Tick-borne encephalitis virus (TBEV) is a tick-borne flavivirus that induces severe central nervous system disorders. It has recently raised concerns due to an expanding geographical range and increasing infection rates. Existing vaccines, though effective, face low coverage rates in numerous TBEV endemic regions. Our previous work demonstrated the immunogenicity and full protection afforded by a TBEV vaccine based on virus-like particles (VLPs) produced in Leishmania tarentolae cells in immunization studies in a mouse model. In the present study, we explored the impact of adjuvants (AddaS03TM, Alhydrogel®+MPLA) and administration routes (subcutaneous, intramuscular) on the immune response. Adjuvanted groups exhibited significantly enhanced antibody responses, higher avidity, and more balanced Th1/Th2 response. IFN-γ responses depended on the adjuvant type, while antibody levels were influenced by both adjuvant and administration routes. The combination of Leishmania-derived TBEV VLPs with Alhydrogel® and MPLA via intramuscular administration emerged as a highly promising prophylactic vaccine candidate, eliciting a robust, balanced immune response with substantial neutralization potential.
- MeSH
- adjuvancia imunologická * aplikace a dávkování MeSH
- adjuvantní vakcína aplikace a dávkování MeSH
- imunogenicita vakcíny MeSH
- injekce intramuskulární MeSH
- interferon gama imunologie MeSH
- klíšťová encefalitida * prevence a kontrola imunologie MeSH
- Leishmania * imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- neutralizující protilátky krev imunologie MeSH
- protilátky virové * krev imunologie MeSH
- syntetické vakcíny * imunologie aplikace a dávkování MeSH
- Th1 buňky imunologie MeSH
- virové vakcíny * imunologie aplikace a dávkování MeSH
- viry klíšťové encefalitidy * imunologie MeSH
- VLP vakcíny * imunologie aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- aktivační mutace imunologie MeSH
- COVID-19 imunologie MeSH
- imunogenicita vakcíny imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mRNA vakcíny škodlivé účinky imunologie MeSH
- protilátky virové imunologie MeSH
- SARS-CoV-2 imunologie MeSH
- syntetické vakcíny škodlivé účinky imunologie MeSH
- transkripční faktor STAT1 imunologie MeSH
- vakcíny proti COVID-19 škodlivé účinky imunologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is highly immunogenic and efficacious in adults ≥50 years of age. We evaluated (1) long-term immunogenicity of an initial 2-dose RZV schedule, by following up adults vaccinated at ≥60 years of age and by modeling, and (2) immunogenicity of 2 additional doses administered 10 years after initial vaccination. METHODS: Persistence of humoral and cell-mediated immune (CMI) responses to 2 initial RZV doses was assessed through 10 years after initial vaccination, and modeled through 20 years using a Piecewise, Power law and Fraser model. The immunogenicity and safety of 2 additional RZV doses were also evaluated. RESULTS: Seventy adults were enrolled. Ten years after initial vaccination, humoral and CMI responses were approximately 6-fold and 3.5-fold, respectively, above those before the initial vaccination levels. Predicted immune persistence through 20 years after initial vaccination was similar across the 3 models. Sixty-two participants (mean age [standard deviation], 82.6 [4.4] years) received ≥1 additional RZV dose. Strong anamnestic humoral and CMI responses were elicited by 1 additional dose, without further increases after a second additional dose. CONCLUSIONS: Immune responses to an initial 2-dose RZV course persisted for many years in older adults. Strong anamnestic immune responses can be induced by additional dosing 10 years after the initial 2-dose course. CLINICAL TRIALS REGISTRATION: NCT02735915.
- MeSH
- adjuvancia imunologická aplikace a dávkování škodlivé účinky MeSH
- herpes zoster prevence a kontrola MeSH
- imunogenicita vakcíny * MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- syntetické vakcíny aplikace a dávkování škodlivé účinky imunologie MeSH
- vakcína proti pásovému oparu aplikace a dávkování škodlivé účinky MeSH
- vakcinace MeSH
- virus varicella zoster imunologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ).Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment.At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4-97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3-99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant.As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.
- MeSH
- adjuvancia imunologická aplikace a dávkování MeSH
- chronická nemoc MeSH
- herpes zoster prevence a kontrola MeSH
- hostitel s imunodeficiencí MeSH
- interpretace statistických dat MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- postherpetická neuralgie imunologie prevence a kontrola MeSH
- potence vakcíny * MeSH
- rizikové faktory MeSH
- senioři MeSH
- syntetické vakcíny imunologie MeSH
- vakcína proti pásovému oparu aplikace a dávkování imunologie MeSH
- vakcinace 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 III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Viral CC chemokine inhibitor (vCCI) of the clone P13 vaccinia virus (VACV) strain PRAHA lacks eight amino acids in the signal peptide sequence. To study the influence of vCCI on virus biology, a virus with the vCCI gene coding for a prolonged signal sequence was prepared. We found that secreted vCCI attenuated the virus in vivo, and that it correlated with decreased levels of RANTES, eotaxin, TARC, and MDC in the blood in comparison with the parental virus. We determined the influence of vCCI on the CTL response against VACV E3((140-148)) (VGPSNSPTF) and HPV16 E7((49-57)) (RAHYNIVTF) H-2D(b)-restricted epitopes. The examination of the specific CTL response elicited by immunization with the recombinant VACV-expressing tumor-associated HPV16 E7 antigen by IFN-γ ELISPOT showed that the immunogenicity of the recombinant VACV-producing secretory vCCI was similar to that of the parent virus or deletion mutant in the C23L/B29R locus. Immunization with the secretory vCCI-producing recombinant virus has a lower therapeutic anti-tumor effect against TC-1 tumors. Viral CCI downregulated the E7-specific response induced by gene gun immunization with the DNA vaccines pBSC-SigE7 LAMP and pBSC-vCCI. We also observed that the immune response against vCCI elicited by the DNA vaccine did not affect the multiplication of VACV in vivo.
- MeSH
- buněčné linie MeSH
- chemokin CCL17 krev MeSH
- chemokin CCL5 krev MeSH
- chemokiny CC antagonisté a inhibitory krev MeSH
- cytotoxické T-lymfocyty imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové supresorové proteiny krev MeSH
- Papillomavirus E7 - proteiny genetika imunologie MeSH
- proteiny ADAM krev MeSH
- protinádorové vakcíny genetika imunologie MeSH
- sekvenční delece MeSH
- syntetické vakcíny genetika imunologie MeSH
- vakcinace MeSH
- virové proteiny genetika metabolismus MeSH
- virové vakcíny imunologie MeSH
- virus vakcinie genetika imunologie patogenita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Proteins MPT63 and MPT83 which are common for both Mycobacterium tuberculosis and Mycobacterium bovis, due to their high immunogenicity, are thought to play a promising role in the development of immunodiagnostic reagents and vaccines. To enhance the antigenic and immunogenic properties of these proteins, fragments of the mpt83 and mpt63 genes were fused in tandem. In this article we present an effective method for the MPT63-MPT83 fusion product purification by metal-affinity chromatography and in vitro refolding. Our results demonstrate that the antigenic properties of the recombinant proteins obtained are comparable to their native analogues. The anti-rMPT63 and anti-rMPT83 sera were found to be highly reactive against the rMPT63-MPT83 fusion protein, which suggests that the fusion protein retains the antigenic properties of the parent proteins. Our results may potentially contribute to the development of improved diagnostic tools or vaccines against human and/or cattle tuberculosis.
- MeSH
- antigeny bakteriální * analýza genetika imunologie MeSH
- bakteriální proteiny * analýza genetika imunologie MeSH
- buněčná inkluze MeSH
- chromatografie MeSH
- epitopy imunologie MeSH
- Mycobacterium tuberculosis * genetika imunologie MeSH
- rekombinantní fúzní proteiny analýza biosyntéza MeSH
- rekombinantní proteiny biosyntéza terapeutické užití MeSH
- renaturace proteinů MeSH
- sbalování proteinů MeSH
- syntetické vakcíny genetika imunologie MeSH
- techniky amplifikace nukleových kyselin MeSH
- techniky in vitro MeSH
- western blotting MeSH
Therapeutic immunization with double recombinants of vaccinia virus (VACV) co-expressing sTβRII increased rejection of established TC-1 tumors in C57BL/6 mice in comparison with single recombinant expressing SigE7LAMP. Recombinant VACV derived from vaccination strain Praha expressed either the sTβRII (ectodomain) or chimeric protein fused to immunoglobulin Fc fragment (sTβRII-Fc-Jun) under control of two different promotors together with the immunogenic tumor associated antigen HPV16 E7 oncoprotein in a form of SigE7LAMP fusion molecule. The ability of soluble receptors to bind TGF-β in vitro was proved. Immunization of mice with double recombinant viruses and virus expressing SigE7LAMP only led to eliciting similar response of E7 specific CD8+ T cells as detected by IFN-γ ELISPOT.
- MeSH
- experimentální nádory terapie MeSH
- imunizace MeSH
- lidský papilomavirus 16 imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- Papillomavirus E7 - proteiny imunologie MeSH
- protein-serin-threoninkinasy genetika MeSH
- receptory transformujícího růstového faktoru beta genetika MeSH
- syntetické vakcíny imunologie MeSH
- T-lymfocyty imunologie MeSH
- vakcíny proti papilomavirům imunologie MeSH
- virus vakcinie genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hsp90-CA is present in cell wall of Candida pseudohyphae or hyphae-typical pathogenic morphotype for both systemic and mucosal Candida infections. Heat shock protein from Candida albicans (hsp90-CA) is an important target for protective antibodies during disseminated candidiasis of experimental mice and human. His-tagged protein rHsp90 was prepared and used as the antigen for preparation of experimental recombinant liposomal vaccine. Nickel-chelating liposomes (the size around 100nm, PDI≤0.1) were prepared from the mixture of egg phosphatidyl choline and nickel-chelating lipid DOGS-NTA-Ni (molar ratio 95:5%) by hydration of lipid film and extrusion methods. New non-pyrogenic hydrophobised derivative of MDP (C18-O-6-norAbuMDP) was incorporated into liposomes as adjuvans. rHsp90 was attached onto the surface of metallochelating liposomes by metallochelating bond and the structure of these proteoliposomes was studied by dynamic light scattering, AF microscopy, TEM and GPC. The liposomes with surface-exposed C18-O-6-norAbuMDP were well recognised and phagocyted by human dendritic cells in vitro. In vivo the immune response towards this experimental vaccine applied in mice (i.d.) demonstrated both TH1 and TH2 response comparable to FCA, but without any side effects. Metallochelating liposomes with lipophilic derivatives of muramyl dipeptide represent a new biocompatible platform for construction of experimental recombinant vaccines and drug-targeting systems.
- MeSH
- antigeny fungální imunologie metabolismus MeSH
- biokompatibilní potahované materiály metabolismus MeSH
- buněčná imunita MeSH
- Candida imunologie MeSH
- chelátory chemie metabolismus MeSH
- dendritické buňky imunologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- liposomy MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nikl imunologie metabolismus MeSH
- proteiny tepelného šoku HSP90 imunologie metabolismus MeSH
- syntetické vakcíny imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Ixodes ricinus is one the most abundant tick species in Europe and these ticks transmit pathogens causing human and animal diseases. The cattle ticks, Rhipicephalus (Boophilus) spp., affect cattle production in tropical and subtropical regions of the world. Development of vaccines directed against tick proteins may reduce tick infestations and the transmission of tick-borne pathogens. However, a limiting step in tick vaccine development has been the identification of tick protective antigens. Herein, the tick iron metabolism pathway was targeted in an effort to identify new tick protective antigens. Recombinant I. ricinus (IrFER2) and Rhipicephalus microplus (RmFER2) ferritin 2 proteins were expressed in Escherichia coli and used to immunize rabbits and cattle, respectively. Vaccination with IrFER2 reduced I. ricinus tick numbers, weight and fertility in rabbits with an overall vaccine efficacy (E) of 98%. Control of cattle tick, R. microplus and Rhipicephalus annulatus infestations was obtained in vaccinated cattle with overall E of 64% and 72%, respectively. Notably, the efficacy of the RmFER2 vaccine was similar to that obtained with Bm86 against R. microplus. These collective results demonstrated the feasibility of using ferritin 2 to develop vaccines for the control of tick infestations.
- MeSH
- Escherichia coli genetika MeSH
- ferritin antagonisté a inhibitory imunologie izolace a purifikace MeSH
- hmyzí proteiny antagonisté a inhibitory imunologie izolace a purifikace MeSH
- infestace klíšťaty prevence a kontrola veterinární MeSH
- klíště imunologie MeSH
- králíci parazitologie MeSH
- nemoci skotu parazitologie prevence a kontrola MeSH
- Rhipicephalus imunologie MeSH
- skot MeSH
- syntetické vakcíny imunologie MeSH
- zvířata MeSH
- Check Tag
- králíci parazitologie MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The Candida albicans heat shock protein 90 kDa (hsp90-CA) is an important target for protective antibodies in disseminated candidiasis of experimental mice and humans. Hsp90-CA is present in the cell wall of Candida pseudohyphae or hyphae--typical pathogenic morphotypes in both mucosal and systemic Candida infections. However, the potential protective effects of hsp90-CA-specific antibodies in vaginal candidiasis has not yet been reported. In the present study we used various vaccine formulations (recombinant hsp90-CA protein and hsp90-CA-encoding DNA vaccine) and routes of administration (intradermal, intranasal, and intravenous) to induce both hsp90-CA-specific systemic and vaginal mucosa immune responses in experimental BALB/c mice. The results showed that intradermal recombinant hsp90-CA protein priming, followed by intranasal or intradermal recombinant hsp90-CA protein boosting induced significant increases in both serum and vaginal hsp90-CA-specific IgG and IgA antibodies compared to the control group, as well as enhanced hsp90-CA-specific splenocyte responses in vitro. In the intradermally boosted group, subsequent experimental vaginal Candida infection induced additional increases in the hsp90-CA specific IgG isotype, suggesting that Candida has the ability to induce a local hsp90-specific antibody (IgG) response during vulvovaginal candidiasis. Further work is required to elucidate the importance of immunity to highly conserved antigens during infection of the human female reproductive tract where a balance between immunity to and tolerance for commonly antigens such as hsp90 is necessary for the maintenance of fertility.
- MeSH
- aplikace intranazální MeSH
- Candida albicans imunologie MeSH
- DNA vakcíny aplikace a dávkování imunologie MeSH
- financování organizované MeSH
- fungální proteiny imunologie MeSH
- fungální vakcíny aplikace a dávkování imunologie MeSH
- injekce intradermální MeSH
- injekce intravenózní MeSH
- kandidóza vulvovaginální imunologie MeSH
- lymfocyty imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- proliferace buněk MeSH
- proteiny tepelného šoku HSP90 imunologie MeSH
- protilátky fungální analýza krev MeSH
- sekundární imunizace MeSH
- slezina imunologie MeSH
- syntetické vakcíny aplikace a dávkování imunologie MeSH
- tvorba protilátek MeSH
- vagina imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
