Safety and efficacy of novel malaria vaccine regimens of RTS,S/AS01B alone, or with concomitant ChAd63-MVA-vectored vaccines expressing ME-TRAP

We assessed a combination multi-stage malaria vaccine schedule in which RTS,S/AS01B was given concomitantly with viral vectors expressing multiple-epitope thrombospondin-related adhesion protein (ME-TRAP) in a 0-month, 1-month, and 2-month schedule. RTS,S/AS01B was given as either three full doses or with a fractional (1/5th) third dose. Efficacy was assessed by controlled human malaria infection (CHMI). Safety and immunogenicity of the vaccine regimen was also assessed. Forty-one malaria-naive adults received RTS,S/AS01B at 0, 4 and 8 weeks, either alone (Groups 1 and 2) or with ChAd63 ME-TRAP at week 0, and modified vaccinia Ankara (MVA) ME-TRAP at weeks 4 and 8 (Groups 3 and 4). Groups 2 and 4 received a fractional (1/5th) dose of RTS,S/AS01B at week 8. CHMI was delivered by mosquito bite 11 weeks after first vaccination. Vaccine efficacy was 6/8 (75%), 8/9 (88.9%), 6/10 (60%), and 5/9 (55.6%) of subjects in Groups 1, 2, 3, and 4, respectively. Immunological analysis indicated significant reductions in anti-circumsporozoite protein antibodies and TRAP-specific T cells at CHMI in the combination vaccine groups. This reduced immunogenicity was only observed after concomitant administration of the third dose of RTS,S/AS01B with the second dose of MVA ME-TRAP. The second dose of the MVA vector with a four-week interval caused significantly higher anti-vector immunity than the first and may have been the cause of immunological interference. Co-administration of ChAd63/MVA ME-TRAP with RTS,S/AS01B led to reduced immunogenicity and efficacy, indicating the need for evaluation of alternative schedules or immunization sites in attempts to generate optimal efficacy

Corrigendum to “Heterologous Two-dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-lasting Cellular Immunity to Influenza Virus A in Healthy Adults” [EBioMedicine 29 (2018) 146–154] (S2352396418300653) (10.1016/j.ebiom.2018.02.011))

The authors wish to point out that L. Coughlan and S. Sridhar were both at the Jenner Institute, University of Oxford, OX3 7DQ, UK, when the work for the paper was completed.</p

Post Hoc Analysis Of The Patricia Randomized Trial Of The Efficacy Of Human Papillomavirus Type 16 (hpv-16)/hpv-18 As04-adjuvanted Vaccine Against Incident And Persistent Infection With Nonvaccine Oncogenic Hpv Types Using An Alternative Multiplex Type-specific Pcr Assay For Hpv Dna

The efficacy of the human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against cervical infections with HPV in the Papilloma Trial against Cancer in Young Adults (PATRICIA) was evaluated using a combination of the broad-spectrum L1-based SPF10 PCR-DNA enzyme immunoassay (DEIA)/line probe assay (LiPA25) system with type-specific PCRs for HPV-16 and -18. Broad-spectrum PCR assays may underestimate the presence of HPV genotypes present at relatively low concentrations in multiple infections, due to competition between genotypes. Therefore, samples were retrospectively reanalyzed using a testing algorithm incorporating the SPF10 PCR-DEIA/LiPA25 plus a novel E6-based multiplex type-specific PCR and reverse hybridization assay (MPTS12 RHA), which permits detection of a panel of nine oncogenic HPV genotypes (types 16, 18, 31, 33, 35, 45, 52, 58, and 59). For the vaccine against HPV types 16 and 18, there was no major impact on estimates of vaccine efficacy (VE) for incident or 6-month or 12-month persistent infections when the MPTS12 RHA was included in the testing algorithm versus estimates with the protocol-specified algorithm. However, the alternative testing algorithm showed greater sensitivity than the protocol-specified algorithm for detection of some nonvaccine oncogenic HPV types. More cases were gained in the control group than in the vaccine group, leading to higher point estimates of VE for 6-month and 12-month persistent infections for the nonvaccine oncogenic types included in the MPTS12 RHA assay (types 31, 33, 35, 45, 52, 58, and 59). This post hoc analysis indicates that the per-protocol testing algorithm used in PATRICIA underestimated the VE against some nonvaccine oncogenic HPV types and that the choice of the HPV DNA testing methodology is important for the evaluation of VE in clinical trials. (This study has been registered at ClinicalTrials.gov under registration no. NCT00122681.).222235244Walboomers, J.M., Jacobs, M.V., Manos, M.M., Bosch, F.X., Kummer, J.A., Shah, K.V., Snijders, P.J., Muñoz, N., Human papillomavirus is a necessary cause of invasive cervical cancer worldwide (1999) J Pathol, 189, pp. 12-19. , http://dx.doi.org/10.1002/(SICI)1096-9896(199909)189:1_12::AID-PATH431_3.0.CO;2-FDe Sanjosé, S., Quint, W.G., Alemany, L., Geraets, D.T., Klaustermeier, J.E., Lloveras, B., Tous, S., Puras, A., Human papillomavirus genotype attribution in invasive cervical cancer: A retrospective cross-sectional worldwide study (2010) Lancet Oncol, 11, pp. 1048-1056. , http://dx.doi.org/10.1016/S1470-2045(10)70230-8Li, N., Franceschi, S., Howell-Jones, R., Snijders, P.J., Clifford, G.M., Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication (2011) Int J Cancer, 128, pp. 927-935. , http://dx.doi.org/10.1002/ijc.25396Guan, P., Howell-Jones, R., Li, N., Bruni, L., De Sanjose, S., Franceschi, S., Clifford, G.M., Human papillomavirus types in 115,789 hpvpositive women: A meta-analysis from cervical infection to cancer (2012) Int J Cancer, 131, pp. 2349-2359. , http://dx.doi.org/10.1002/ijc.27485Tjalma, W.A., Fiander, A., Reich, O., Powell, N., Nowakowski, A.M., Kirschner, B., Koiss, R., Holl, K., Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in europe (2013) Int J Cancer, 132, pp. 854-867. , http://dx.doi.org/10.1002/ijc.27713Descamps, D., Hardt, K., Spiessens, B., Izurieta, P., Verstraeten, T., Breuer, T., Dubin, G., Safety of human papillomavirus (hpv)-16/18 as04- adjuvanted vaccine for cervical cancer prevention: A pooled analysis of 11 clinical trials (2009) Hum Vaccin, 5, pp. 332-340. , http://dx.doi.org/10.4161/hv.5.5.7211Harper, D.M., Franco, E.L., Wheeler, C., Ferris, D.G., Jenkins, D., Schuind, A., Zahaf, T., Dubin, G., Efficacy of a bivalent l1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: A randomised controlled trial (2004) Lancet, 364, pp. 1757-1765. , http://dx.doi.org/10.1016/S0140-6736(04)17398-4Harper, D.M., Franco, E.L., Wheeler, C.M., Moscicki, A.B., Romanowski, B., Roteli-Martins, C.M., Jenkins, D., Dubin, G., Sustained efficacy up to 4.5 years of a bivalent l1 virus-like particle vaccine against human papillomavirus types 16 and 18: Follow-up from a randomised control trial (2006) Lancet, 367, pp. 1247-1255. , http://dx.doi.org/10.1016/S0140-6736(06)68439-0Sustained efficacy and immunogenicity of the human papillomavirus (hpv)-16/18 as04-adjuvanted vaccine: Analysis of a randomised placebo-controlled trial up to 6.4 years (2009) Lancet, 374, pp. 1975-1985. , http://dx.doi.org/10.1016/S0140-6736(09)61567-1De Carvalho, N., Teixeira, J., Roteli-Martins, C.M., Naud, P., De Borba, P., Zahaf, T., Sanchez, N., Schuind, A., Sustained efficacy and immunogenicity of the hpv-16/18 as04-adjuvanted vaccine up to 7.3 years in young adult women (2010) Vaccine, 28, pp. 6247-6255. , http://dx.doi.org/10.1016/j.vaccine.2010.07.007Paavonen, J., Jenkins, D., Bosch, F.X., Naud, P., Salmeron, J., Wheeler, C.M., Chow, S.N., Dubin, G., Efficacy of a prophylactic adjuvanted bivalent l1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: An interim analysis of a phase iii double-blind, randomised controlled trial (2007) Lancet, 369, pp. 2161-2170. , http://dx.doi.org/10.1016/S0140-6736(07)60946-5Paavonen, J., Naud, P., Salmeron, J., Wheeler, C.M., Chow, S.N., Apter, D., Kitchener, H., Greenacre, M., Efficacy of human papillomavirus (hpv)-16/18 as04- adjuvanted vaccine against cervical infection and precancer caused by oncogenic hpv types (patricia): Final analysis of a double-blind, randomised study in young women (2009) Lancet, 374, pp. 301-314. , http://dx.doi.org/10.1016/S0140-6736(09)61248-4Lehtinen, M., Paavonen, J., Wheeler, C.M., Jaisamrarn, U., Garland, S.M., Castellsague, X., Skinner, S.R., Dubin, G., Overall efficacy of hpv-16/18 as04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind patricia trial (2012) Lancet Oncol, 13, pp. 89-99. , http://dx.doi.org/10.1016/S1470-2045(11)70286-8Wheeler, C.M., Castellsague, X., Garland, S.M., Szarewski, A., Paavonen, J., Naud, P., Salmeron, J., Lehtinen, M., Cross-protective efficacy of hpv-16/18 as04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic hpv types: 4-year endof- study analysis of the randomised, double-blind patricia trial (2012) Lancet Oncol, 13, pp. 100-110. , http://dx.doi.org/10.1016/S1470-2045(11)70287-XTota, J.E., Ramanakumar, A.V., Jiang, M., Dillner, J., Walter, S.D., Kaufman, J.S., Coutlee, F., Franco, E.L., Epidemiologic approaches to evaluating the potential for human papillomavirus type replacement postvaccination (2013) Am J Epidemiol, 178, pp. 625-634. , http://dx.doi.org/10.1093/aje/kwt018Van Doorn, L.J., Molijn, A., Kleter, B., Quint, W., Colau, B., Highly effective detection of human papillomavirus 16 and 18 dna by a testing algorithm combining broad-spectrum and type-specific pcr (2006) J Clin Microbiol, 44, pp. 3292-3298. , http://dx.doi.org/10.1128/JCM.00539-06Quint, W.G., Scholte, G., Van Doorn, L.J., Kleter, B., Smits, P.H., Lindeman, J., Comparative analysis of human papillomavirus infections in cervical scrapes and biopsy specimens by general spf(10) pcr and hpv genotyping (2001) J Pathol, 194, pp. 51-58. , http://dx.doi.org/10.1002/path.855Wheeler, C.M., Kjaer, S.K., Sigurdsson, K., Iversen, O.E., Hernandez-Avila, M., Perez, G., Brown, D.R., Barr, E., The impact of quadrivalent human papillomavirus (hpvTypes 6, 11, 16, and 18) l1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine hpv types in sexually active women aged 16-26 years (2009) J Infect Dis, 199, pp. 936-944. , http://dx.doi.org/10.1086/597309Van Alewijk, D., Kleter, B., Vent, M., Delroisse, J.M., De Koning, M., Van Doorn, L.J., Quint, W., Colau, B., A human papilloma virus testing algorithm comprising a combination of the l1 broad-spectrum spf10 pcr assay and a novel e6 high-risk multiplex type-specific genotyping pcr assay (2013) J Clin Microbiol, 51, pp. 1171-1178. , http://dx.doi.org/10.1128/JCM.02831-12Kleter, B., Van Doorn, L.J., Ter Schegget, J., Schrauwen, L., Van Krimpen, K., Burger, M., Ter Harmsel, B., Quint, W., Novel short-fragment pcr assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses (1998) Am J Pathol, 153, pp. 1731-1739. , http://dx.doi.org/10.1016/S0002-9440(10)65688-XKleter, B., Van Doorn, L.J., Schrauwen, L., Molijn, A., Sastrowijoto, S., Ter Schegget, J., Lindeman, J., Quint, W., Development and clinical evaluation of a 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(2013) Eur J Obstet Gynecol Reprod Biol, 170, pp. 45-46. , http://dx.doi.org/10.1016/j.ejogrb.2013.06.027Palmroth, J., Merikukka, M., Paavonen, J., Apter, D., Eriksson, T., Natunen, K., Dubin, G., Lehtinen, M., Occurrence of vaccine and non-vaccine human papillomavirus types in adolescent finnish females 4 years postvaccination (2012) Int J Cancer, 131, pp. 2832-2838. , http://dx.doi.org/10.1002/ijc.27586Pagliusi, S.R., Aguado, M.T., Efficacy and other milestones for human papillomavirus vaccine introduction (2004) Vaccine, 23, pp. 569-578. , http://dx.doi.org/10.1016/j.vaccine.2004.07.046(2011) Fifty-seventh Report World Health Organization Technical Report Series 962, , http://apps.who.int/medicinedocs/documents/s19540en/s19540en.pdf, World Health Organization Expert Committee on Biological Standardization. World Health Organization, Geneva, Switzerlan

Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

Pathophysiology, epidemiology and therapy of agein

Prediction of non-bandlimited signals from past samples in terms of splines of low degree Dedicated to Professor Hans Triebel on the occasion of his 50th birthday

SIGLETIB: RN 2414 (327) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman