Progress in the development of a recombinant vaccine for human hookworm disease: The Human Hookworm Vaccine Initiative

Hotez, Peter J.; Zhan, Bin; Bethony, Jeffrey M.; Loukas, Alex; Williamson, Angela; Goud, Gaddam Narsa; Hawdon, John M.; Dobardzic, Azra; Dobardzic, R.; Ghosh, Kashinath; Bottazzi, María Elena; Méndez, Susana; Zook, Bernard C.; Yan, Weili; L, Sen; Essiet-Gibson, Idong; Chung-Debose, Sophia; Shuhua, Xiao; Knox, David P.; Meagher, Michael M.; İnan, Mehmet; Correa-Oliveira, Rodrigo; Vilk, Paul; Shepherd, Herman R; Brandt, Walter E.; Russell, Philip K.

doi:10.1016/s0020-7519(03)00158-9

Cited by 130 publications

(99 citation statements)

References 98 publications

(74 reference statements)

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“…Our results also confirm that the mechanisms of action of the two larval proteins are different, since only ASP-2 promoted neutrophil migration. Na-ASP-2 has been selected as a vaccine candidate based on human immuno-epidemiologic studies and laboratory animal vaccine trials Goud et al, 2004;Hotez et al, 2003;Mendez et al, 2005). In order to clarify the role of Na-ASP-2 as a functional vaccine, and in an attempt to unravel its function, structural studies were carried out .…”

Section: Discussionmentioning

confidence: 99%

“…Hookworm proteins involved in tissue invasion are particularly good candidate antigens for the development of vaccines and drugs (Hotez et al, 2003). On the basis of in vitro data, animal trials and human epidemiological studies Goud et al, 2004;Hotez et al, 2003;Mendez et al, 2005), the L3-secreted N. americanus ASP-2 (Na-ASP-2) was selected as a vaccine antigen to undergo further development .…”

Section: Introductionmentioning

confidence: 99%

“…On the basis of in vitro data, animal trials and human epidemiological studies Goud et al, 2004;Hotez et al, 2003;Mendez et al, 2005), the L3-secreted N. americanus ASP-2 (Na-ASP-2) was selected as a vaccine antigen to undergo further development . As mentioned above, ASP-2 is released by the L3 after invading the host and it is likely to play a role in the transition to parasitism (Hotez et al, 2003). Since the function of ASP-2 is currently unknown, structural studies were initiated to clarify the role of Na-ASP-2 as a functional vaccine.…”

Section: Introductionmentioning

confidence: 99%

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Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Bower¹,

Constant²,

Méndez³

2008

Experimental Parasitology

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The L3-secreted Ancylostoma Secreted Protein-2 from the human hookworm Necator americanus (Na-ASP-2) has been selected as a candidate vaccine antigen in anticipation of clinical trials. Its crystal structure revealed that Na-ASP-2 has structural and charge similarities to CC-chemokines, suggesting that it might act as a chemokine mimic when released by the infective larvae during tissue migration. Using the air pouch model of acute inflammation, we found that Na-ASP-2 induced a significant leukocyte influx to the skin pouch, mostly comprised of neutrophils (60%) and monocytes (30%) that was transient and resolved in 24 h. Other hookworm larval proteins did not cause any inflammatory leukocytes to migrate into air pouches. In vitro chemotaxis assays confirmed our results and demonstrated that leukocyte migration was a direct effect of Na-ASP-2 exposure and not caused by other molecules released by host cells in the inflammatory microenvironment or by the expression vector.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Bower¹,

Constant²,

Méndez³

2008

Experimental Parasitology

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“…Hookworms account for one third of all nematode infections. Efforts to develop effective vaccines against these parasites have not been successful (1). In general, helminths induce a strong type 2 immune response, which is characterized by high IgE levels and increased numbers of Th2 cells, mast cells, eosinophils, and basophils.…”

mentioning

confidence: 99%

Basophils Protect against Reinfection with Hookworms Independently of Mast Cells and Memory Th2 Cells

Ohnmacht¹,

Voehringer²

2009

The Journal of Immunology

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Hookworms infect several hundred million people worldwide, causing malnutrition, anemia, and growth retardation. Infections generally result in a strong type 2 immune response, but the effector mechanisms that mediate worm expulsion remain poorly characterized. In this study, we determined the role of mast cells and basophils in protective immunity against the murine hookworm, Nippostrongylus Brasiliensis, during primary and secondary infection. Mast cell–deficient c-KitW-sh mice had lower serum IgE levels compared with wild-type mice under steady-state conditions and after N. brasiliensis infection. Worm expulsion was delayed during primary but not during secondary infection of c-KitW-sh mice, even in the absence of CD4 T cells. However, protective immunity was lost when basophils were depleted before reinfection of c-KitW-sh mice. We conclude that basophils play a crucial role for worm expulsion during a memory type 2 immune response independently of mast cells and memory Th2 cells.

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“…Recombinant antigen vaccines against helminth infections have been tested with limited success (8,28,35,36), which in part may be due to the altered conformation and/or glycosylation of the recombinant antigens. An alternative vaccination approach has been to immunize mice with DNA, where the protein product is produced in vivo from the plasmid DNA.…”

mentioning

confidence: 99%

DNA Immunization with Na ⁺ -K ⁺ ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

et al. 2005

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Strongyloides stercoralis causes chronic asymptomatic infections which can be maintained in the human host for many decades. Identification and treatment of S. stercoralis-infected individuals is required because immunosuppression can lead to fatal hyperinfection. In this study, human immunoglobulin G (IgG) that had previously been shown to transfer protective immunity to mice was used to identify potential protective antigens. Three antigens or genes from S. stercoralis larvae were identified as tropomyosin (Sstmy-1), Na ؉ -K ؉ ATPase (Sseat-6), and LEC-5 (Sslec-5). The genes were cloned into plasmids for DNA immunization, and mice were immunized intradermally with the three plasmids individually in combination with a plasmid containing murine granulocyte-macrophage colony-stimulating factor. Only Na ؉ -K

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Progress in the development of a recombinant vaccine for human hookworm disease: The Human Hookworm Vaccine Initiative

Cited by 130 publications

References 98 publications

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Basophils Protect against Reinfection with Hookworms Independently of Mast Cells and Memory Th2 Cells

DNA Immunization with Na ⁺ -K ⁺ ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

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Progress in the development of a recombinant vaccine for human hookworm disease: The Human Hookworm Vaccine Initiative

Cited by 130 publications

References 98 publications

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Necator americanus: The Na-ASP-2 protein secreted by the infective larvae induces neutrophil recruitment in vivo and in vitro

Basophils Protect against Reinfection with Hookworms Independently of Mast Cells and Memory Th2 Cells

DNA Immunization with Na + -K + ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

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Product

Resources

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DNA Immunization with Na ⁺ -K ⁺ ATPase ( Sseat-6 ) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice