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Researchers say they have located a new, more precise target for a mosquito-based vaccine to block the transmission of malaria.
The team created a 3-D crystal structure of AnAPN1, a protein found in the gut of the Anopheles mosquito that is considered essential to malaria transmission.
In studying the entire protein, the researchers found that previous incarnations of a proposed vaccine included irrelevant regions of AnAPN1.
Rhoel R. Dinglasan, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues described this work in Nature Structural & Molecular Biology.
AnAPN1 is found on the apical surface of the Anopheles gambiae midgut and is potentially a receptor for the Plasmodium parasite. As a vaccine antigen, AnAPN1 prompts antibody production, but only some of these antibodies block parasite transmission.
“This dilution of the overall antibody response to AnAPN1 is problematic,” Dr Dinglasan said. “To further improve vaccine immunogenicity at the preclinical stage, we need to immuno-focus the antibody response to only the critical, transmission-blocking regions of the protein.”
Using the Australian Synchrotron, the researchers were able to visualize the crystal structure of AnAPN1 for the first time. This allowed the team to pinpoint the binding site of AnAPN1 antibodies that can and cannot block parasite development.
“We now know much more about which parts of the AnAPN1 protein are involved in generating transmission-blocking antibodies and have a new hypothesis as to how they might work,” said Natalie Borg, PhD, of Monash University in Clayton, Victoria, Australia.
The researchers identified a particularly potent antibody, 4H5B7, and tested it in blood samples from children carrying the Plasmodium falciparum parasite. 4H5B7 exhibited “complete transmission-blocking activity” against these naturally circulating strains of P falciparum.
The team said their data indicate the mechanism underlying this activity is the recognition of a conformation-dependent epitope that is predominantly found on peptide 4, which is part of peptide 7 on domain 1 of AnAPN1.
These findings suggest that, previously, researchers were asking the immune system to target too many regions on AnAPN1, which diluted the response to the relevant regions of the protein. 
Photo courtesy of the CDC
Researchers say they have located a new, more precise target for a mosquito-based vaccine to block the transmission of malaria.
The team created a 3-D crystal structure of AnAPN1, a protein found in the gut of the Anopheles mosquito that is considered essential to malaria transmission.
In studying the entire protein, the researchers found that previous incarnations of a proposed vaccine included irrelevant regions of AnAPN1.
Rhoel R. Dinglasan, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues described this work in Nature Structural & Molecular Biology.
AnAPN1 is found on the apical surface of the Anopheles gambiae midgut and is potentially a receptor for the Plasmodium parasite. As a vaccine antigen, AnAPN1 prompts antibody production, but only some of these antibodies block parasite transmission.
“This dilution of the overall antibody response to AnAPN1 is problematic,” Dr Dinglasan said. “To further improve vaccine immunogenicity at the preclinical stage, we need to immuno-focus the antibody response to only the critical, transmission-blocking regions of the protein.”
Using the Australian Synchrotron, the researchers were able to visualize the crystal structure of AnAPN1 for the first time. This allowed the team to pinpoint the binding site of AnAPN1 antibodies that can and cannot block parasite development.
“We now know much more about which parts of the AnAPN1 protein are involved in generating transmission-blocking antibodies and have a new hypothesis as to how they might work,” said Natalie Borg, PhD, of Monash University in Clayton, Victoria, Australia.
The researchers identified a particularly potent antibody, 4H5B7, and tested it in blood samples from children carrying the Plasmodium falciparum parasite. 4H5B7 exhibited “complete transmission-blocking activity” against these naturally circulating strains of P falciparum.
The team said their data indicate the mechanism underlying this activity is the recognition of a conformation-dependent epitope that is predominantly found on peptide 4, which is part of peptide 7 on domain 1 of AnAPN1.
These findings suggest that, previously, researchers were asking the immune system to target too many regions on AnAPN1, which diluted the response to the relevant regions of the protein.
Photo courtesy of the CDC
Researchers say they have located a new, more precise target for a mosquito-based vaccine to block the transmission of malaria.
The team created a 3-D crystal structure of AnAPN1, a protein found in the gut of the Anopheles mosquito that is considered essential to malaria transmission.
In studying the entire protein, the researchers found that previous incarnations of a proposed vaccine included irrelevant regions of AnAPN1.
Rhoel R. Dinglasan, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and his colleagues described this work in Nature Structural & Molecular Biology.
AnAPN1 is found on the apical surface of the Anopheles gambiae midgut and is potentially a receptor for the Plasmodium parasite. As a vaccine antigen, AnAPN1 prompts antibody production, but only some of these antibodies block parasite transmission.
“This dilution of the overall antibody response to AnAPN1 is problematic,” Dr Dinglasan said. “To further improve vaccine immunogenicity at the preclinical stage, we need to immuno-focus the antibody response to only the critical, transmission-blocking regions of the protein.”
Using the Australian Synchrotron, the researchers were able to visualize the crystal structure of AnAPN1 for the first time. This allowed the team to pinpoint the binding site of AnAPN1 antibodies that can and cannot block parasite development.
“We now know much more about which parts of the AnAPN1 protein are involved in generating transmission-blocking antibodies and have a new hypothesis as to how they might work,” said Natalie Borg, PhD, of Monash University in Clayton, Victoria, Australia.
The researchers identified a particularly potent antibody, 4H5B7, and tested it in blood samples from children carrying the Plasmodium falciparum parasite. 4H5B7 exhibited “complete transmission-blocking activity” against these naturally circulating strains of P falciparum.
The team said their data indicate the mechanism underlying this activity is the recognition of a conformation-dependent epitope that is predominantly found on peptide 4, which is part of peptide 7 on domain 1 of AnAPN1.
These findings suggest that, previously, researchers were asking the immune system to target too many regions on AnAPN1, which diluted the response to the relevant regions of the protein.