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2.
Science ; : eabm0829, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648302

RESUMO

The durability of immune memory after SARS-CoV-2 mRNA vaccination remains unclear. Here, we longitudinally profiled vaccine responses in SARS-CoV-2 naïve and recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. We found mRNA vaccines generated functional memory B cells that increased from 3-6 months post-vaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with pre-existing immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and variants for at least 6 months after mRNA vaccination.

3.
Cell Host Microbe ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34688376

RESUMO

The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.

4.
medRxiv ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34580675

RESUMO

Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.

5.
Nat Med ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522051

RESUMO

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.

6.
medRxiv ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34580676

RESUMO

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. In this study, through a fine-needle-aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant (KTX) recipients. We found that, unlike healthy subjects, KTX recipients presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cells, SARS-CoV-2 receptor-binding-domain-specific memory B cells and neutralizing antibodies. KTX recipients also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals, and suggest a GC-origin for certain humoral and memory B cell responses following mRNA vaccination.

7.
Clin Infect Dis ; 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34537835

RESUMO

BACKGROUND: The development of effective vaccines against COVID-19 is a global priority. CoronaVac is an inactivated SARS-CoV-2 vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 in a phase 3 clinical trial. METHODS: Volunteers randomly received two doses of CoronaVac or placebo, separated by two weeks. 434 volunteers were enrolled, 397 aged 18-59 years, and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-RBD IgG were 86.67% in the 18-59 age group and 70.37% in the ≥60 age group, two and four weeks after the second dose. A significant increase in circulating neutralizing antibodies was detected two and four weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T cell responses characterized by the secretion of IFN-γupon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γupon stimulation with SARS-CoV-2 antigens.

9.
Immunity ; 54(9): 2133-2142.e3, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34453880

RESUMO

SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , SARS-CoV-2/fisiologia , Células Th1/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização Secundária , Memória Imunológica , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Adulto Jovem
10.
Viruses ; 13(7)2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34372525

RESUMO

Zika virus (ZIKV) is a mosquito-borne Flavivirus with a positive-sense RNA genome, which are generally transmitted through the bite of an infected Aedes mosquito. ZIKV infections could be associated with neurological sequelae that, and otherwise produces similar clinical symptoms as other co-circulating pathogens. Past infection with one member of the Flavivirus genus often induces cross-reactive antibodies against other flaviruses. These attributes complicate the ability to differentially diagnose ZIKV infection from other endemic mosquito-borne viruses, making it both a public health issue as well as a diagnostic challenge. We report the results from serological analyses using arbovirus-specific peptides on 339 samples that were previously collected from 6 countries. Overall, we found that our multiplexed peptide-based ELISA was highly efficient for identifying ZIKV antibodies as early as 2 weeks post infection, and that it correlates with microneutralization, plaque reduction neutralization tests (PRNTs) and commercial tests for ZIKV in previously characterized samples. We observed that seropositivity varied by patient cohort, reflecting the sampling period in relation to the 2015-2016 ZIKV outbreak. This work evaluates the accuracy, specificity, and sensitivity of our peptide-based ELISA method for detecting ZIKV antibodies from geographically diverse regions. These findings can contribute to ongoing serological methods development and can be adapted for use in future studies.

11.
bioRxiv ; 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34462751

RESUMO

SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.

12.
Cell Host Microbe ; 29(7): 1076-1092, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34237248

RESUMO

Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified throughout the SARS-CoV2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance. We also report additional analysis of SARS-CoV-2 human CD4 and CD8 T cell epitope data compiled from these studies, identifying 1,400 different reported SARS-CoV-2 epitopes and revealing discrete immunodominant regions of the virus and epitopes that are more prevalently recognized. This remarkable breadth of epitope repertoire has implications for vaccine design, cross-reactivity, and immune escape by SARS-CoV-2 variants.


Assuntos
Imunidade Adaptativa , COVID-19/imunologia , Epitopos de Linfócito T/imunologia , SARS-CoV-2/imunologia , Antígenos Virais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Reações Cruzadas , Epitopos , Humanos , Epitopos Imunodominantes
13.
Cell Rep Med ; 2(7): 100355, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34230917

RESUMO

The emergence of SARS-CoV-2 variants with evidence of antibody escape highlight the importance of addressing whether the total CD4+ and CD8+ T cell recognition is also affected. Here, we compare SARS-CoV-2-specific CD4+ and CD8+ T cells against the B.1.1.7, B.1.351, P.1, and CAL.20C lineages in COVID-19 convalescents and in recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. The total reactivity against SARS-CoV-2 variants is similar in terms of magnitude and frequency of response, with decreases in the 10%-22% range observed in some assay/VOC combinations. A total of 7% and 3% of previously identified CD4+ and CD8+ T cell epitopes, respectively, are affected by mutations in the various VOCs. Thus, the SARS-CoV-2 variants analyzed here do not significantly disrupt the total SARS-CoV-2 T cell reactivity; however, the decreases observed highlight the importance for active monitoring of T cell reactivity in the context of SARS-CoV-2 evolution.

14.
Sci Immunol ; 6(61)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266981

RESUMO

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen/administração & dosagem , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Saccharomycetales/genética , Glicoproteína da Espícula de Coronavírus/genética , Administração por Inalação , Administração Intranasal , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Citocinas/imunologia , Humanos , Imunoglobulina G/imunologia , Pulmão/patologia , Macaca mulatta , Masculino , Ligação Proteica , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/imunologia , Carga Viral
15.
Sci Immunol ; 6(60)2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145066

RESUMO

The nutrient-sensing mammalian target of rapamycin (mTOR) is integral to cell fate decisions after T cell activation. Sustained mTORC1 activity favors the generation of terminally differentiated effector T cells instead of follicular helper and memory T cells. This is particularly pertinent for T cell responses of older adults who have sustained mTORC1 activation despite dysfunctional lysosomes. Here, we show that lysosome-deficient T cells rely on late endosomes rather than lysosomes as an mTORC1 activation platform, where mTORC1 is activated by sensing cytosolic amino acids. T cells from older adults have an increased expression of the plasma membrane leucine transporter SLC7A5 to provide a cytosolic amino acid source. Hence, SLC7A5 and VPS39 deficiency (a member of the HOPS complex promoting early to late endosome conversion) substantially reduced mTORC1 activities in T cells from older but not young individuals. Late endosomal mTORC1 is independent of the negative-feedback loop involving mTORC1-induced inactivation of the transcription factor TFEB that controls expression of lysosomal genes. The resulting sustained mTORC1 activation impaired lysosome function and prevented lysosomal degradation of PD-1 in CD4+ T cells from older adults, thereby inhibiting their proliferative responses. VPS39 silencing of human T cells improved their expansion to pertussis and to SARS-CoV-2 peptides in vitro. Furthermore, adoptive transfer of CD4+ Vps39-deficient LCMV-specific SMARTA cells improved germinal center responses, CD8+ memory T cell generation, and recall responses to infection. Thus, curtailing late endosomal mTORC1 activity is a promising strategy to enhance T cell immunity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Endossomos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , SARS-CoV-2/metabolismo , Transdução de Sinais/genética , Transferência Adotiva/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Proteínas Relacionadas à Autofagia/deficiência , Proteínas Relacionadas à Autofagia/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , COVID-19/virologia , Células Cultivadas , Feminino , Proteína Forkhead Box O1/deficiência , Proteína Forkhead Box O1/genética , Voluntários Saudáveis , Humanos , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais/imunologia , Transfecção , Proteínas de Transporte Vesicular/deficiência , Proteínas de Transporte Vesicular/genética , Adulto Jovem
16.
J Infect Dis ; 224(1): 70-80, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-33822097

RESUMO

Herein we measured CD4+ T-cell responses against common cold coronaviruses (CCC) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC-reactive T cells in SARS-CoV-2-seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T-cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T-cell reactivity was decreased in SARS-CoV-2-infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego. CD4+ T-cell responses against common cold coronaviruses (CCC) are elevated in SARS-CoV-2 seronegative high-risk health care workers (HCW) compared to COVID-19 convalescent HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses and/or cross-reactivity associated with a protective effect.


Assuntos
COVID-19/epidemiologia , COVID-19/imunologia , Pessoal de Saúde , SARS-CoV-2/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Anticorpos Antivirais , Biomarcadores , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , COVID-19/diagnóstico , COVID-19/virologia , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Imunofenotipagem , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/imunologia , Vigilância em Saúde Pública , Estudos Soroepidemiológicos , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Subpopulações de Linfócitos T/metabolismo
17.
J Virol ; 95(12)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-33789994

RESUMO

The mosquito-borne Zika virus (ZIKV) has spread rapidly into regions where dengue virus (DENV) is endemic, and flavivirus cross-reactive T cell responses have been observed repeatedly in animal models and in humans. Preexisting cellular immunity to DENV is thought to contribute to protection in subsequent ZIKV infection, but the epitope targets of cross-reactive T cell responses have not been comprehensively identified. Using human blood samples from the regions of Nicaragua and Sri Lanka where DENV is endemic that were collected before the global spread of ZIKV in 2016, we employed an in vitro expansion strategy to map ZIKV T cell epitopes in ZIKV-unexposed, DENV-seropositive donors. We identified 93 epitopes across the ZIKV proteome, and we observed patterns of immunodominance that were dependent on antigen size and sequence identity to DENV. We confirmed the immunogenicity of these epitopes through a computational HLA binding analysis, and we showed that cross-reactive T cells specifically recognize ZIKV peptides homologous to DENV sequences. We also found that these CD4 responses were derived from the memory T cell compartment. These data have implications for understanding the dynamics of flavivirus-specific T cell immunity in areas of endemicity.IMPORTANCE Multiple flaviviruses, including Zika virus (ZIKV) and the four serotypes of dengue virus (DENV), are prevalent in the same large tropical and equatorial areas, which are inhabited by hundreds of millions of people. The interplay of DENV and ZIKV infection is especially relevant, as these two viruses are endemic in largely overlapping regions, have significant sequence similarity, and share the same arthropod vector. Here, we define the targets of preexisting immunity to ZIKV in unexposed subjects in areas where dengue is endemic. We demonstrate that preexisting immunity to DENV could shape ZIKV-specific responses, and DENV-ZIKV cross-reactive T cell populations can be expanded by stimulation with ZIKV peptides. The issue of potential ZIKV and DENV cross-reactivity is of relevance for understanding patterns of natural immunity, as well as for the development of diagnostic tests and vaccines.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Memória Imunológica , Linfócitos T/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Adulto , Antígenos Virais/química , Antígenos Virais/imunologia , Reações Cruzadas , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/imunologia , Epitopos de Linfócito T/imunologia , Antígenos HLA/metabolismo , Humanos , Peptídeos/imunologia , Proteínas Virais/química , Proteínas Virais/imunologia
18.
Front Immunol ; 12: 636768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777028

RESUMO

Understanding the causes of the diverse outcome of COVID-19 pandemic in different geographical locations is important for the worldwide vaccine implementation and pandemic control responses. We analyzed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to 5 months from the recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, we identified SARS-CoV-2 cross-reactive CD4+ T cells in around 66% of the unexposed individuals. Moreover, we found detectable immune memory in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity; CD4+ T cells and B cells, with a minimal contribution from CD8+ T cells. Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of the SARS-CoV-2. This study provides the evidence of both high magnitude pre-existing and persistent immune memory in Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, our work has implication for the development and implementation of vaccines against COVID-19.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Memória Imunológica , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Linfócitos B/virologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Celular , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
19.
bioRxiv ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33688655

RESUMO

The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.

20.
medRxiv ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33655267

RESUMO

Understanding the causes of the diverse outcome of COVID-19 pandemic in different geographical locations is important for the worldwide vaccine implementation and pandemic control responses. We analyzed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to 5 months from the recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, we identified SARS-CoV-2 cross-reactive CD4 + T cells in around 66% of the unexposed individuals. Moreover, we found detectable immune memory in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity; CD4 + T cells and B cells, with a minimal contribution from CD8 + T cells. Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of the SARS-CoV-2. This study provides the evidence of both high magnitude pre-existing and persistent immune memory in Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, our work has implication for the development and implementation of vaccines against COVID-19.

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