peptide vaccine Dotaz Zobrazit nápovědu
Acta pathologica, microbiologica et immunologica scandinavica. No. 62, ISSN 0903-465X Supplement Vol. 104
28 s. : il. ; 30 cm
Ixodes ricinus and Ixodes scapularis are the main vectors for the causative agents of Lyme borreliosis and a wide range of other pathogens. Repeated tick-bites are known to lead to tick rejection; a phenomenon designated as tick immunity. Tick immunity is mainly directed against tick salivary gland proteins (TSGPs) and has been shown to partially protect against experimental Lyme borreliosis. TSGPs recognized by antibodies from tick immune animals could therefore be interesting candidates for an anti-tick vaccine, which might also block pathogen transmission. To identify conserved Ixodes TSGPs that could serve as a universal anti-tick vaccine in both Europe and the US, a Yeast Surface Display containing salivary gland genes of nymphal I. ricinus expressed at 24, 48 and 72 h into tick feeding was probed with either sera from rabbits repeatedly exposed for 24 h to I. ricinus nymphal ticks and/or sera from rabbits immune to I. scapularis. Thus, we identified thirteen TSGP vaccine candidates, of which ten were secreted. For vaccination studies in rabbits, we selected six secreted TSGPs, five full length and one conserved peptide. None of these proteins hampered tick feeding. In contrast, vaccination of guinea pigs with four non-secreted TSGPs - two from the current and two from a previous human immunoscreening - did significantly reduce tick attachment and feeding. Therefore, non-secreted TSGPs appear to be involved in the development of tick immunity and are interesting candidates for an anti-tick vaccine.
Downregulation of MHC class I expression on the cell surface is a common mechanism by which tumour cells, including cervical carcinoma, can escape the T cell-mediated anti-tumour immunity. This downregulation represents an obstacle for the efficacy of anti-tumour vaccines. In this study, we investigated the efficacy of prophylactic peptide and peptide-pulsed dendritic cell-based vaccines in a murine model of experimental MHC class I-deficient tumours (TC-1/A9), expressing E6/E7 oncogenes derived from HPV16, and compared the efficacy of particular vaccination settings to anti-tumour protection against parental MHC class I-positive TC-1 tumours. Peptide vaccine based on the 'short' peptide E749-57 harbouring solely the CTL epitope and co-administered to the C57BL/6 mice with CpG oligodeoxynucleotide (CpG ODN) 1826 was effective against MHC class I-positive but not -deficient tumours, while the 'longer' peptide E744-62 (peptide 8Q, harbouring CTL and Th epitopes)-based vaccines were also effective against MHC class I-deficient tumours. We have compared the adjuvant efficacies of two CpG ODN, CpG ODN 1826 and CpG ODN 1585. The 8Q peptide immunisation combined with CpG ODN 1585 inhibited growth of the TC-1/A9 tumours more effectively as compared to CpG ODN 1826. Further, we investigated the efficacy of cellular vaccines based on ex vivo cultured dendritic cells pulsed with either E749-57 or E744-62 peptides and matured with CpG ODN 1826. Unlike in the peptide immunisation setting, treatment with dendritic cells pulsed with a 'short' peptide resulted in the tumour growth inhibition, albeit weaker as compared to the immunisation with the longer peptide. Our data demonstrate that peptide and dendritic cell-based vaccines can be designed to elicit protective immunity against MHC class I-deficient tumours.
- MeSH
- adjuvantní radioterapie metody MeSH
- CpG ostrůvky MeSH
- dendritické buňky cytologie MeSH
- epitopy chemie MeSH
- geny MHC třídy I MeSH
- lidé MeSH
- myši MeSH
- oligonukleotidy genetika MeSH
- Papillomavirus E7 - proteiny chemie MeSH
- peptidy chemie MeSH
- protinádorové vakcíny chemie MeSH
- průtoková cytometrie MeSH
- regulace genové exprese MeSH
- subjednotkové vakcíny genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
The control of ticks through vaccination offers a sustainable alternative to the use of chemicals that cause contamination and the selection of resistant tick strains. However, only a limited number of anti-tick vaccines have reached commercial realization. In this sense, an antigen effective against different tick species is a desirable target for developing such vaccines. A peptide derived from the tick P0 protein (pP0) conjugated to a carrier protein has been demonstrated to be effective against the Rhipicephalus microplus, Rhipicephalus sanguineus, and Amblyomma mixtum tick species. The aim of this work was to assess the efficacy of this peptide when conjugated to the Bm86 protein against Dermacentor nitens and Ixodes ricinus ticks. An RNAi experiment using P0 dsRNA from I. ricinus showed a dramatic reduction in the feeding of injected female ticks on guinea pigs. In the follow-up vaccination experiments, rabbits were immunized with the pP0-Bm86 conjugate and challenged simultaneously with larvae, nymphs, and the adults of I. ricinus ticks. In the same way, horses were immunized with the pP0-Bm86 conjugate and challenged with D. nitens larva. The pP0-Bm86 conjugate showed efficacies of 63% and 55% against I. ricinus and D. nitens ticks, respectively. These results, combined with previous reports of efficacy for this conjugate, show the promising potential for its development as a broad-spectrum anti-tick vaccine.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The immune response to vaccination in hemodialysis (HD) patients can be influenced by disorders of iron metabolism, iron overload or chronic inflammatory state. Elevated levels of hepcidin are considered a new marker of iron metabolism impairment and anemia of inflammation in HD patients. METHODS: We studied the effects of hepcidin, other markers of iron status and intravenous iron (Fe(iv)) on the response to an influenza vaccine (Influvac(R) subunit 2008/2009) in 40 HD patients. The immune response of HD patients was compared with that of 46 controls without renal disease according to serum antihemagglutinin antibody titer (anti-HA). RESULTS: A total of 31 HD patients (responders) attained seroconversion (at least a 4-fold increase in anti-HA) to at least 1 of 3 vaccine strains; 9 patients (nonresponders) did not respond to any strain. Responders did not differ from nonresponders in hepcidin [99 microg/l (36-200) vs. 97 microg/l (23-216), p = 0.97]. Responders had lower ferritin (571 +/- 291 vs. 821 +/- 309 microg/l, p = 0.031) and were administered higher doses of Fe(iv) within the last 12 weeks prior to vaccination [625 mg (312-625) vs. 312 mg (0-625), p = 0.029]. The seroconversion to A(H1N1), A(H3N2) and B strains was noted in 20, 52 and 40% of HD and in 11, 39 and 48% of controls, respectively (HD vs. controls, p = nonsignificant). The rates of seroprotection (anti-HA > or =40) to vaccine strains in HD (27, 85 and 95%) and controls (24, 96 and 98%) were also comparable. CONCLUSION: Antibody production following influenza vaccination in HD patients may be suppressed by very high ferritin levels. Hepcidin does not correlate with immune response and high levels of hepcidin may reflect its retention in HD patients. Fe(iv) administration was not associated with a poorer immune response. The immunogenicity of the A(H1N1) strain was inadequate in HD patients and controls alike.
- MeSH
- biologické markery krev MeSH
- dialýza ledvin MeSH
- ferritiny krev imunologie MeSH
- kationické antimikrobiální peptidy krev imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protilátky virové biosyntéza krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vakcíny proti chřipce imunologie terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Tattooing has been shown to be very efficient at inducing immunity by vaccination with DNA vaccines. In this study, we examined the usability of tattooing for delivery of peptide vaccines. We compared tattooing with subcutaneous (s.c.) needle injection using peptides derived from human papillomavirus type 16 (HPV16) proteins. We observed that higher peptide-specific immune responses were elicited after vaccination with the simple peptides (E7(44-62) and E7(49-57)) and keyhole limpet hemocyanin-(KLH)-conjugated peptides (E7(49-57), L2(18-38) and L2(108-120)) with a tattoo device compared to s.c. inoculation. The administration of the synthetic oligonucleotide containing immunostimulatory CpG motifs (ODN1826) enhanced the immune responses developed after s.c. injection of some peptides (E7(44-62), KLH-conjugated L2(18-38) and L2(108-120)) to levels close to or even comparable to those after tattoo delivery of identical peptides with ODN1826. The highest efficacy of tattooing was observed in combination with ODN1826 for the vaccination with the less immunogenic E6(48-57) peptide and KLH-conjugated and non-conjugated E7(49-57) peptides which form the visible aggregates that could negatively influence the development of immune responses after s.c. injection but probably not after tattooing. In summary, we first evidenced that tattoo administration of peptide vaccines that might be useful in some cases efficiently induced both humoral and cell-mediated immune responses.
- MeSH
- cytotoxické T-lymfocyty imunologie MeSH
- DNA vakcíny imunologie MeSH
- hemokyanin imunologie MeSH
- lidský papilomavirus 16 imunologie MeSH
- molekulární sekvence - údaje MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- onkogenní proteiny virové imunologie MeSH
- Papillomavirus E7 - proteiny MeSH
- peptidové fragmenty MeSH
- represorové proteiny imunologie MeSH
- sekvence aminokyselin MeSH
- tetování MeSH
- vakcinace MeSH
- vakcíny proti papilomavirům imunologie MeSH
- virové plášťové proteiny imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Vaccine strategies for the treatment of human papillomavirus-induced cervical cancer are based mainly on the human papillomavirus 16 E7 (HPV16 E7) oncoprotein. The immunogenicity of the E7 gene has been enhanced by its fusion to many different genes. Here, we linked a short sequence coding for the E7 peptide (aa 44-60) containing immunodominant epitopes for B and T cells to the 3' end of the gene coding for the whole coat protein (CP) of the poty-virus, potato virus A (PVA), and its deleted form (CPdel) with a short C-terminal deletion of 5 amino acids (LGVKG). CP-E7 and CPdel-E7 fusion proteins, just like CP alone, spontaneously assembled into virus-like particles in both procaryotic and eucaryotic cells. The CP-E7 and CPdel-E7 fusion genes induced slightly stronger E7-specific cytotoxic T-lymphocyte responses than the whole E7 gene, although they were still lower than those elicited by the previously constructed fusion gene, Sig/E7GGG/LAMP-1. The E7- and CP-specific antibody responses were not detected in mice vaccinated with CP-E7 and CPdel-E7 fusion genes. The CP-E7 and CPdel-E7 fusion genes protected mice against the development of tumors induced by TC-1 cells producing the E7 antigen and were also effective in the therapeutic setting, i.e. when the vaccination was performed after tumor cell administration. Their antitumor effect was comparable to those of the whole E7 gene and Sig/E7GGG/LAMP-1 fusion gene. There was no relevant difference between immune responses elicited by CP-E7 and CPdel-E7 DNA vaccination.
- MeSH
- biolistika MeSH
- buněčné linie MeSH
- buňky NIH 3T3 MeSH
- časové faktory MeSH
- cytotoxické T-lymfocyty cytologie MeSH
- DNA vakcíny MeSH
- ELISA MeSH
- financování organizované MeSH
- genetická terapie metody MeSH
- hmotnostní spektrometrie MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- onkogenní proteiny virové chemie MeSH
- peptidy chemie MeSH
- plazmidy metabolismus MeSH
- Potyvirus genetika MeSH
- protinádorové látky farmakologie MeSH
- protinádorové vakcíny MeSH
- rekombinantní fúzní proteiny chemie MeSH
- RNA chemie MeSH
- sekvence aminokyselin MeSH
- sekvenční homologie aminokyselin MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- technika přenosu genů MeSH
- transmisní elektronová mikroskopie MeSH
- transplantace nádorů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- MeSH
- cytotoxické T-lymfocyty imunologie MeSH
- dendritické buňky imunologie MeSH
- finanční podpora výzkumu jako téma MeSH
- imunoterapie metody MeSH
- myši MeSH
- Papillomaviridae imunologie MeSH
- peptidy imunologie MeSH
- protinádorové vakcíny terapeutické užití MeSH
- slezina imunologie MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
