Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
iScience ; 25(8): 104764, 2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-35982798

RESUMEN

The link between CD4+ T and B cells during immune responses to DENV and ZIKV and their roles in cross-protection during heterologous infection is an active area of research. Here we used CD4+ lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during a tertiary flavivirus infection in macaques. We show that CD4+ depletion in DENV/ZIKV-primed animals followed by DENV resulted in dysregulated adaptive immune responses. We show a delay in DENV-specific IgM/IgG antibody titers and binding and neutralization in the DENV/ZIKV-primed CD4-depleted animals but not in ZIKV/DENV-primed CD4-depleted animals. This study confirms the critical role of CD4+ cells in priming an early effective humoral response during sequential flavivirus infections. Our work here suggests that the order of flavivirus exposure affects the outcome of a tertiary infection. Our findings have implications for understanding the complex flavivirus immune responses and for the development of effective flavivirus vaccines.

2.
Viruses ; 13(12)2021 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-34960674

RESUMEN

The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data show that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After only one vaccine dose, the neutralization capacity expanded to all tested variants in pre-exposed individuals. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose did induce similar neutralizing antibodies against the Delta as against the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/sangre , COVID-19/virología , Hispánicos o Latinos , Humanos , Mutación , Pruebas de Neutralización , Puerto Rico/etnología , SARS-CoV-2/genética , Vacunación
3.
medRxiv ; 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34729566

RESUMEN

The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data shows that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After one vaccine dose, the neutralization capacity expands to all tested variants. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose induced similar neutralizing antibodies against the Delta compared to the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.

4.
medRxiv ; 2021 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-34100029

RESUMEN

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. We also report that serum neutralization capacity correlates with IgG titers, wherein IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) at the earliest tested timepoint. IgA titers were detectable in just 28.81% of subjects, and only 62.71% of subjects had detectable IgM in the first sample despite confirmation of infection by a molecular diagnostic assay. Our data suggests that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from 10 out of the 59 subjects which had received an initial first dose of mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for induction of neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern seen after natural infection, after the second vaccine dose, the total anti-S antibodies titers declined, however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. The decline in anti-S antibody titer, however, was significantly less in pre-exposed individuals, highlighting the potential for natural infection to prime a more robust immune response to the vaccine. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. However, this difference was significant only when neutralizing antibody titers were compared among the two groups. No differences were observed between naturally infected and vaccinated individuals when total anti-S antibodies and IgG titers were measured. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that a functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies. In this context, our results also support standardizing methods of assessing the humoral response to SARS-CoV-2 when determining vaccine efficacy and describing the immune correlates of protection for SARS-CoV-2.

5.
Viruses ; 13(10)2021 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-34696403

RESUMEN

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.


Asunto(s)
Inmunidad Humoral/fisiología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/fisiología , Adulto , Anciano , Anticuerpos Neutralizantes/análisis , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , COVID-19/inmunología , COVID-19/fisiopatología , Vacunas contra la COVID-19/inmunología , Femenino , Estudios de Seguimiento , Humanos , Inmunidad Humoral/genética , Inmunidad Humoral/inmunología , Masculino , Persona de Mediana Edad , Unión Proteica/genética , Dominios Proteicos/genética , Puerto Rico/epidemiología , SARS-CoV-2/patogenicidad , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación
6.
PLoS Negl Trop Dis ; 14(5): e0008285, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32463814

RESUMEN

Little is known about the contribution of virus-specific and cross-reacting antibodies (Abs) or the cellular immune response generated by a primary dengue (DENV) infection on the course of a secondary zika (ZIKV) infection in vivo. Here we show that the length of time between DENV/ZIKV infections has a qualitative impact on controlling early ZIKV replication. Depletion of DENV2-specific Abs in sera confirmed that those type-specific Abs do not contribute to ZIKV control. We show that the magnitude and durability of the neutralizing antibodies (nAbs) induced by a secondary ZIKV infection is modest compared to the response induced after a secondary heterologous DENV infection. Our in vivo results are showing a complex interplay between the cellular and innate immune responses characterized by a high frequency of plasmacytoid dendritic cells (pDC) correlating with an increase in the frequency of DENV antigen specific T cells and a significant control of ZIKV replication which is time dependent. Taken together, our results suggest that early after ZIKV infection other mechanisms such as the innate and cellular immune responses may play a predominant role in controlling ZIKV replication. Regardless of the time elapsed between infections there was no evidence of in vivo antibody-dependent enhancement (ADE) of ZIKV by DENV immunity. These findings have pivotal implications while interpreting ZIKV pathogenesis in flavivirus-experimented populations, diagnostic results interpretation and vaccine designs and schedules among others.


Asunto(s)
Dengue/inmunología , Inmunidad Celular , Inmunidad Humoral , Inmunidad Innata , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/prevención & control , Virus Zika/inmunología , Animales , Células Dendríticas/inmunología , Factores Inmunológicos , Macaca mulatta , Masculino , Linfocitos T/inmunología , Factores de Tiempo
7.
Nat Commun ; 10(1): 4316, 2019 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-31541110

RESUMEN

Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood. Here we show in rhesus macaques that the time elapsed after ZIKV infection affects the immune response to DENV infection. We show that previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV. The time interval between ZIKV and subsequent DENV infection further affects the immune response. A mid-convalescent period of 10 months after ZIKV infection results in higher and more durable antibody and T cell responses to DENV infection than a short period of 2 months. In contrast, previous ZIKV infection does not affect DENV viremia or pro-inflammatory status. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.


Asunto(s)
Dengue/inmunología , Interacciones Huésped-Patógeno/inmunología , Linfocitos T/inmunología , Infección por el Virus Zika/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Línea Celular , Reacciones Cruzadas/inmunología , Citocinas/metabolismo , Virus del Dengue/inmunología , Humanos , Inmunidad , Inmunidad Celular , Macaca mulatta/inmunología , Masculino , Factores de Tiempo , Viremia , Virus Zika/inmunología
8.
Nat Commun ; 8: 15674, 2017 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-28643775

RESUMEN

Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using DENV-immune serum, it has been shown in vitro that antibody-dependent enhancement (ADE) of ZIKV infection can occur. Here we study the effects of pre-existing DENV immunity on ZIKV infection in vivo. We infect two cohorts of rhesus macaques with ZIKV; one cohort has been exposed to DENV 2.8 years earlier and a second control cohort is naïve to flaviviral infection. Our results, while confirming ADE in vitro, suggest that pre-existing DENV immunity does not result in more severe ZIKV disease. Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis.


Asunto(s)
Acrecentamiento Dependiente de Anticuerpo , Dengue/inmunología , Infección por el Virus Zika/inmunología , Virus Zika/patogenicidad , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas/inmunología , Citocinas/inmunología , Virus del Dengue , Humanos , Sueros Inmunes , Células K562 , Macaca mulatta , Masculino , Modelos Animales , Proteínas del Envoltorio Viral/inmunología
9.
Am J Trop Med Hyg ; 95(4): 852-855, 2016 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-27549636

RESUMEN

In the United States, infection with Fasciola hepatica has been identified as an emerging disease, primarily in immigrants, refugees, and travelers. The laboratory test of choice for diagnosis of fascioliasis is detection of disease specific antibodies, most commonly uses excretory-secretory antigens for detection of IgG antibodies. Recently, recombinant proteins such as F. hepatica antigen (FhSAP2) have been used to detect IgG antibodies. The glutathione S-transferase (GST)-FhSAP2 recombinant antigen was used to develop Western blot (WB) and fluorescent bead-based (Luminex) assays to detect F. hepatica total IgG and IgG4 antibodies. The sensitivity and specificity of GST-FhSAP2 total IgG and IgG4 WB were similar at 94% and 98%, respectively. For the IgG Luminex assay, the sensitivity and specificity were 94% and 97%, and for the IgG4, the values were 100% and 99%, respectively. In conclusion, the GST-FhSAP2 antigen performs well in several assay formats and can be used for clinical diagnosis.


Asunto(s)
Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Fasciola hepatica/inmunología , Fascioliasis/diagnóstico , Inmunoglobulina G/inmunología , Animales , Western Blotting , Estudios de Casos y Controles , Enfermedad Crónica , Reacciones Cruzadas/inmunología , Fascioliasis/inmunología , Técnica del Anticuerpo Fluorescente , Glutatión Transferasa , Infecciones por Uncinaria/inmunología , Humanos , Esquistosomiasis Japónica/inmunología , Sensibilidad y Especificidad , Pruebas Serológicas , Toxocariasis/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA