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2.
J Headache Pain ; 25(1): 95, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38844851

RESUMEN

BACKGROUND: The pathogenesis of migraine remains unclear; however, a large body of evidence supports the hypothesis that immunological mechanisms play a key role. Therefore, we aimed to review current studies on altered immunity in individuals with migraine during and outside attacks. METHODS: We searched the PubMed database to investigate immunological changes in patients with migraine. We then added other relevant articles on altered immunity in migraine to our search. RESULTS: Database screening identified 1,102 articles, of which 41 were selected. We added another 104 relevant articles. We found studies reporting elevated interictal levels of some proinflammatory cytokines, including IL-6 and TNF-α. Anti-inflammatory cytokines showed various findings, such as increased TGF-ß and decreased IL-10. Other changes in humoral immunity included increased levels of chemokines, adhesion molecules, and matrix metalloproteinases; activation of the complement system; and increased IgM and IgA. Changes in cellular immunity included an increase in T helper cells, decreased cytotoxic T cells, decreased regulatory T cells, and an increase in a subset of natural killer cells. A significant comorbidity of autoimmune and allergic diseases with migraine was observed. CONCLUSIONS: Our review summarizes the findings regarding altered humoral and cellular immunological findings in human migraine. We highlight the possible involvement of immunological mechanisms in the pathogenesis of migraine. However, further studies are needed to expand our knowledge of the exact role of immunological mechanisms in migraine pathogenesis.


Asunto(s)
Trastornos Migrañosos , Humanos , Trastornos Migrañosos/inmunología , Citocinas/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología
3.
PLoS Negl Trop Dis ; 18(6): e0012229, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38857253

RESUMEN

Leishmania donovani surface glycoprotein 63 (GP63) is a major virulence factor involved in parasite escape and immune evasion. In this study, we generated virus-like particles (VLPs) expressing L. donovani GP63 using the baculovirus expression system. Mice were intramuscularly immunized with GP63-VLPs and challenged with L. donovani promastigotes. GP63-VLP immunization elicited higher levels of L. donovani antigen-specific serum antibodies and enhanced splenic B cell, germinal center B cell, CD4+, and CD8+ T cell responses compared to unimmunized controls. GP63-VLPs inhibited the influx of pro-inflammatory cytokines IFN-γ and IL-6 in the livers, as well as thwarting the development of splenomegaly in immunized mice. Upon L. donovani challenge infection, a drastic reduction in splenic parasite burden was observed in VLP-immunized mice. These results indicate that GP63-VLPs immunization conferred protection against L. donovani challenge infection by inducing humoral and cellular immunity in mice.


Asunto(s)
Leishmania donovani , Leishmaniasis Visceral , Ratones Endogámicos BALB C , Vacunas de Partículas Similares a Virus , Animales , Leishmania donovani/inmunología , Ratones , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Femenino , Leishmaniasis Visceral/prevención & control , Leishmaniasis Visceral/inmunología , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Vacunas contra la Leishmaniasis/inmunología , Vacunas contra la Leishmaniasis/administración & dosificación , Eficacia de las Vacunas , Inmunidad Celular , Bazo/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos B/inmunología , Inmunidad Humoral , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/genética , Citocinas/inmunología , Metaloendopeptidasas
4.
Nat Commun ; 15(1): 4913, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851821

RESUMEN

Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.


Asunto(s)
Malaria Falciparum , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos , Superóxido Dismutasa , Animales , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Humanos , Ratones , Neutrófilos/inmunología , Malaria Falciparum/inmunología , Malaria Falciparum/parasitología , Inmunidad Celular , Linfocitos T/inmunología , Plasmodium falciparum/inmunología , Femenino , Interacciones Huésped-Parásitos/inmunología , Interacciones Huésped-Parásitos/genética , Interferón gamma/metabolismo , Interferón gamma/inmunología , Masculino , Inmunidad Innata , Interleucina-2/metabolismo , Interleucina-2/inmunología , Interleucina-2/genética , Parasitemia/inmunología
5.
J Clin Immunol ; 44(6): 147, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856804

RESUMEN

PURPOSE: Asymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a longitudinal cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort). METHODS: Asymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. 51 participant's anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron B.1.1.529.1. RESULTS: Asymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4+ CD45RA+ T cells and activated CD8+ T cells than symptomatic participants, though these differences dissipated after vaccination. CONCLUSIONS: Asymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones Asintomáticas , COVID-19 , Inmunidad Celular , Inmunidad Humoral , SARS-CoV-2 , Humanos , COVID-19/inmunología , SARS-CoV-2/inmunología , Masculino , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Adulto Joven , Adulto , Vacunas contra la COVID-19/inmunología , Estudios de Cohortes , Estudios Longitudinales , Vacunación , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Reino Unido/epidemiología , Adolescente , Glicoproteína de la Espiga del Coronavirus/inmunología
6.
Biochemistry (Mosc) ; 89(5): 872-882, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38880648

RESUMEN

The pandemic of a new coronavirus infection that has lasted for more than 3 years, is still accompanied by frequent mutations in the S protein of SARS-CoV-2 and emergence of new virus variants causing new disease outbreak. Of all coronaviral proteins, the S and N proteins are the most immunogenic. The aim of this study was to compare the features of the humoral and T-cell immune responses to the SARS-CoV-2 S and N proteins in people with different histories of interaction with this virus. The study included 27 individuals who had COVID-19 once, 23 people who were vaccinated twice with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19 and were vaccinated twice with Sputnik V 6-12 months after the disease, and 25 people who had COVID-19 twice. The level of antibodies was determined by the enzyme immunoassay, and the cellular immunity was assessed by the expression of CD107a on CD8high lymphocytes after recognition of SARS-CoV-2 antigens. It was shown that the humoral immune response to the N protein was formed mainly by short-lived plasma cells synthesizing IgG antibodies of all four subclasses with a gradual switch from IgG3 to IgG1. The response to the S protein was formed by short-lived plasma cells at the beginning of the response (IgG1 and IgG3 subclasses) and then by long-lived plasma cells (IgG1 subclass). The dynamics of antibody level synthesized by the short-lived plasma cells was described by the Fisher equation, while changes in the level of antibodies synthesized by the long-lived plasma cells were described by the Erlang equation. The level of antibodies in the groups with the hybrid immunity exceeded that in the group with the post-vaccination immunity; the highest antibody content was observed in the group with the breakthrough immunity. The cellular immunity to the S and N proteins differed depending on the mode of immune response induction (vaccination or disease). Importantly, the response of heterologous CD8+ T cell to the N proteins of other coronaviruses may be involved in the immune defense against SARS-CoV-2.


Asunto(s)
Anticuerpos Antivirales , COVID-19 , Proteínas de la Nucleocápside de Coronavirus , Inmunidad Celular , Inmunidad Humoral , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/virología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Masculino , Persona de Mediana Edad , Femenino , Adulto , Glicoproteína de la Espiga del Coronavirus/inmunología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Vacunas contra la COVID-19/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Fosfoproteínas/inmunología , Linfocitos T CD8-positivos/inmunología , Anciano
7.
Vaccine ; 42(17): 3733-3743, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38705805

RESUMEN

Hand, foot, and mouth disease (HFMD) poses a significant public health threat primarily caused by four major enteroviruses: enterovirus 71 (EV71), coxsackieviruses A16, A10, and A6. Broadly protective immune responses are essential for complete protection against these major enteroviruses. In this study, we designed a new tetravalent immunogen for HFMD, validated it in silico, in vivo evaluated the immunogenicity of the DNA-based tetravalent vaccine in mice, and identified immunogenic B-cell and T-cell epitopes. A new tetravalent immunogen, VP1me, was designed based on the chimeric protein and epitope-based vaccine principles. It contains a complete EV71 VP1 protein and six reported neutralizing B-cell epitopes derived from the four major enteroviruses causing HFMD. In silico validation using multiple immunoinformatic tools indicated good attributes of the VP1me immunogen suitable for vaccine development. The VP1me-based DNA vaccine efficiently induced both humoral and cellular immune responses in BALB/cAJcl mice. A combination of in silico prediction and immunoassays enabled the identification of immunogenic linear B-cell and CD8 T-cell epitopes within the VP1me immunogen. Immunodominant linear B-cell epitopes were identified in six regions of VP1me, with one epitope located at the N-terminus of the VP1 protein (aa 9-23) regarded as a novel epitope. Interestingly, some B-cell epitopes could also induce the CD8 T-cell response, suggesting their dual functions in immune stimulation. These results lay the groundwork for further development of VP1me as a new vaccine candidate.


Asunto(s)
Anticuerpos Antivirales , Epítopos de Linfocito B , Enfermedad de Boca, Mano y Pie , Epítopos Inmunodominantes , Ratones Endogámicos BALB C , Vacunas de ADN , Vacunas Virales , Animales , Vacunas de ADN/inmunología , Epítopos de Linfocito B/inmunología , Enfermedad de Boca, Mano y Pie/prevención & control , Enfermedad de Boca, Mano y Pie/inmunología , Ratones , Vacunas Virales/inmunología , Epítopos Inmunodominantes/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Femenino , Epítopos de Linfocito T/inmunología , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/genética , Enterovirus/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Enterovirus Humano A/inmunología , Enterovirus Humano A/genética , Inmunogenicidad Vacunal , Inmunidad Celular , Inmunidad Humoral
8.
PLoS One ; 19(5): e0303244, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38728294

RESUMEN

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.


Asunto(s)
Vacuna BNT162 , COVID-19 , Personal de Salud , Ensayos de Liberación de Interferón gamma , SARS-CoV-2 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna BNT162/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Inmunidad Celular , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-10/inmunología , Interleucina-6/sangre , Interleucina-6/inmunología , SARS-CoV-2/inmunología , Factor de Necrosis Tumoral alfa/sangre , Vacunación
9.
Yakugaku Zasshi ; 144(5): 475-481, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38692920

RESUMEN

Zinc is one of the essential trace elements, and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, then the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added diet group compared to the normal zinc intake group, and about half the number in the high-zinc-intake group compared to the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. Collectively, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and that it increases the transcription of granzyme B, one of the key molecules involved in tumor immunity. In this symposium, we would like to introduce our latest data on the relationship between zinc and tumor immunity.


Asunto(s)
Neoplasias Colorrectales , Inmunidad Celular , Zinc , Animales , Humanos , Ratones , Azoximetano , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/prevención & control , Modelos Animales de Enfermedad , Granzimas/metabolismo , Linfocitos T Citotóxicos/inmunología
10.
J Control Release ; 370: 691-706, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723671

RESUMEN

Vaccination is essential for preventing and controlling infectious diseases, along with reducing mortality. Developing safe and versatile adjuvants to enhance humoral and cellular immune responses to vaccines remains a key challenge in vaccine development. Here, we designed hierarchical mesoporous MOF-801 (HM801) using a Cocamidopropyl betaine (CAPB) and a Pluronics F127 in an aqueous phase system. Meanwhile, we synthesized a novel SARS-CoV-2 nanovaccine (R@M@HM801) with a high loading capacity for both the STING agonist (MSA-2) and the Delta receptor binding domain (Delta-RBD) antigen. R@M@HM801 enhanced MSA-2 and RBD utilization and effectively co-delivered MSA-2 and RBD antigens to antigen-presenting cells in the draining lymph nodes, thereby promoting the activation of both T and B cells. Lymphocyte single-cell analysis showed that R@M@HM801 stimulated robust CD11b+CD4+ T cells, CXCR5+CD4+ T follicular helper (Tfh), and durable CD4+CD44+CD62L-, CD8+CD44+CD62L- effector memory T cell (TEM) immune responses, and promoted the proliferative activation of CD26+ B cells in vivo. Meanwhile, R@M@HM801 induced stronger specific antibodies and neutralization of pseudovirus against Delta compared to the RBD + MAS-2 and RBD + MAS-2 + Alum vaccines. Our study demonstrated the efficacy of a hierarchical mesoporous HM801 and its potential immune activation mechanism in enhancing adaptive immune responses against viruses and other diseases.


Asunto(s)
Adyuvantes Inmunológicos , Inmunidad Celular , Inmunidad Humoral , Proteínas de la Membrana , Estructuras Metalorgánicas , Animales , Inmunidad Humoral/efectos de los fármacos , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/química , Inmunidad Celular/efectos de los fármacos , Proteínas de la Membrana/inmunología , Ratones , Estructuras Metalorgánicas/química , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , SARS-CoV-2/efectos de los fármacos , Ratones Endogámicos BALB C , Porosidad , Ratones Endogámicos C57BL , Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos
11.
Sci Rep ; 14(1): 12217, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806543

RESUMEN

Patients on hemodialysis (HD) have a high risk of death from COVID-19. We evaluated the humoral and cell-mediated immune response to BNT162b2 (Pfizer-BioNTech) vaccine in HD patients, comparing HD with Poly-methyl-methacrylate (PMMA) and HD with Polysulphone (PS). Samples were collected before vaccination (T0) and 14-days after the 2ndvaccine (T2) in a TG (TG, n = 16-Foggia) and in a VG (CG, n = 36-Novara). Anti-SARS-CoV-2-Ig were titrated in the cohort 2-weeks after the 2nddose of vaccine. In the Testing-Group, serum neutralizing antibodies (NAb) were assayed and PBMCs isolated from patients were thawed, counted and stimulated with SARS-CoV-2 IGRA stimulation tube set. All patients had a positive ab-response, except in a case. PMMA-patients had higher levels of anti-SARS-CoV-2 IgG (p = 0.031); VG data confirmed these findings (p < 0.05). NAb evaluation: PMMA patients passed the positive cut-off value, while in PS group only only 1/8 patient did not respond. PMMA patients showed higher percentages of anti-SARS-CoV-2 S1/RBD-Ig after a complete vaccine schedule (p = 0.028). Interferon-gamma release: PMMA patients showed significantly higher release of IFNγ (p = 0.014). The full vaccination course provided sufficient protection against SARS-CoV-2 across the entire cohort, regardless of dialyzer type. After vaccination, PMMA patients show a better immune response, both humoral and cellular, at the end of the vaccination course than PS patients.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , Polimetil Metacrilato , Diálisis Renal , SARS-CoV-2 , Humanos , Masculino , Femenino , Anciano , COVID-19/inmunología , COVID-19/prevención & control , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna BNT162/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , SARS-CoV-2/inmunología , Polimetil Metacrilato/química , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Estudios de Cohortes , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anciano de 80 o más Años , Vacunación/métodos , Polímeros , Sulfonas
12.
Sci Rep ; 14(1): 12176, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806644

RESUMEN

Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , Trasplante de Riñón , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Trasplante de Riñón/efectos adversos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Femenino , Masculino , Persona de Mediana Edad , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Adulto , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunidad Celular , Vacunación/métodos , Receptores de Trasplantes , Anciano , Inmunización Secundaria
13.
J Nanobiotechnology ; 22(1): 295, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807131

RESUMEN

The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.


Asunto(s)
Señales de Clasificación de Proteína , SARS-CoV-2 , Vacunas de ARNm , Animales , Ratones , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Ratones Endogámicos BALB C , ARN Mensajero/genética , Vacunas contra la COVID-19/inmunología , Femenino , Humanos , Antígenos Virales/inmunología , Antígenos Virales/genética , Antígenos Virales/química , Anticuerpos Antivirales/inmunología , Inmunidad Humoral , Vacunas Sintéticas/inmunología , Inmunidad Celular
14.
Int Immunopharmacol ; 134: 112160, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38710117

RESUMEN

INTRODUCTION: Cholera is a severe gastrointestinal disease that manifests with rapid onset of diarrhea, vomiting, and high mortality rates. Due to its widespread occurrence in impoverished communities with poor water sanitation, there is an urgent demand for a cost-effective and highly efficient vaccine. Multi-epitope vaccines containing dominant immunological epitopes and adjuvant compounds have demonstrated potential in boosting the immune response. MATERIAL AND METHODS: B and T epitopes of OMPU, OMPW, TCPA, CTXA, and CTXB proteins were predicted using bioinformatics methods. Subsequently, highly antigenic multi-epitopes that are non-allergenic and non-toxic were synthesized. These multi-epitopes were then cloned into the pCOMB phagemid. A plasmid M13KO7ΔpIII containing all helper phage proteins except pIII was created to produce the recombinant phage. Female Balb/c mice were divided into three groups and immunized accordingly. The mice received the helper phage, recombinant phage or PBS via gavage feeding thrice within two weeks. Serum samples were collected before and after immunization for the ELISA test as well as evaluating immune system induction through ELISpot testing of spleen lymphocytes. RESULTS: The titer of the recombinant phage was determined to be 1011 PFU/ml. The presence of the recombinant phage was confirmed through differences in optical density between sample and control groups in the ELISA phage technique, as well as by observing transduction activity, which demonstrated successful production of a recombinant phage displaying the Vibrio multi-epitope on M13 phage pIII. ELISA results revealed significant differences in phage antibodies before and after inoculation, particularly notable in the negative control mice. Mice treated with multi-epitope phages exhibited antibodies against Vibrio cholerae lysate. Additionally, ELISpot results indicated activation of cellular immunity in mice receiving both Vibrio and helper phage. CONCLUSION: This study emphasizes the potential of multi-epitope on phage to enhance both cellular and humoral immunity in mice, demonstrating how phages can be used as adjuvants to stimulate mucosal immunity and act as promising candidates for oral vaccination.


Asunto(s)
Anticuerpos Antibacterianos , Vacunas contra el Cólera , Cólera , Inmunidad Celular , Inmunidad Humoral , Ratones Endogámicos BALB C , Vibrio cholerae , Animales , Vibrio cholerae/inmunología , Femenino , Cólera/prevención & control , Cólera/inmunología , Vacunas contra el Cólera/inmunología , Vacunas contra el Cólera/administración & dosificación , Administración Oral , Ratones , Anticuerpos Antibacterianos/sangre , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Inmunización , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genética , Humanos , Bacteriófagos/inmunología , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética
15.
Int Immunopharmacol ; 134: 112141, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38733819

RESUMEN

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.


Asunto(s)
Anticuerpos Antivirales , Inteligencia Artificial , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunas de Productos Inactivados , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Femenino , Vacunas contra la COVID-19/inmunología , Masculino , SARS-CoV-2/inmunología , Persona de Mediana Edad , Adulto , Vacunas de Productos Inactivados/inmunología , Anticuerpos Antivirales/sangre , Estudios Prospectivos , Inmunidad Humoral , Anticuerpos Neutralizantes/sangre , Eficacia de las Vacunas , Inmunización Secundaria , Aprendizaje Automático , Anciano , Adulto Joven , Inmunidad Celular
16.
Toxicology ; 505: 153836, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38768702

RESUMEN

Caramel color is a widely used food pigment, and 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a by-products of Class III caramel color. Some studies have shown that THI can reduce the number of peripheral blood lymphocytes. However, the comprehensive mechanism of THI immunotoxicity requires further study. In this study, the effects of THI on lymphocyte count, humoral immunity, cellular immunity and nonspecific immunity were determined and the effect of the nutritional status of VB6 on THI immunotoxicity was evaluated. Female BALB/c mice were divided into 3 groups and fed chow containing different doses of VB6: VB6-normal (6 mg/kg VB6), VB6-deprived (0.5 mg/kg VB6) or VB6-enhanced (12 mg/kg VB6) feed. Each group was further divided into 4 subgroups and treated with THI (0.5, 2.5 or 12.5 mg/kg bw) or the solvent control by gavage for 30 days. The thymic cortical thickness was measured with ViewPoint; the proportions of major immune cells and T cells in peripheral blood and tissues were detected via flow cytometry; the transformation and proliferation abilities of T and B cells were detected via T and B lymphocyte proliferation assays; NK cell activity was assessed via lactate dehydrogenase assays; humoral immune function was assessed via plaque-forming cell assays; and the immune function of T lymphocytes was assessed via delayed type hypersensitivity assays. The results showed that compared with those in the corresponding control group, the white blood cell count and lymphocyte count decreased significantly in all the VB6-deprived groups, in the 2.5 and 12.5 mg/kg VB6 groups, and in the 12.5 mg/kg VB6-enhanced group. With increasing THI dose, the thymic cortical layer became thinner. In the thymus, THI increased the proportions of CD3+ T cells and mature CD8+ T cells and decreased the proportions of immature double-positive, double-negative T cells and CD69-expressing lymphocytes. The proportions of naïve T cells and Tcm (central memory T) cells related to homing decreased. The proportion of mature T cells in the spleen decreased significantly. The proliferation of T cells stimulated by ConA decreased after THI exposure. VB6-deficient mice were more sensitive to THI immunotoxicity, and supplementation with VB6 had a certain protective effect on these mice. The results of the PFC and NK cell activity assays indicated that THI exposure might not affect humoral immune or innate immune function.


Asunto(s)
Imidazoles , Inmunidad Humoral , Ratones Endogámicos BALB C , Vitamina B 6 , Animales , Femenino , Ratones , Imidazoles/toxicidad , Imidazoles/farmacología , Inmunidad Humoral/efectos de los fármacos , Vitamina B 6/farmacología , Vitamina B 6/administración & dosificación , Recuento de Linfocitos , Estado Nutricional/efectos de los fármacos , Timo/efectos de los fármacos , Timo/inmunología , Inmunidad Celular/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/inmunología , Colorantes de Alimentos/toxicidad , Proliferación Celular/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología
17.
Transpl Infect Dis ; 26(3): e14290, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38708941

RESUMEN

BACKGROUND: Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population. METHODS: In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100. RESULTS: Twenty-eight allo-HCT recipients were enrolled. The median time to first positive CMV-TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV-CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV-CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low-level CMV reactivation, the sensitivity and negative predictive value of CMV-TCIP were 90% and 87.5%, respectively, for CD4+ CMV-TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV-TCIP. CONCLUSIONS: There was significant variability in time to CMV-CMI recovery post-HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV-CMI may protect against CS-CMVi, but immunity may be lost with GVHD diagnosis and treatment.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Infecciones por Citomegalovirus , Citomegalovirus , Citometría de Flujo , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Proyectos Piloto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/prevención & control , Persona de Mediana Edad , Masculino , Citomegalovirus/inmunología , Estudios Prospectivos , Femenino , Citometría de Flujo/métodos , Adulto , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Trasplante Homólogo/efectos adversos , Anciano , Inmunidad Celular , Antivirales/uso terapéutico
18.
Antiviral Res ; 227: 105914, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38759930

RESUMEN

Due to the severity of CMV infection in immunocompromised individuals the development of a vaccine has been declared a priority. However, despite the efforts made there is no yet a vaccine available for clinical use. We designed an approach to identify new CMV antigens able to inducing a broad immune response that could be used in future vaccine formulations. We have used serum samples from 28 kidney transplant recipients, with a previously acquired CMV-specific immune response to identify viral proteins that were recognized by the antibodies present in the patient serum samples by Western blot. A band of approximately 45 kDa, identified as UL44, was detected by most serum samples. UL44 immunogenicity was tested in BALB/c mice that received three doses of the UL44-pcDNA DNA vaccine. UL44 elicited both, a strong antibody response and CMV-specific cellular response. Using bioinformatic analysis we demonstrated that UL44 is a highly conserved protein and contains epitopes that are able to activate CD8 lymphocytes of the most common HLA alleles in the world population. We constructed a UL44 ORF deletion mutant virus that produced no viral progeny, suggesting that UL44 is an essential viral protein. In addition, other authors have demonstrated that UL44 is one of the most abundant viral proteins after infection and have suggested an essential role of UL44 in viral replication. Altogether, our data suggests that UL44 is a potent antigen, and favored by its abundance, it may be a good candidate to include in a vaccine formulation.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Ratones Endogámicos BALB C , Proteínas Virales , Animales , Ratones , Humanos , Citomegalovirus/inmunología , Citomegalovirus/genética , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Proteínas Virales/inmunología , Proteínas Virales/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas de ADN/inmunología , Vacunas de ADN/administración & dosificación , Femenino , Vacunas contra Citomegalovirus/inmunología , Vacunas contra Citomegalovirus/administración & dosificación , Linfocitos T/inmunología , Antígenos Virales/inmunología , Trasplante de Riñón , Linfocitos T CD8-positivos/inmunología , Inmunidad Celular
19.
J Mater Chem B ; 12(24): 5848-5860, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38775048

RESUMEN

Nanoparticles have been regarded as a promising vaccine adjuvant due to their innate immune potentiation and enhanced antigen transport. However, the inefficient infiltration into the lymph node (LN) paracortex of nanoparticles caused by subcapsular sinus (SCS) obstruction is the main challenge in further improvement of nanovaccine immune efficacy. Herein, we propose to overcome paracortex penetration by using nanovaccine to spontaneously and continuously release antigens after retention in the SCS. In detail, we utilized a spontaneous retro-Diels-Alder (r-D-A) reaction linker to connect poly{(2-methyl-2-oxazoline)80-co-[(2-butyl-2-oxazoline)15-r-(2-thioethyl-2-oxazoline)8]} (PMBOxSH) and peptides for the peptide nanovaccine construction. The r-D-A reaction linker can spontaneously break over time, allowing the nanovaccine to release free antigens and adjuvants upon reaching the LN, thereby facilitating the entry of released antigens and adjuvants into the interior of the LNs. We showed that the efficacy of the peptide nanovaccine constructed using this dynamic linker could be significantly improved, thus greatly enhancing the tumor inhibition efficacy in the B16-OVA model. This dynamic-covalent-chemistry-based vaccine strategy may inspire designing more efficient therapeutic vaccines, especially those that require eliciting high-amount T cell responses.


Asunto(s)
Inmunidad Celular , Ganglios Linfáticos , Nanopartículas , Péptidos , Animales , Ratones , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Nanopartículas/química , Péptidos/química , Péptidos/farmacología , Inmunidad Celular/efectos de los fármacos , Ratones Endogámicos C57BL , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/administración & dosificación , Reacción de Cicloadición , Femenino , Tamaño de la Partícula , Nanovacunas
20.
Antiviral Res ; 227: 105917, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38782067

RESUMEN

The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Fragmentos Fc de Inmunoglobulinas , Nanopartículas , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Nanopartículas/química , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Fragmentos Fc de Inmunoglobulinas/inmunología , Fragmentos Fc de Inmunoglobulinas/química , COVID-19/prevención & control , COVID-19/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Animales , Ratones , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/química , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/química , Femenino , Multimerización de Proteína , Ratones Endogámicos BALB C , Desarrollo de Vacunas , Unión Proteica , Inmunogenicidad Vacunal , Inmunidad Celular , Nanovacunas
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