RESUMO
A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naïve baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α(+) and IFN-γ(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naïve baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.
Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacina contra Febre Amarela/imunologia , Febre Amarela/prevenção & controle , Vírus da Febre Amarela/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Brasil , Humanos , Memória Imunológica/imunologia , Interferon gama/sangue , Fator de Necrose Tumoral alfa/sangue , Vacinação , Febre Amarela/virologiaRESUMO
BACKGROUND: Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines. FINDINGS: Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested. CONCLUSIONS: Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.
Assuntos
Anticorpos Antivirais/biossíntese , Vírus da Dengue/imunologia , Nanopartículas , Animais , Vírus da Dengue/crescimento & desenvolvimento , Camundongos , Microscopia Eletrônica de Varredura , Testes de Neutralização , Ensaio de Placa ViralRESUMO
Diagnosis of leprosy is usually made clinically and there are no tests available for the routine laboratory diagnosis of the disease. The aim of this study was to investigate the potential role of chemokines as biologic markers of disease activity. We used an enzyme-linked immunosorbent assay to measure chemokines in plasma of patients with leprosy (LE) and non-infected (NI) individuals. There were significantly greater concentrations of the chemokines CCL3 and CCL11 in plasma of LE patients than in NI individuals. When the use of CCL11 to differentiate LE patients versus NI individuals was evaluated, the area under the receiver-operator-characteristic curve was 0.95 +/- 0.03 (P < 0.0001). In a group of selected individuals, CCL11 was useful in diagnosis of leprosy, thereby suggesting that measurement of this chemokine may be useful as an aid in diagnosing leprosis.