Assuntos
COVID-19 , Máscaras , Pandemias , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Instalações de SaúdeRESUMO
Here we describe as a potential vaccine candidate a replication-defective HIV that encodes multiple viral genes in addition to a cassette that includes both truncated cyclin T1 and an autofluorescent protein. After confirming functionality of the cyclin T1, we immunized mice intramuscularly once or twice with the replication-defective HIV vector pseudotyped with vesicular stomatitis virus (VSV) G protein (RD HIV), a plasmid encoding CMV-driven gag (gag DNA), or adenovirus gag (Ad5-gag). Capsid-specific antibody titers following RD HIV immunization were >10(6)/ml and approximately equivalent to those induced by gag DNA and Ad5-gag. Antibodies against the autofluorescent protein and VSV G were also detected. After RD HIV immunization ELISpot assays demonstrated Gag-specific interferon-gamma (IFN-gamma) SFU equivalent to that of Ad5-gag and fourfold greater than that of gag DNA. HIV polymerase-specific IFN-gamma SFU values were similar, and boosting increased both antibody titers and the IFN-gamma response. Challenge using vaccinia virus (VV)-gag demonstrated significantly lower recoverable VV for RD HIV-immunized mice compared to controls. No significant differences were observed in vaccinated mice challenged with wild-type VV. This study demonstrates the efficacy of RD HIV in conferring HIV-specific immunity and protection in mice and suggests its potential use in humans as either a prophylactic or a therapeutic vaccine.
Assuntos
Vacinas contra a AIDS/imunologia , Produtos do Gene gag/imunologia , HIV/imunologia , Vaccinia virus/imunologia , Replicação Viral , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Adenoviridae/genética , Adenoviridae/imunologia , Animais , Anticorpos Antivirais/sangue , Formação de Anticorpos , Ciclina T , Ciclinas/genética , Citomegalovirus/genética , Citomegalovirus/imunologia , Vetores Genéticos/imunologia , HIV/genética , Humanos , Imunidade Celular , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Camundongos , Vacinação , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologiaRESUMO
The management of antiretroviral-experienced and -naive HIV-infected patients is becoming increasingly complex with the emergence of multidrug-resistant viruses and with the inter-relationships between numerous virological, immunological and therapeutic factors. In addition to standard surrogate markers of peripheral CD4+ T-cell counts and plasma viral loads, viral resistance phenotype, replication capacity and genotype assays serve as objective measures of viral properties, which presumably reflect, to a certain degree, what is occurring in vivo. This review explores the principles behind, and the basic science and clinical evidence supporting the application of viral resistance phenotypic assays and replication capacity assays in the therapeutic management of HIV disease.