RESUMO
Madariaga virus (MADV) has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June 2017, a fatal MADV infection was confirmed in a community of Darien Province. We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. In addition, by applying a catalytic, force-of-infection (FOI) statistical model to two serosurveys from Darien Province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically. In 2017, MADV and VEEV IgM seroprevalences were 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%, VEEV: 16.8%, Una virus (UNAV): 16.0%, and Mayaro virus: 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households, raising questions about its vectors and enzootic transmission cycles. Insomnia was associated with MADV and VEEV infections, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in Aruza and Mercadeo, respectively. The lack of additional neurological cases suggests that severe MADV and VEEV infections occur only rarely. Our results indicate that over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased-potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially in some locations of eastern Panama.
Assuntos
Encefalomielite Equina do Leste/epidemiologia , Encefalomielite Equina Venezuelana/epidemiologia , Fazendeiros/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Alphavirus/imunologia , Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/fisiopatologia , Animais , Anticorpos Antivirais/imunologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/fisiopatologia , Vírus Chikungunya/imunologia , Criança , Pré-Escolar , Estudos Transversais , Depressão/fisiopatologia , Tontura/fisiopatologia , Vírus da Encefalite Equina do Leste/imunologia , Vírus da Encefalite Equina Venezuelana/imunologia , Encefalomielite Equina do Leste/imunologia , Encefalomielite Equina do Leste/fisiopatologia , Encefalomielite Equina Venezuelana/imunologia , Encefalomielite Equina Venezuelana/fisiopatologia , Doenças Endêmicas , Epidemias , Fadiga/fisiopatologia , Feminino , Habitação/estatística & dados numéricos , Humanos , Imunoglobulina G , Imunoglobulina M , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores/virologia , Panamá/epidemiologia , Vírus da Floresta de Semliki/imunologia , Estudos Soroepidemiológicos , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Adulto JovemRESUMO
Recombinant replicons of Semliki Forest virus (SFV) can be used to induce high-level, transient expression of heterologous proteins in vivo. We constructed infectious but replication-deficient SFV particles carrying recombinant RNA encoding the Brucella abortus translation initiation factor 3 (IF3). The recombinant SFV particles (SFV-IF3 particles) were then evaluated for their ability to induce immune responses and to protect BALB/c mice against a challenge with B. abortus 2308 following vaccination. Animals inoculated with SFV-IF3 developed IF3-specific IgM antibodies at day 14 post-immunization. In vitro stimulation of splenocytes from vaccinated mice with either recombinant IF3 (rIF3) or crude Brucella protein extracts resulted in a T-cell proliferative response and induction of interferon gamma secretion, but not interleukin-4. In addition, mice immunized with SFV-IF3 exhibited a significant level of resistance against challenge with the virulent B. abortus strain 2308 (P<0.01). These findings indicate that an SFV-based vector carrying RNA encoding Brucella IF3 has potential for use as a vaccine to induce protection against B. abortus infections.
Assuntos
Infecções por Alphavirus/imunologia , Fatores de Iniciação em Eucariotos/imunologia , Fator de Iniciação 3 em Procariotos/imunologia , Vírus da Floresta de Semliki/imunologia , Vacinação , Infecções por Alphavirus/prevenção & controle , Animais , Brucella abortus/genética , Fatores de Iniciação em Eucariotos/genética , Engenharia Genética , Imunidade Ativa/genética , Camundongos , Camundongos Endogâmicos BALB C , Fator de Iniciação 3 em Procariotos/genética , Recombinação Genética , Vírus da Floresta de Semliki/patogenicidade , VirulênciaRESUMO
The use of DNA vectors based on the SFV (Semliki Forest virus) replicon have not been reported in the modality of DNA prime virus boost. In the present study, SFV DNA vectors (DNA vectors based on the SFV replicon) bearing the HIV-1 TAB9 multiepitopic polypeptide minigene were evaluated as priming DNA immunogens followed by a recombinant fowlpox expressing the TAB9 mutiepitope (FPTAB9LZ) boost. The results indicated that mice primed with pSFV(k)tab9 and boosted with FPTAB9LZ significantly decreased the HIV-1 recombinant (VVTAB13, a recombinant vaccinia virus expressing the TAB13 multiepitope) vaccinia virus replication, compared with groups given pSFV(k)tab9 vector and FPTAB9LZ virus alone. Additionally, the viral titre in ovary correlated with the number of specific gamma-interferon-secreting T-cells in spleen. These results support the possible use of SFV DNA vectors in prime-boost approaches implemented in therapeutic/prophylactic treatments for infectious diseases such as HIV-1.
Assuntos
DNA Viral/administração & dosagem , Vírus da Varíola das Aves Domésticas/genética , Terapia Genética/métodos , Infecções por HIV/prevenção & controle , Imunização Secundária/métodos , Vírus da Floresta de Semliki/genética , Vacinas de DNA/administração & dosagem , Animais , Terapia Combinada , Feminino , Vírus da Varíola das Aves Domésticas/imunologia , Infecções por HIV/genética , Infecções por HIV/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Floresta de Semliki/imunologia , Resultado do Tratamento , Vacinação/métodos , Vacinas de DNA/imunologiaRESUMO
Complexes of formalinized Venezuelan equine encephalomyelitis (VEE) virus vaccine and specific IgG formed at antigen-antibody equivalence enhanced the immune responses of rhesus monkeys (Macaca mulatta). The predomonant class of antibody elicited by complexes was IgG. In contrast, lower titers of antibody and a more biphasic (IgG-IgM) response were observed after exposure of monkeys to the vaccine alone. In comparison to the response of monkeys primed with antigen, a more rapid secondary response was obtained in monkeys primed with the complexes of antigen and antibody formed at equivalence. A sustained level of protection of 88% was afforded mice 24 hr after immunization with antigen-antibody complexes; development of protection after administration of antigen required eight days to reach this level. Passive protection (80%-100%) was conferred by IgG controls for seven to eight days after immunization. This level of protection was not significantly affected by X-irradiation 24 hr prior to administration of IgG; however, protection in mice similarly irradiated prior to immunization with antigen-antibody complexes was significantly decreased. Early protection afforded by the complexes was not nonspecific (interferon) but was mediated by specific immunologic mechanisms and may be caused by an early formation of IgG.