RESUMEN
During the 2009 H1N1 influenza virus pandemic (pdmH1N1) outbreak, it was found that most individuals lacked antibodies against the new pdmH1N1 virus, and only the elderly showed anti-hemagglutinin (anti-HA) antibodies that were cross-reactive with the new strains. Different studies have demonstrated that prior contact with the virus can confer protection against strains with some degree of dissimilarity; however, this has not been sufficiently explored within the context of a pdmH1N1 virus infection. In this study, we have found that a first infection with the A/Brisbane/59/2007 virus strain confers heterologous protection in ferrets and mice against a subsequent pdmH1N1 (A/Mexico/4108/2009) virus infection through a cross-reactive but non-neutralizing antibody mechanism. Heterologous immunity is abrogated in B cell-deficient mice but maintained in CD8(-/-) and perforin-1(-/-) mice. We identified cross-reactive antibodies from A/Brisbane/59/2007 sera that recognize non-HA epitopes in pdmH1N1 virus. Passive serum transfer showed that cross-reactive sH1N1-induced antibodies conferred protection in naive recipient mice during pdmH1N1 virus challenge. The presence or absence of anti-HA antibodies, therefore, is not the sole indicator of the effectiveness of protective cross-reactive antibody immunity. Measurement of additional antibody repertoires targeting the non-HA antigens of influenza virus should be taken into consideration in assessing protection and immunization strategies. We propose that preexisting cross-protective non-HA antibody immunity may have had an overall protective effect during the 2009 pdmH1N1 outbreak, thereby reducing disease severity in human infections.
Asunto(s)
Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Antígenos CD8/inmunología , Protección Cruzada , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Embrión de Pollo , Femenino , Hurones , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , México/epidemiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , PandemiasRESUMEN
The use of ribavirin in influenza treatment is a matter of debate. Due to adamantine- and oseltamivir-resistant strains of the current pandemic H1N1 (pdmH1N1) influenza viruses, the demand for alternative antiviral treatments has increased. This study demonstrated the potent antiviral effects of ribavirin in a mouse model of pdmH1N1 influenza infection (A/Mexico/4108/2009). It was found that treatment with 40 mg ribavirin kg⻹ day⻹ partially protected the animals if initiated immediately upon infection. Administration of similar concentrations on subsequent days or immediate therapy with lower doses efficiently delayed disease progression. Correlation studies showed a direct relationship between low viral titres in the lung during the early stages of infection with animal survival in ribavirin-treated animals. Reduced lung pathology in animals treated with ribavirin following infection also indicated the importance of immediate treatment. This study revealed the antiviral properties of ribavirin and these results justify comprehensive clinical studies for the use of ribavirin against influenza virus in future outbreaks.
Asunto(s)
Antivirales/administración & dosificación , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Ribavirina/administración & dosificación , Animales , Antivirales/farmacología , Embrión de Pollo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Pulmón/patología , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Ribavirina/farmacología , Análisis de SupervivenciaRESUMEN
Reminiscent of the Severe Acquired Respiratory Syndrome (SARS) outbreak during the spring and fall of 2003, an outbreak of Severe Respiratory Illness (SRI) in Mexico has world health officials in a state of concern. The concern centers on the fact that as of April 24, 2009 over 134 cases have been reported in Mexico with an accompanying high mortality rate in healthy young adults. With new information surfacing from public health investigations of recent cases of swine influenza in the United States, here we discuss putative links between the outbreak of SRI in Mexico and the emergence of a novel swine influenza A (H1N1) strain in several southwestern U.S. states.