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1.
Mol Ther Methods Clin Dev ; 30: 194-207, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37502665

RESUMO

Because of continual generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to design the next generation of vaccines to combat the threat posed by SARS-CoV-2 variants. We developed human adenovirus (HAd) vector-based vaccines (HAd-Spike/C5 and HAd-Spike) that express the whole Spike (S) protein of SARS-CoV-2 with or without autophagy-inducing peptide C5 (AIP-C5), respectively. Mice or golden Syrian hamsters immunized intranasally (i.n.) with HAd-Spike/C5 induced similar levels of S-specific humoral immune responses and significantly higher levels of S-specific cell-mediated immune (CMI) responses compared with HAd-Spike vaccinated groups. These results indicated that inclusion of AIP-C5 induced enhanced S-specific CMI responses and similar levels of virus-neutralizing titers against SARS-CoV-2 variants. To investigate the protection efficacy, golden Syrian hamsters immunized i.n. either with HAd-Spike/C5 or HAd-Spike were challenged with SARS-CoV-2. The lungs and nasal turbinates were collected 3, 5, 7, and 14 days post challenge. Significant reductions in morbidity, virus titers, and lung histopathological scores were observed in immunized groups compared with the mock- or empty vector-inoculated groups. Overall, slightly better protection was seen in the HAd-Spike/C5 group compared with the HAd-Spike group.

2.
J Infect ; 80(1): 111-115, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31738944

RESUMO

OBJECTIVES: Although primarily transmitted by Aedes aegypti mosquitos, Zika virus (ZIKV) can also be transmitted by blood transfusion, due to the fact that some of the infected donors can establish asymptomatic viremia. ZIKV seroprevalence in Brazilian blood donors is unknown. The main reason for this gap in the knowledge originates from the difficulty in evaluating ZIKV humoral immunity due to antigenic cross-reactivity between the different Brazilian flaviviruses and, in particular, dengue virus (DENV). The objective of this study was to evaluate the anti-ZIKV IgG prevalence in blood donors from the Northeast region of the São Paulo State, Brazil, which experienced a ZIKV outbreak in 2016. METHODS: We evaluated the ZIKV seroprevalence using the NS1 anti-ZIKV IgG test (Euroimmun), followed by confirmation of the positive and borderline results using the Plaque Reduction Neutralization Test (PRNT). ZIKV seroprevalence was estimated by testing plasma samples collected in 2015 (before the ZIKV outbreak), 2016 (during the outbreak) and 2017 (after the outbreak). In order to investigate possible antigenic cross - reactivity between ZIKV and DENV we also included samples that were taken well before the ZIKV outbreak, in years 2010 and 2013. RESULTS: The results obtained by the Euroimmun anti-ZIKV IgG test demonstrated ZIKV seroreactivity in 2015, 2016, and 2017 with prevalences of 5.3%, 12.8% and 13.2%, respectively. The inclusion of blood donor samples from 2010 to 2013, demonstrated anti-ZIKV IgG reactivity only for 2013 (1.7%). The PRNT testing of the ZIKV positive and borderline ELISA reacting samples generated positive results only for the years of 2016 and 2017 (prevalences of 5.6% and 9.1%) which coincided with the introduction of ZIKV in our region. CONCLUSIONS: Our results estimate for the first time the ZIKV seroprevalence among Brazilian blood donors from a region with apparently extensive ZIKV circulation and which, at the same time, is highly endemic for DENV. We detected relatively low ZIKV seroprevalence in blood donors from the studied region probably due to the lower intensity of the outbreak compared to other Brazilian locations. Our study adds to the global understanding of ZIKV circulation and the herd immunity of the exposed population.


Assuntos
Dengue , Infecção por Zika virus , Zika virus , Anticorpos Antivirais , Doadores de Sangue , Brasil/epidemiologia , Humanos , Imunoglobulina G , Estudos Soroepidemiológicos , Infecção por Zika virus/epidemiologia
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