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

ABSTRACT: 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.

SUBMITTER: Rampling T

PROVIDER: S-EPMC6177476 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Rampling Tommy T Ewer Katie J KJ Bowyer Georgina G Edwards Nick J NJ Wright Danny D Sridhar Saranya S Payne Ruth R Powlson Jonathan J Bliss Carly C Venkatraman Navin N Poulton Ian D ID de Graaf Hans H Gbesemete Diane D Grobbelaar Amy A Davies Huw H Roberts Rachel R Angus Brian B Ivinson Karen K Weltzin Rich R Rajkumar Bebi-Yassin BY Wille-Reece Ulrike U Lee Cynthia C Ockenhouse Chris C Sinden Robert E RE Gerry Stephen C SC Lawrie Alison M AM Vekemans Johan J Morelle Danielle D Lievens Marc M Ballou Ripley W RW Lewis David J M DJM Cooke Graham S GS Faust Saul N SN Gilbert Sarah S Hill Adrian V S AVS

NPJ vaccines 20181009

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 ...[more]

PMID: 30323956

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Project description:The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.

Dataset Information

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

Publications

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

Similar Datasets

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