RESUMEN
BBV152 is a whole-virion inactivated vaccine based on the Asp614Gly variant. BBV152 is the first alum-imidazoquinolin-adjuvanted vaccine authorized for use in large populations. Here we characterized the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months post vaccination. We report that the magnitude of vaccine-induced spike and nucleoprotein antibodies was comparable with that produced after infection. Receptor binding domain-specific antibodies declined against variants in the order of Alpha (B.1.1.7; 3-fold), Delta (B.1.617.2; 7-fold) and Beta (B.1.351; 10-fold). However, pseudovirus neutralizing antibodies declined up to 2-fold against the Delta followed by the Beta variant (1.7-fold). Vaccine-induced memory B cells were also affected by the Delta and Beta variants. The SARS-CoV-2-specific multicytokine-expressing CD4+ T cells were found in ~85% of vaccinated individuals. Only a ~1.3-fold reduction in efficacy was observed in CD4+ T cells against the Beta variant. We found that antigen-specific CD4+ T cells were present in the central memory compartment and persisted for at least up to 6 months post vaccination. Vaccine-induced CD8+ T cells were detected in ~50% of individuals. Importantly, the vaccine was capable of inducing follicular T helper cells that exhibited B-cell help potential. These findings show that inactivated vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern that persists for at least 6 months after vaccination.
Asunto(s)
COVID-19 , Vacunas Virales , Linfocitos T CD8-positivos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Memoria Inmunológica , SARS-CoV-2 , Vacunas de Productos Inactivados , ViriónRESUMEN
The B cell "help" function of CD4+ T cells is an important mechanism of adaptive immunity. Here, we describe improved antigen-specific T-B cocultures for quantitative measurement of T cell-dependent B cell responses, with as few as â¼90 T cells. Utilizing M. tuberculosis (Mtb), we show that early priming and activation of CD4+ T cells is important for productive interaction between T and B cells and that similar effects are achieved by supplementing cocultures with monocytes. We find that monocytes promote survivability of B cells via BAFF and stem cell growth factor (SCGF)/C-type lectin domain family 11 member A (CLEC11A), but this alone does not fully recapitulate the effects of monocyte supplementation. Importantly, we demonstrate improved activation and immunological output of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory CD4+ T-B cell cocultures with the inclusion of monocytes. This method may therefore provide a more sensitive assay to evaluate the B cell help quality of memory CD4+ T cells, for example, after vaccination or natural infection.
Asunto(s)
Linfocitos B , Linfocitos T CD4-Positivos , COVID-19 , Memoria Inmunológica , Humanos , Linfocitos T CD4-Positivos/inmunología , COVID-19/inmunología , Mycobacterium tuberculosis , SARS-CoV-2 , Linfocitos B/inmunología , InmunoensayoRESUMEN
A comprehensive understanding of the human immune response to virus infection is imperative for developing effective therapies, antivirals, and vaccines. Dendritic cells (DCs) are among the first cells to encounter the virus and are also key antigen-presenting cells that link the innate and adaptive immune system. In this study, we focus on the human immune response to the mosquito-borne Japanese encephalitis virus (JEV), which is the leading cause of virus-induced encephalitis in south-east Asia and has the potential to become a global pathogen. We describe the gene regulatory circuit of JEV infection in human monocyte-derived DCs (moDCs) along with its functional validation. We observe that JEV can productively infect human moDCs leading to robust transcriptional activation of the interferon and NF-κB-mediated antiviral and inflammatory pathways. This is accompanied with DC maturation and release of pro-inflammatory cytokines and chemokines TNFα, IL-6, IL-8, IL-12, MCP-1. and RANTES. JEV-infected moDCs activated T-regulatory cells (Tregs) in allogenic mixed lymphocyte reactions (MLR) as seen by upregulated FOXP3 mRNA expression, suggestive of a host response to reduce virus-induced immunopathology. The virus also downregulated transcripts involved in Peroxisome Proliferator Activated Receptor (PPAR) signalling and fatty acid metabolism pathways suggesting that changes in cellular metabolism play a crucial role in driving the DC maturation and antiviral responses. Collectively, our data describe and corroborate the human DC transcriptional network that is engaged upon JEV sensing.
Asunto(s)
Células Dendríticas/inmunología , Virus de la Encefalitis Japonesa (Especie)/fisiología , Encefalitis Japonesa/inmunología , Inflamación/inmunología , Monocitos/inmunología , Linfocitos T Reguladores/inmunología , Antivirales , Células Cultivadas , Factores de Transcripción Forkhead/metabolismo , Redes Reguladoras de Genes , Humanos , Inmunidad , Mediadores de Inflamación , Interferón gamma/genética , Interferón gamma/metabolismo , Metabolismo de los Lípidos , FN-kappa B/genética , FN-kappa B/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismoRESUMEN
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.
Asunto(s)
Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , COVID-19/inmunología , Memoria Inmunológica , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Linfocitos B/virología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/virología , Estudios de Casos y Controles , Femenino , Humanos , Inmunidad Celular , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
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.