We recently reported on a successful vaccine for carp against SVCV based on the intramuscular injection of a DNA plasmid encoding the SVCV glycoprotein (SVCV-G). This shows that the intramuscular (i.m.) route of vaccination is suitable to trigger protective responses against SVCV, and that the SVCV G-protein is a suitable vaccine antigen. Yet, despite the general success of DNA vaccines, especially against fish rhabdoviruses, their practical implementation still faces legislative as well as consumer's acceptance concerns. Furthermore, the i.m. route of plasmid administration is not easily combined with most of the current vaccination regimes largely based on intraperitoneal or immersion vaccination. For this reason, in the current study we evaluated possible alternatives to a DNA-based i.m. injectable vaccine using the SVCV-G protein as the vaccine antigen. To this end, we tested two parallel approaches: the first based on the optimization of an alginate encapsulation method for oral delivery of DNA and protein antigens; the second based on the baculovirus recombinant expression of transmembrane SVCV-G protein in insect cells, administered as whole-cell subunit vaccine through the oral and injection route. In addition, in the case of the oral DNA vaccine, we also investigated the potential benefits of the mucosal adjuvants Escherichia coli lymphotoxin subunit B (LTB). Despite the use of various vaccine types, doses, regimes, and administration routes, no protection was observed, contrary to the full protection obtained with our reference i.m. DNA vaccine. The limited protection observed under the various conditions used in this study, the nature of the host, of the pathogen, the type of vaccine and encapsulation method, will therefore be discussed in details to provide an outlook for future vaccination strategies against SVCV.
- MeSH
- DNA vakcíny aplikace a dávkování klasifikace farmakologie MeSH
- infekce viry z čeledi Rhabdoviridae imunologie prevence a kontrola veterinární virologie MeSH
- kapři * MeSH
- nemoci ryb imunologie prevence a kontrola virologie MeSH
- Rhabdoviridae imunologie MeSH
- Sf9 buňky MeSH
- Spodoptera MeSH
- subjednotkové vakcíny aplikace a dávkování klasifikace farmakologie MeSH
- vakcinace veterinární MeSH
- virové vakcíny aplikace a dávkování klasifikace farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Intratumorózní imunoterapie používá vlastní nádor jako vakcínu. Přímá injikace malých množství imunostimulátorů do nádoru umožňuje vytvoření účinné koncentrace in situ a snižuje jejich nežádoucí účinky. Námi vyvinutý terapeutický přístup zesiluje účinek primárního ataku nádorů na úrovni vrozené imunity a vytváří příznivé podmínky pro antigenní prezentaci a zapojení imunity získané.
Intratumoral immunotherapy is based on the use of autologous tumor as a vaccine. Direct injection of small amount of immunostimulators into the tumor creates effective concentrations in situ and decreases their side effects. Our therapeutic approach amplifies the primary effect of innate immunity and creates favourable conditions for involvement of adaptive immunity.
- MeSH
- antigeny nádorové aplikace a dávkování terapeutické užití MeSH
- imunoterapie * dějiny metody trendy MeSH
- kombinovaná terapie metody trendy MeSH
- lidé MeSH
- melanom farmakoterapie MeSH
- nádory slinivky břišní farmakoterapie MeSH
- protinádorové látky aplikace a dávkování klasifikace terapeutické užití MeSH
- subjednotkové vakcíny aplikace a dávkování terapeutické užití MeSH
- toll-like receptor 9 * agonisté aplikace a dávkování terapeutické užití MeSH
- způsoby aplikace léků * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: In adults aged ≥60 years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) elicited humoral and cell-mediated immune responses persisting for at least six years. We assessed immunogenicity nine years post-initial vaccination. METHODS: This open extension study (NCT02735915) followed 70 participants who received two HZ/su doses in the initial trial (NCT00434577). Blood samples to assess the cellular (intracellular cytokine staining) and humoral (ELISA) immunity were taken at year nine post-initial vaccination. RESULTS: Participants' mean age at dose 1 was 72.3 years. The fold increases over pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing ≥2 activation markers plateaued from year four post-dose 1 until year nine. Anti-gE antibody geometric mean concentrations plateaued and remained above pre-vaccination levels from year four onwards. Immunogenicity at year nine was similar across age strata (60-69, ≥70 years) and confirmed statistical prediction model results using data for up to year six. Further modeling using all data up to year nine predicted immune responses would remain above the pre-vaccination level up to year 15. CONCLUSION: In adults aged ≥60 years, HZ/su-induced immunogenicity remained above pre-vaccination levels for at least nine years post-initial vaccination. SUMMARY: After vaccination with HZ/su, both cell mediated and humoral immunity remained above pre-vaccination levels up to year 9 regardless of age group. Immune responses are predicted to remain above baseline up to 15 years post initial vaccination.
- MeSH
- časové faktory MeSH
- cytokiny analýza MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipid A aplikace a dávkování analogy a deriváty MeSH
- následné studie MeSH
- protilátky virové krev MeSH
- saponiny aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- subjednotkové vakcíny aplikace a dávkování imunologie MeSH
- T-lymfocyty imunologie MeSH
- vakcína proti pásovému oparu aplikace a dávkování imunologie MeSH
- virus varicella zoster imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
Vaccination against influenza is widely used to protect against seasonal flu epidemic although its effectiveness is debated. Here we performed deep quantitative T cell receptor repertoire profiling in peripheral blood of a healthy volunteer in response to trivalent subunit influenza vaccine. We did not observe significant rebuilding of peripheral blood T cell receptors composition in response to vaccination. However, we found several clonotypes in memory T cell fraction that were undetectable before the vaccination and had a maximum concentration at day 45 after vaccine administration. These cells were found in lower concentration in the course of repertoire monitoring for two years period. Our observation suggests a potential for recruitment of only a limited number of new T cells after each seasonal influenza vaccination.
- MeSH
- chřipka lidská prevence a kontrola MeSH
- genetická variace MeSH
- inaktivované vakcíny aplikace a dávkování imunologie MeSH
- klonální evoluce genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory antigenů T-buněk genetika metabolismus MeSH
- subjednotkové vakcíny aplikace a dávkování imunologie MeSH
- T-lymfocyty imunologie metabolismus MeSH
- vakcíny proti chřipce aplikace a dávkování imunologie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. METHODS: This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. RESULTS: No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. CONCLUSIONS: AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. CLINICAL TRIALS REGISTRATION: NCT00802464.
- MeSH
- adjuvancia imunologická MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- herpes zoster prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet CD4 lymfocytů MeSH
- proteiny virového obalu imunologie MeSH
- protilátky virové imunologie MeSH
- senioři MeSH
- subjednotkové vakcíny aplikace a dávkování škodlivé účinky imunologie MeSH
- vakcína proti pásovému oparu aplikace a dávkování škodlivé účinky imunologie MeSH
- virus varicella zoster imunologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
The expression of the transcription factor encoded by the Wilms tumor gene 1 (WT1) is associated with a variety of human cancers. WT1 protein has been reported to serve as a target antigen for tumor-specific immune responses. We observed that the immunization of mice with peptide vaccines derived from WT1 in a mixture with the CpG adjuvant (ODN 1826) by tattoo administration was superior to subcutaneous delivery of the peptides in combination with CpG formulated with the mineral oil adjuvant or a DNA vaccine or a recombinant vaccinia virus vaccine expressing the truncated WT1 protein. Tattooing with the WT1122-140 and WT1126-134 peptide elicited the response of WT1-specific interferon-γ-producing T cells. Peptide vaccine administered with a tattoo device had an antitumor effect on the growth of the prostate tumor cell line TRAMP-C2, provided that the transforming growth factor-β produced by tumor cells was neutralized by anti-TGFβ monoclonal antibody. The treatment of the tumor-bearing mice with 5-azadeoxycytidine or poly IC did not work in synergy with the peptide vaccine.
- MeSH
- adjuvancia imunologická MeSH
- azacytidin analogy a deriváty farmakologie terapeutické užití MeSH
- injekce intradermální MeSH
- monoklonální protilátky imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prostaty terapie MeSH
- poly I-C farmakologie terapeutické užití MeSH
- proteiny WT1 aplikace a dávkování imunologie MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- protinádorové vakcíny aplikace a dávkování MeSH
- subjednotkové vakcíny aplikace a dávkování MeSH
- tetování MeSH
- transformující růstový faktor beta antagonisté a inhibitory imunologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH