Na-GST-1 and Na-APR-1 are proteins expressed during the adult stage of the Necator americanus hookworm life cycle that are thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. Vaccination wtih recombinant GST-1 or APR-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of co-administering Na-GST-1 and Na-APR-1 to healthy Brazilian adults living in an area of endemic hookworm infection.

开始日期2016-01-01

申办/合作机构

Baylor College of Medicine

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100 项与 Hookworm vaccine(Albert B. Sabin Vaccine Institute, Inc.) 相关的临床结果

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100 项与 Hookworm vaccine(Albert B. Sabin Vaccine Institute, Inc.) 相关的转化医学

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100 项与 Hookworm vaccine(Albert B. Sabin Vaccine Institute, Inc.) 相关的专利（医药）

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项与 Hookworm vaccine(Albert B. Sabin Vaccine Institute, Inc.) 相关的文献（医药）

2024-07-01·The Lancet Infectious Diseases

Safety and immunogenicity of the co-administered Na-APR-1 and Na-GST-1 hookworm vaccines in school-aged children in Gabon: a randomised, controlled, observer-blind, phase 1, dose-escalation trial

Article

作者: Vodonou, Kafui G ; Grobusch, Martin P ; Bethony, Jeffrey M ; Adegnika, Ayola A ; Edoa, Jean Ronald ; Massinga Loembe, Marguerite ; Diemert, David J ; Bottazzi, Maria Elena ; Li, Guangzhao ; Adégbité, Bayodé R ; Hotez, Peter J ; Honkpehedji, Yabo Josiane ; Bikangui, Rodrigue ; Yazdanbakhsh, Maria ; van Leeuwen, Remko ; Zinsou, Jeannot F ; Kremsner, Peter G ; Dejon-Agobé, Jean Claude

BACKGROUNDA human hookworm vaccine is being developed to protect children against iron deficiency and anaemia associated with chronic infection with hookworms. Necator americanus aspartic protease-1 (Na-APR-1) and N americanus glutathione S-transferase-1 (Na-GST-1) are components of the blood digestion pathway critical to hookworm survival in the host. Recombinant Na-GST-1 and catalytically inactive Na-APR-1 (Na-APR-1[M74]) adsorbed to Alhydrogel were safe and immunogenic when delivered separately or co-administered to adults in phase 1 trials in non-endemic and endemic areas. We aimed to investigate the safety and immunogenicity of these antigens in healthy children in a hookworm-endemic area.METHODSThis was a randomised, controlled, observer-blind, phase 1, dose-escalation trial, conducted in a clinical research centre, in 60 children aged six to ten years in Lambaréné, a hookworm-endemic region of Gabon. Healthy children (determined by clinical examination and safety laboratory testing) were randomised 4:1 to receive co-administered Na-GST-1 on Alhydrogel plus Na-APR-1(M74) on Alhydrogel and glucopyranosyl lipid A in aqueous formulation (GLA-AF), or co-administered ENGERIX-B hepatitis B vaccine (HBV) and saline placebo, injected into the deltoid of each arm. Allocation to vaccine groups was observer-masked. In each vaccine group, children were randomised 1:1 to receive intramuscular injections into each deltoid on two vaccine schedules, one at months 0, 2, and 4 or at months 0, 2, and 6. 10 μg, 30 μg, and 100 μg of each antigen were administered in the first, second, and third cohorts, respectively. The intention-to-treat population was used for safety analyses; while for immunogenicity analyses, the per-protocol population was used (children who received all scheduled vaccinations). The primary outcome was to evaluate the vaccines' safety and reactogenicity in healthy children aged between six and ten years. The secondary outcome was to measure antigen-specific serum IgG antibody levels at pre-vaccination and post-vaccination timepoints by qualified ELISAs. The trial is registered with ClinicalTrials.gov, NCT02839161, and is completed.FINDINGSBetween Jan 23 and Oct 3, 2017, 137 children were screened, of whom 76 were eligible for this trial. 60 children were recruited, and allocated to either 10 μg of the co-administered antigens (n=8 for each injection schedule), 30 μg (n=8 for each schedule), 100 μg (n=8 for each schedule), or HBV and placebo (n=6 for each schedule) in three sequential cohorts. Co-administration of the vaccines was well tolerated; the most frequent solicited adverse events were mild-to-moderate injection-site pain, observed in up to 12 (75%) of 16 participants per vaccine group, and mild headache (12 [25%] of 48) and fever (11 [23%] of 48). No vaccine-related serious adverse events were observed. Significant anti-Na-APR-1(M74) and anti-Na-GST-1 IgG levels were induced in a dose-dependent manner, with peaks seen 14 days after the third vaccinations, regardless of dose (for Na-APR-1[M74], geometric mean levels [GML]=2295·97 arbitrary units [AU] and 726·89 AU, while for Na-GST-1, GMLs=331·2 AU and 21·4 AU for the month 0, 2, and 6 and month 0, 2, and 4 schedules, respectively). The month 0, 2, and 6 schedule induced significantly higher IgG responses to both antigens (p=0·01 and p=0·04 for Na-APR-1[M74] and Na-GST-1, respectively).INTERPRETATIONCo-administration of recombinant Na-APR-1(M74) and Na-GST-1 to school-aged Gabonese children was well tolerated and induced significant IgG responses. These results justify further evaluation of this antigen combination in proof-of-concept controlled-infection and efficacy studies in hookworm-endemic areas.FUNDINGEuropean Union Seventh Framework Programme.

2024-07-01·The Lancet Infectious Diseases

A step forward in the journey towards hookworm vaccines

Article

作者: Bouchery, Tiffany ; Keiser, Jennifer

2024-07-01·Vaccine

Vaccine value profile for Hookworm

Article

作者: Periago, Victoria ; Gaspari, Erika ; Puchner, Karl Philipp ; Grobusch, Martin ; Lee, Bruce ; Diemert, David ; McCarthy, James ; Bottazzi, Maria Elena ; Hotez, Peter ; Maizels, Rick

Hookworm, a parasitic infection, retains a considerable burden of disease, affecting the most underprivileged segments of the general population in endemic countries and remains one of the leading causes of mild to severe anemia in Low and Middle Income Countries (LMICs), particularly in pregnancy and children under 5. Despite repeated large scale Preventive Chemotherapy (PC) interventions since more than 3 decades, there is broad consensus among scholars that elimination targets set in the newly launched NTD roadmap will require additional tools and interventions. Development of a vaccine could constitute a promising expansion of the existing arsenal against hookworm. Therefore, we have evaluated the biological and implementation feasibility of the vaccine development as well as the added value of such a novel tool. Based on pipeline landscaping and the current knowledge on key biological aspects of the pathogen and its interactions with the host, we found biological feasibility of development of a hookworm vaccine to be moderate. Also, our analysis on manufacturing and regulatory issues as well as potential uptake yielded moderate implementation feasibility. Modelling studies suggest a that introduction of a vaccine in parallel with ongoing integrated interventions (PC, WASH, shoe campaigns), could substantially reduce burden of disease in a cost - saving mode. Finally a set of actions are recommended that might impact positively the likelihood of timely development and introduction of a hookworm vaccine.

100 项与 Hookworm vaccine(Albert B. Sabin Vaccine Institute, Inc.) 相关的药物交易

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