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BACKGROUND: Human adenoviruses (HAdVs) are extensively used as vectors for vaccines development and cancer therapy. People who already have antibodies against HAdVs, on the other hand, would have an impact on the preventative or therapeutic effect. This review focuses primarily on the prevalence of pre-existing antibodies against HAdVs in distinct geographical populations. SUMMARY: After screening, 64 studies from 31 countries between 1962 and 2021 were selected, totaling 39,427 samples. The total prevalence of preexisting antibodies to HAdVs varied by country or location, ranging from 2.00 to 95.70%. Southeast Asia had the highest prevalence (54.57%) while Europe had the lowest (18.17%). The prevalence in practically all developing nations was higher than in developed nations. Adults have a greater frequency than children and newborns in most nations. The primary HAdV antibody types varied by country. Adults in China, the USA, the United Kingdom, and Belgium had the lowest prevalence of preexisting antibodies against HAdV55, HAdV37, HAdV8, and HAdV36, respectively. Children in the USA, China, the United Kingdom, and Japan had the lowest rates of HAdV48, HAdV11, HAdV8, and HAdV40. The frequency of antibodies differed significantly between military and civilian groups. KEY MESSAGES: Preexisting antibodies against various types of HAdVs differed greatly throughout worldwide populations. Future development of HAdV-vector vaccines and medicines should focus on preexisting antibodies in target groups rather than a "one-size-fits-all" strategy. It might be advantageous in selecting HAdV vectors for studying the prevalence of preexisting antibodies against HAdVs in different locations and people throughout the world.
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Infecciones por Adenovirus Humanos , Adenovirus Humanos , Anticuerpos Antivirales , Humanos , Adenovirus Humanos/inmunología , Anticuerpos Antivirales/sangre , Infecciones por Adenovirus Humanos/epidemiología , Infecciones por Adenovirus Humanos/inmunología , Prevalencia , Salud Global , Niño , Adulto , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: Factors influencing susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain to be resolved. Using data from the Swiss HIV Cohort Study on 6270 people with human immunodeficiency virus (HIV) and serologic assessment for SARS-CoV-2 and circulating human coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection. METHODS: We analyzed SARS-CoV-2 polymerase chain reaction test results, COVID-19-related hospitalizations, and deaths reported to the Swiss HIV Cohort Study between 1 January 2020 and 31 December 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in prepandemic (2019) and pandemic (2020) biobanked plasma samples and compared with findings in HIV-negative individuals. We applied logistic regression, conditional logistic regression, and bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and antibody responses to SARS-CoV-2 in people with HIV. RESULTS: No HIV-1-related factors were associated with SARS-CoV-2 acquisition. High prepandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses on infection. We observed a robust protective effect of smoking on SARS-CoV-2 infection risk (adjusted odds ratio, 0.46 [95% confidence interval, .38-.56]; P < .001), which occurred even in previous smokers and was highest for heavy smokers. CONCLUSIONS: Our findings of 2 independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2.
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Anticuerpos Antivirales , COVID-19 , Infecciones por VIH , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Masculino , Femenino , Persona de Mediana Edad , Suiza/epidemiología , SARS-CoV-2/inmunología , Estudios de Cohortes , Adulto , Anticuerpos Antivirales/sangre , Susceptibilidad a Enfermedades , Factores de Riesgo , AncianoRESUMEN
An oncolytic virus is a promising strategy for glioblastoma (GBM) therapy. However, there are still some challenges such as the blood-brain barrier (BBB) and preexisting immunity for targeted treatment of GBM with an oncolytic virus. In this study, two kinds of cell membrane-coated oncolytic adenoviruses (NCM-Ad and GCM-Ad) were prepared using neural stem cells (NSCs) and GBM cells as sources of membranes, respectively, and were shown to improve the targeted infectivity on GBM cells and avoid the immune clearance of preexisting neutralizing antibodies in vitro and in vivo. Specifically, NCM-Ad showed a strong ability to cross the BBB and target tumor cells in vivo. To improve the cytotoxicity to GBM, a capsid dual-modified oncolytic adenovirus (A4/k37) was also encapsulated, and NCM-A4/k37 showed outstanding tumor targeting and inhibition capacity in an orthotopic xenograft tumor model of GBM upon intravenous administration. This study provides a promising oncolytic virus-based targeted therapeutic strategy for glioma.
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Neoplasias Encefálicas , Glioblastoma , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Glioblastoma/terapia , Glioblastoma/patología , Adenoviridae/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Virus Oncolíticos/genética , Membrana Celular/metabolismoRESUMEN
The widespread preexisting immunity against virus-like particles (VLPs) seriously limits the applications of VLPs as vaccine vectors. Enabling technology for exogenous antigen display should not only ensure the assembly ability of VLPs and site-specific modification, but also consider the effect of preexisting immunity on the behavior of VLPs in vivo. Here, combining genetic code expansion technique and synthetic biology strategy, a site-specific modification method for hepatitis B core (HBc) VLPs via incorporating azido-phenylalanine into the desired positions is described. Through modification position screening, it is found that HBc VLPs incorporated with azido-phenylalanine at the main immune region can effectively assemble and rapidly conjugate with the dibenzocycolctyne-modified tumor-associated antigens, mucin-1 (MUC1). The site-specific modification of HBc VLPs not only improves the immunogenicity of MUC1 antigens but also shields the immunogenicity of HBc VLPs themselves, thereby activating a strong and persistent anti-MUC1 immune response even in the presence of preexisting anti-HBc immunity, which results in the efficient tumor elimination in a lung metastatic mouse model. Together, these results demonstrate the site-specific modification strategy enabled HBc VLPs behave as a potent antitumor vaccine and this strategy to manipulate immunogenicity of VLPs may be suitable for other VLP-based vaccine vectors.
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Virus de la Hepatitis B , Vacunas de Partículas Similares a Virus , Animales , Ratones , Virus de la Hepatitis B/genética , Vacunas de Partículas Similares a Virus/genética , Antígenos de Neoplasias , Ratones Endogámicos BALB CRESUMEN
Oncolytic viruses (OVs) represent a highly promising treatment strategy for a wide range of cancers, by mediating both the direct killing of tumor cells as well as mobilization of antitumor immune responses. As many OVs circulate in the human population, preexisting OV-specific immune responses are prevalent. Indeed, neutralizing antibodies (NAbs) are abundantly present in the human population for commonly used OVs, such as Adenovirus type 5 (Ad5), Herpes Simplex Virus-1 (HSV-1), Vaccinia virus, Measles virus, and Reovirus. This review discusses (pre)clinical evidence regarding the effect of preexisting immunity against OVs on two distinct aspects of OV therapy; OV infection and spread, as well as the immune response induced upon OV therapy. Combined, this review provides evidence that consideration of preexisting immunity is crucial in realizing the full potential of the highly promising therapeutic implementation of OVs. Future investigation of current gaps in knowledge highlighted in this review should yield a more complete understanding of this topic, ultimately allowing for better and more personalized OV therapies.
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Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Neoplasias/terapia , Anticuerpos Neutralizantes/uso terapéuticoRESUMEN
Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5-host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus-adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.
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An adenoviral (AdV)-based vector system is a promising platform for vaccine development and gene therapy applications. Administration of an AdV vector elicits robust innate immunity, leading to the development of humoral and cellular immune responses against the vector and the transgene antigen, if applicable. The use of high doses (1011-1013 virus particles) of an AdV vector, especially for gene therapy applications, could lead to vector toxicity due to excessive levels of innate immune responses, vector interactions with blood factors, or high levels of vector transduction in the liver and spleen. Additionally, the high prevalence of AdV infections in humans or the first inoculation with the AdV vector result in the development of vector-specific immune responses, popularly known as preexisting vector immunity. It significantly reduces the vector efficiency following the use of an AdV vector that is prone to preexisting vector immunity. Several approaches have been developed to overcome this problem. The utilization of rare human AdV types or nonhuman AdVs is the primary strategy to evade preexisting vector immunity. The use of heterologous viral vectors, capsid modification, and vector encapsulation are alternative methods to evade vector immunity. The vectors can be optimized for clinical applications with comprehensive knowledge of AdV vector immunity, toxicity, and circumvention strategies.
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Infecciones por Adenoviridae , Adenoviridae , Humanos , Adenoviridae/genética , Terapia Genética , Vacunación , Transgenes , Vectores Genéticos/genética , Inmunidad InnataRESUMEN
Although the coronavirus disease 2019 (COVID-19) epidemic is still ongoing, vaccination rates are rising slowly and related treatments and drugs are being developed. At the same time, there is increasing evidence of preexisting immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, mainly consisting of preexisting antibodies and immune cells (including T cells and B cells). The presence of these antibodies is mainly due to the seasonal prevalence of four common coronavirus types, especially OC43 and HKU1. The accumulated relevant evidence has suggested that the target of antibodies is mainly the S2 subunit of S protein, followed by evolutionary conservative regions such as the nucleocapsid (N) protein. Additionally, preexisting memory T and B cells are also present in the population. Preexisting antibodies can help the body protect against SARS-CoV-2 infection, reduce the severity of COVID-19, and rapidly increase the immune response post-infection. These multiple effects can directly affect disease progression and even the likelihood of death in certain individuals. Besides the positive effects, preexisting immunity may also have negative consequences, such as antibody-dependent enhancement (ADE) and original antigenic sin (OAS), the prevalence of which needs to be further established. In the future, more research should be focused on evaluating the role of preexisting immunity in COVID-19 outcomes, adopting appropriate policies and strategies for fighting the pandemic, and vaccine development that considers preexisting immunity.
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COVID-19 , Pandemias , Humanos , SARS-CoV-2 , Estaciones del Año , Glicoproteína de la Espiga del CoronavirusRESUMEN
This secondary analysis of the phase 3 ENSEMBLE trial (NCT04505722) assessed the impact of preexisting humoral immunity to adenovirus 26 (Ad26) on the immunogenicity of Ad26.COV2.S-elicited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody levels in 380 participants in Brazil, South Africa, and the United States. Among those vaccinated in Brazil and South Africa, 31% and 66%, respectively, had prevaccination serum-neutralizing activity against Ad26, with little preexisting immunity detected in the United States. Vaccine recipients in each country had similar postvaccination spike (S) protein-binding antibody levels, indicating that baseline immunity to Ad26 has no clear impact on vaccine-induced immune responses.
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Infecciones por Adenoviridae , COVID-19 , Ad26COVS1 , Adenoviridae , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Vectores Genéticos , Humanos , Inmunidad Celular , Inmunidad Humoral , Inmunogenicidad Vacunal , SARS-CoV-2RESUMEN
Background: The comprehensive impacts of diverse breathing air volumes and preexisting immunity on the host susceptibility to and transmission of COVID-19 at various pandemic stages have not been investigated. Methods: We classified the US weekly COVID-19 data into 0-4, 5-11, 12-17, 18-64, and 65+ age groups and applied the odds ratio (OR) of incidence between one age group and the 18-64 age group to delineate the transmissibility change. Results: The changes of incidence ORs between May, 2020 and November, 2021 were 0.22-0.66 (0-4 years), 0.20-1.34 (5-11 years), 0.39-1.04 (12-17 years), and 0.82-0.73 (65+ years). The changes could be explained by age-specific preexisting immunity including previous infection and vaccination, as well as volumes of breathing air. At the early pandemic, the ratio that 0-4-year children exhaled one-fifth of air and discharge a similar ratio of viruses was closely associated with incidence OR between two age groups. While, after a rollout of pandemic and vaccination, the much less increased preexisting immunity in children resulted in rapidly increased OR of incidence. The ARIMA model predicted the largest increase of relative transmissibility in 6 coming months in 5-11-year children. Conclusions: The volume of breathing air may be a notable factor contributing to the infectivity of COVID-19 among different age groups of patients. This factor and the varied preexisting greatly shape the transmission of COVID-19 at different periods of pandemic among different age groups of people.
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COVID-19 , Factores de Edad , COVID-19/epidemiología , Niño , Gobierno , Humanos , Pandemias , VacunaciónAsunto(s)
COVID-19/inmunología , Infecciones por Coronaviridae/prevención & control , Proteínas de la Envoltura de Coronavirus/inmunología , Protección Cruzada , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Antivirales/biosíntesis , Antígenos Virales/biosíntesis , COVID-19/epidemiología , COVID-19/virología , Resfriado Común/epidemiología , Resfriado Común/inmunología , Resfriado Común/virología , Coronaviridae/inmunología , Infecciones por Coronaviridae/epidemiología , Infecciones por Coronaviridae/inmunología , Infecciones por Coronaviridae/virología , Proteínas de la Envoltura de Coronavirus/genética , Proteínas M de Coronavirus/genética , Proteínas M de Coronavirus/inmunología , Proteínas de la Nucleocápside de Coronavirus/genética , Proteínas de la Nucleocápside de Coronavirus/inmunología , Reacciones Cruzadas , Enfermedades Endémicas , Humanos , Aprendizaje Automático/estadística & datos numéricos , Fosfoproteínas/genética , Fosfoproteínas/inmunología , SARS-CoV-2/patogenicidad , Homología de Secuencia de Aminoácido , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
Although the coronavirus disease 2019 (COVID-19) epidemic is still ongoing, vaccination rates are rising slowly and related treatments and drugs are being developed. At the same time, there is increasing evidence of preexisting immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, mainly consisting of preexisting antibodies and immune cells (including T cells and B cells). The presence of these antibodies is mainly due to the seasonal prevalence of four common coronavirus types, especially OC43 and HKU1. The accumulated relevant evidence has suggested that the target of antibodies is mainly the S2 subunit of S protein, followed by evolutionary conservative regions such as the nucleocapsid (N) protein. Additionally, preexisting memory T and B cells are also present in the population. Preexisting antibodies can help the body protect against SARS-CoV-2 infection, reduce the severity of COVID-19, and rapidly increase the immune response post-infection. These multiple effects can directly affect disease progression and even the likelihood of death in certain individuals. Besides the positive effects, preexisting immunity may also have negative consequences, such as antibody-dependent enhancement (ADE) and original antigenic sin (OAS), the prevalence of which needs to be further established. In the future, more research should be focused on evaluating the role of preexisting immunity in COVID-19 outcomes, adopting appropriate policies and strategies for fighting the pandemic, and vaccine development that considers preexisting immunity.
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Humanos , COVID-19 , Pandemias , SARS-CoV-2 , Estaciones del Año , Glicoproteína de la Espiga del CoronavirusRESUMEN
We tested the concept that host preexisting influenza A virus immunity can be redirected to inhibit tumor growth and metastasis through systemic administration of influenza A virus-related peptides to targeted tumors. Mice infected with influenza A virus strain A/Puerto Rico/8/34 (PR8) were used as a model of a host with preexisting viral immunity. The extent to which preexisting influenza A immunity in PR8-immunized mice can be redirected to inhibit tumor growth and metastasis was first examined by ectopic expression of influenza A nucleoprotein (NP) and hemagglutinin (HA) in syngeneic mammary tumor cells via lentiviral transduction. Then, the feasibility of implementing this strategy using a systemic therapy approach was assessed by systemic delivery of major histocompatibility complex class I (MHC-I)-compatible peptides to targeted mammary tumors overexpressing human epidermal growth factor receptor-2 (HER2) in mice using a novel HER2-targeting single-lipid nanoparticle (SLNP). Our results show that preexisting influenza A immunity in PR8-immunized mice could be quickly redirected to syngeneic tumors expressing influenza A NP and HA, leading to strong inhibition of tumor growth and metastasis and improvement of survival compared to the findings in antigen-naïve control mice. MHC-I-compatible peptides could be delivered to targeted mammary tumors in mice using the HER2-targeting SLNP for antigen presentation, which subsequently redirected preexisting influenza A immunity to the tumors to exert antitumor activities. In conclusion, preexisting influenza A immunity can be repurposed for cancer immunotherapy through systemic delivery of influenza A-related peptides to targeted tumors. Further development of the strategy for clinical translation is warranted.
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Virus de la Influenza A , Gripe Humana , Neoplasias , Infecciones por Orthomyxoviridae , Animales , Anticuerpos Antivirales , Humanos , Inmunoterapia , Gripe Humana/prevención & control , Liposomas , Ratones , Ratones Endogámicos BALB C , Nanopartículas , Neoplasias/terapia , Infecciones por Orthomyxoviridae/prevención & control , PéptidosRESUMEN
Opioid use disorder (OUD) is a serious health problem that has dramatically increased over the last decade. Although current therapies for the management of OUD can be effective, they have limitations. The complementary strategy to combat the opioid crisis is the development of a conjugate vaccine to generate high affinity antibodies in order to neutralize opioids in circulation before reaching the brain. The components of an opioid vaccine include an opioid hapten (6-AmHap) that is conjugated to a carrier protein (tetanus toxoid) with the addition of adjuvants (Army Liposome Formulation adsorbed to aluminum hydroxide-ALFA). There is no consensus in the literature as to whether preexisting immunity to the carrier protein may impact the immunogenicity of the conjugate vaccine by inducing an enhanced or suppressed immune response to the hapten. Here, we investigated whether pre-exposure to tetanus toxoid would affect the immunogenicity and efficacy of the heroin vaccine, TT-6-AmHap. Mice were primed with diphtheria, tetanus, and acellular pertussis (DTaP) vaccine at weeks -4 and -2, then immunized with TT-6-AmHap vaccine at weeks 0, 3, and 6. Using ELISA and behavioral assays, we found that preexisting immunity to tetanus toxoid had no influence on the immunogenicity and efficacy of the TT-6-AmHap vaccine.
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Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.
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Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Linfocitos B/inmunología , COVID-19/inmunología , Interacciones Huésped-Patógeno/inmunología , Epítopos Inmunodominantes/inmunología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/inmunología , Formación de Anticuerpos/genética , Linfocitos B/metabolismo , Biología Computacional/métodos , Reacciones Cruzadas/inmunología , Mapeo Epitopo , Femenino , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno/genética , Humanos , Epítopos Inmunodominantes/genética , Memoria Inmunológica , Masculino , Pruebas de Neutralización , Análisis de la Célula Individual/métodos , Glicoproteína de la Espiga del Coronavirus/inmunología , TranscriptomaRESUMEN
Due to its richness in antigen presenting cells, e.g., dendritic cells (DC), the skin has been identified as a promising route for immunotherapy and vaccination. Several years ago, a skin delivery system was developed based on epicutaneous patches allowing the administration of antigen through intact skin. Using mouse models, we have shown that epicutaneous allergen application leads to a rapid uptake and transport of allergen-positive cells to skin-draining lymph nodes (LN). This occurred primarily in animals previously sensitized to the same allergen. In that context, we sought to better understand the role of the specific preexisting immunity in allergen capture by skin DC and their subsequent migration to LN. Specifically, we investigated the role of humoral immunity induced by sensitization and the involvement of IgG Fc receptors (FcγR). Epicutaneous patches containing fluorescently-labeled ovalbumin (OVA) were applied to naïve mice that had previously received either sera or purified IgG isolated from OVA-sensitized mice. To investigate the involvement of FcγR, animals received 2.4G2 (anti-FcγRII/RIII) blocking antibody, 24 hours before patch application. Mice that received sera or purified IgG originating from OVA-sensitized mice showed an increase in the quantity of OVA-positive DC in skin and LN. Moreover, the blockade of FcγR reduced the number of OVA-positive DC in LN to a level similar to that observed in naïve animals. Overall, these results demonstrate that preexisting specific-IgG antibodies are involved in allergen capture by skin DC following EPIT through the involvement of antigen-specific IgG-FcγR.
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Alérgenos/inmunología , Movimiento Celular/inmunología , Inmunidad Humoral , Células de Langerhans/inmunología , Ganglios Linfáticos/inmunología , Alérgenos/administración & dosificación , Animales , Biomarcadores , Modelos Animales de Enfermedad , Hipersensibilidad/inmunología , Hipersensibilidad/terapia , Inmunización , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Inmunofenotipificación , Células de Langerhans/metabolismo , Ganglios Linfáticos/metabolismo , Ratones , Receptores Fc/metabolismoRESUMEN
Annual flu led by influenza viruses is contemplated to be one of the foremost global health challenges due to its rapid spread leading to the life-threatening epidemic or pandemic. An enormous number of people die due to flu and its associated intricacies every year. Annual vaccination is considered to be the gold standard strategy to protect the individual from acquiring infection and further decimation, although recent estimates suggest that overall flu vaccine effectiveness was within 19% to 53% in last five years. A significant weakness of current vaccination is its inability to protect an individual from different or mutant flu strain. Host immune system performs a vital role during natural infection or after vaccination leading to influenza-specific immunities. Previous imprints of common flu or vaccination may alter the outcomes of the current vaccination. Current flu vaccine regime does not consider the host immune status before vaccination. Irrespective of the previous influenza exposure history or prior flu vaccination, individual get flu vaccination based on WHO recommendation with selected strains which may be the reason why induction of broad immunities does not transpire with their testimonial. Over the last few decades, scientific research had identified the role of preexisting immunities on vaccination or natural infection outcome. In this review, we are proposing the concept of personalized flu vaccines depending on individual immune status. We will also discuss why individual was unable to induce broader immunities to protect itself from diverse influenza viruses and how we can accomplish that goal with the current findings.
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Variación Genética/inmunología , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Vacunación/estadística & datos numéricos , Variación Genética/genética , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/virología , Inmunidad/inmunología , Virus de la Influenza A/genética , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pandemias/prevención & control , Medicina de Precisión/métodos , Vacunación/métodosRESUMEN
Adenovirus (AdV)-based vectors are popular experimental vaccine vectors, but despite their ability to induce strong immune responses, their application is impeded by widespread preexisting immunity against many AdV types that can impair or even abrogate the induction of transgene-specific immune responses. Therefore, the development of vectors based on AdV types with a low seroprevalence is important for effective AdV-based immunization in humans. We investigated the immunization efficacy of vectors based on AdV type 48 (Ad48) and Ad50 in the ovalbumin (ova) model as well as the Friend retrovirus (FV) model, which allows testing of the protective effect of vaccine-induced immunity. Using ova-encoding vectors, we found a significantly lower induction of ova-specific CD8+ T cells and antibody responses by Ad48- and Ad50-based vectors than by Ad5-based vectors. Similarly, we found a reduced induction of FV-specific CD8+ T cell responses in Ad48- and Ad50.Leader-Gag-immunized mice compared with that in Ad5-immunized mice; however, some of those mice were able to control the FV infection, and protection correlated with the level of neutralizing antibodies 10 days after FV challenge. Analyses of the AdV-specific antibodies and CD8+ T cells induced by the individual AdV types revealed a high level of cross-reactivity, and the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Our results show that the immunity induced by Ad48- and Ad50-based vectors is reduced compared to that induced by Ad5 and is sufficient to control FV infection in only some of the immunized mice. A high level of cross-reactivity suggests that AdV preimmunity must be considered even when applying rare AdV-based vectors.IMPORTANCE AdV-based vectors are important tools for the development of vaccines against a wide range of pathogens. While AdV vectors are generally considered safe and highly effective, their application can be severely impaired by preexisting immunity due to the widespread seroprevalence of some AdV types. The characterization of different AdV types with regard to immunogenicity and efficacy in challenge models is of great importance for the development of improved AdV-based vectors that allow for efficient immunization despite anti-AdV immunity. We show that the immunity induced by an Ad48-based vector is inferior to that induced by an Ad5-based vector but can still mediate the control of an FV infection in highly FV-susceptible mice. However, the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Importantly, we found cross-reactivity of both the humoral and cellular immune responses raised by the individual AdV types, suggesting that switching to a different AdV type may not be sufficient to circumvent preexisting anti-AdV immunity.
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Infecciones por Adenoviridae/inmunología , Adenoviridae/clasificación , Adenoviridae/inmunología , Vacunas contra el Adenovirus/administración & dosificación , Anticuerpos Antivirales/inmunología , Inmunidad Celular/inmunología , Infecciones por Retroviridae/inmunología , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/virología , Vacunas contra el Adenovirus/inmunología , Animales , Antígenos Virales/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Femenino , Vectores Genéticos/administración & dosificación , Humanos , Inmunización , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Retroviridae/inmunología , Infecciones por Retroviridae/prevención & control , Infecciones por Retroviridae/virologíaRESUMEN
Influenza A annually infects 5-10% of the world's human population resulting in one million deaths. Influenza causes annual epidemics and reinfects previously exposed individuals because of antigenic drift in the glycoprotein hemagglutinin. Due to antigenic drift, the immune system is simultaneously exposed to novel and conserved parts of the influenza virus via vaccination and/or infection throughout life. Preexisting immunity has long been known to augment subsequent hemagglutination inhibitory antibody (hAb) responses. However, the preexisting immunological contributors that influence hAb responses are not understood. Therefore, we adapted and developed sequential infection and immunization mouse models using drifted influenza strains to show that MHC Class II haplotype and T-cell reactivity influences subsequent hAb responses. We found that CB6F1 mice infected with A/CA followed by immunization with A/PR8 have increased hAb responses to A/PR8 compared to C57BL/6 mice. Increased hAb responses in CB6F1 mice were CD4+ T-cell and B-cell dependent and corresponded to increased germinal center A/PR8-specific B and T-follicular helper cells. These results suggest conserved MHC Class II restricted epitopes within HA are essential for B cells to respond to drifting influenza and could be leveraged to boost hAb responses.
Asunto(s)
Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Inmunización , Memoria Inmunológica , Virus de la Influenza A/inmunología , Animales , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Femenino , RatonesRESUMEN
Background: Prevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV). Methods: Blood samples were taken pre-, 14 days, 28 days, and 1 year after a primary VZV vaccination (Zostavax) at middle age (N = 53, 50-65 years of age). VZV-specific IFNγ-producing cells were measured by ELISpot, activated T-cells by flow cytometry, antibody levels and cytokine responses by fluorescent bead-based multiplex immunoassays, and whole blood cellular kinetics by TruCOUNT analysis. Results: Robust short-term enhancement of the VZV-specific IFNγ-producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFNγ-producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFNγ-producing cells, who were significantly older. These participants also showed enhancement of VZV-specific activated CD4 T-cells, contrary to "exhausted" VZV-specific CD8 T-cells in participants with high numbers of VZV-specific pre-vaccination IFNγ-producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFNγ-producing cells. Conclusion: These results suggest that adults in their early sixties, who showed a high CD4/CD8 T-cell ratio and low numbers of VZV-specific IFNγ-producing cells, benefit from VZV vaccination. This provides important knowledge on factors affecting VZV-specific immune responses in middle-aged adults as well as for strategies to strengthen immunity before reaching old age.