RAFAEL RIBEIRO ALMEIDA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- T Cells Target APOBEC3 Proteins in Human Immunodeficiency Virus Type 1-Infected Humans and Simian Immunodeficiency Virus-Infected Indian Rhesus Macaques(2013) CHAMPIAT, Stephane; GARRISON, Keith E.; RAPOSO, Rui Andre Saraiva; BURWITZ, Benjamin J.; REED, Jason; TANDON, Ravi; YORK, Vanessa A.; NEWMAN, Laura P.; NIMITYONGSKUL, Francesca A.; WILSON, Nancy A.; ALMEIDA, Rafael R.; MARTIN, Jeffrey N.; DEEKS, Steven G.; ROSENBERG, Michael G.; WIZNIA, Andrew A.; SPOTTS, Gerald E.; PILCHER, Christopher D.; HECHT, Fredrick M.; OSTROWSKI, Mario A.; SACHA, Jonah B.; NIXON, Douglas F.APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger antiretroviral immune response.
- Recurrence of COVID-19 associated with reduced T-cell responses in a monozygotic twin pair(2022) V, Mateus de Castro; SANTOS, Keity S.; APOSTOLICO, Juliana S.; FERNANDES, Edgar R.; ALMEIDA, Rafael R.; LEVIN, Gabriel; MAGAWA, Jhosiene Y.; NUNES, Joao Paulo S.; BRUNI, Mirian; YAMAMOTO, Marcio M.; LIMA, Ariane C.; SILVA, Monize V. R.; MATOS, Larissa R. B.; CORIA, Vivian R.; CASTELLI, Erick C.; SCLIAR, Marilia O.; KURAMOTO, Andreia; BRUNO, Fernanda R.; JACINTHO, Lucas C.; NUNES, Kelly; WANG, Jaqueline Y. T.; COELHO, Veronica P.; NETO, Miguel Mitne; MACIEL, Rui M. B.; NASLAVSKY, Michel S.; PASSOS-BUENO, Maria Rita; BOSCARDIN, Silvia B.; ROSA, Daniela S.; KALIL, Jorge; ZATZ, Mayana; CUNHA-NETO, EdecioRecurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFN gamma) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19.
- Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms(2022) BROCHET, Pauline; IANNI, Barbara; NUNES, Joao P. S.; FRADE, Amanda F.; TEIXEIRA, Priscila C.; MADY, Charles; FERREIRA, Ludmila R. P.; KURAMOTO, Andreia; PISSETTI, Cristina W.; SABA, Bruno; CANDIDO, Darlan D. S.; DIAS, Fabricio; SAMPAIO, Marcelo; MARIN-NETO, Jose A.; FRAGATA, Abilio; ZANIRATTO, Ricardo C. F.; SIQUEIRA, Sergio; PEIXOTO, Giselle D. L.; RIGAUD, Vagner O. C.; BUCK, Paula; ALMEIDA, Rafael R.; LIN-WANG, Hui Tzu; SCHMIDT, Andre; MARTINELLI, Martino; HIRATA, Mario H.; DONADI, Eduardo; JUNIOR, Virmondes Rodrigues; PEREIRA, Alexandre C.; KALIL, Jorge; SPINELLI, Lionel; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) >= 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.
- Bicistronic DNA Vaccines Simultaneously Encoding HIV, HSV and HPV Antigens Promote CD8(+) T Cell Responses and Protective Immunity(2013) SANTANA, Vinicius C.; DINIZ, Mariana O.; CARIRI, Francisco A. M. O.; VENTURA, Armando M.; CUNHA-NETO, Edecio; ALMEIDA, Rafael R.; CAMPOS, Marco A.; LIMA, Graciela K.; FERREIRA, Luis C. S.Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8(+) T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8(+) T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.
- Reduced T Cell and Antibody Responses to Inactivated Coronavirus Vaccine Among Individuals Above 55 Years Old(2022) MEDEIROS, Giuliana X.; SASAHARA, Greyce Luri; MAGAWA, Jhosiene Y.; NUNES, Joao Paulo S.; BRUNO, Fernanda R.; KURAMOTO, Andreia C.; ALMEIDA, Rafael R.; FERREIRA, Marcelo A.; SCAGION, Guilherme P.; CANDIDO, Erika D.; LEAL, Fabyano B.; OLIVEIRA, Danielle B. L.; DURIGON, Edison L.; SILVA JR., Roberto Carlos V.; ROSA, Daniela S.; BOSCARDIN, Silvia B.; COELHO, Veronica; KALIL, Jorge; SANTOS, Keity S.; CUNHA-NETO, EdecioCoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals. The frequency among vaccinated individuals, of whom 96% displayed T cell and/or antibody responses to SARS-CoV-2, is comparable to 98.5% responses of convalescent individuals. We observed that among vaccinated individuals, men and individuals 55 years or older developed significantly lower anti-RBD, anti-NP and neutralization titers against the Wuhan strain and antigen-induced IL-2 production by T cells. Neutralizing antibody responses for Gamma variant were even lower than for the Wuhan strain. Even though some studies indicated CoronaVac helped reduce mortality among elderly people, considering the appearance of novel variants of concern, CoronaVac vaccinated individuals above 55 years old are likely to benefit from a heterologous third dose/booster vaccine to increase immune response and likely protection.