia , Vacinação/métodos , Vírus da Varíola/patogenicidade , Zoonoses/epidemiologia , Animais , Antivirais/uso terapêutico , Benzamidas/uso terapêutico , Búfalos/virologia , Bovinos , Doenças Transmissíveis Emergentes/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/virologia , Evolução Molecular , Cavalos/virologia , Humanos , Imunidade Coletiva , Isoindóis/uso terapêutico , Orthopoxvirus/genética , Orthopoxvirus/imunologia , Orthopoxvirus/patogenicidade , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/prevenção & controle , Infecções por Poxviridae/virologia , Varíola/imunologia , Varíola/prevenção & controle , Varíola/virologia , Vacina Antivariólica/administração & dosagem , Vacina Antivariólica/biossíntese , Vírus da Varíola/genética , Vírus da Varíola/imunologia , Zoonoses/imunologia , Zoonoses/virologiaRESUMO
The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.
RESUMO
A hybrid vaccinia virus expressing a chimeric protein consisting of thymidine kinase and the encephalitogenic determinant, S1, from guinea pig myelin basic protein was constructed. Infection of guinea pigs with the virus resulted in the development of allergic encephalomyelitis.
Assuntos
Encefalomielite Autoimune Experimental/microbiologia , Proteína Básica da Mielina/fisiologia , Timidina Quinase/fisiologia , Proteínas Virais/fisiologia , Animais , Sequência de Bases , Encefalomielite Autoimune Experimental/patologia , Cobaias , Dados de Sequência Molecular , Proteínas Recombinantes/química , Vaccinia virus/química , Vaccinia virus/patogenicidade , Proteínas Virais/químicaAssuntos
Doenças Autoimunes/etiologia , Encefalomielite Autoimune Experimental/etiologia , Vaccinia virus/patogenicidade , Sequência de Aminoácidos , Animais , Doenças Autoimunes/imunologia , DNA Viral/genética , Encefalomielite Autoimune Experimental/imunologia , Vetores Genéticos , Cobaias , Hibridização Genética/genética , Dados de Sequência Molecular , Proteína Básica da Mielina/administração & dosagem , Plasmídeos/genética , Vaccinia virus/genéticaRESUMO
The possibility of using honeycomb moth larvae for titration of nuclear polyhedrosis virus (NPV) infectious DNA and determinations of transfection effectiveness was studied. Honeycomb moth larvae were shown to be a sensitive system for NPV DNA titration. DEAE-dextran used as a protector increased NPV DNA infectivity 1000-fold, LD50 in this instance being 2 X 10(8) molecules per larva. The method of NPV DNA infectivity determinations by the number of larvae with polyhedreae in the fatty tissue is more sensitive than infectivity determinations by the number of dead larvae and permits titrations of low DNA concentrations. The curve of DNA titration in the presence of DEAE-dextran by the number of larvae with polyhedrae in the fatty tissue allows to quantitate native DNA within the range of 0.01 to 5 micrograms/ml.