Armistead Jennifer S, Morlais Isabelle, Mathias Derrick K, Jardim Juliette G, Joy Jaimy, Fridman Arthur, Finnefrock Adam C, Bagchi Ansu, Plebanski Magdalena, Scorpio Diana G, Churcher Thomas S, Borg Natalie A, Sattabongkot Jetsumon, Dinglasan Rhoel R
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health and the Malaria Research Institute, Baltimore, Maryland, USA.
Infect Immun. 2014 Feb;82(2):818-29. doi: 10.1128/IAI.01222-13. Epub 2013 Dec 9.
Malaria transmission-blocking vaccines (TBVs) represent a promising approach for the elimination and eradication of this disease. AnAPN1 is a lead TBV candidate that targets a surface antigen on the midgut of the obligate vector of the Plasmodium parasite, the Anopheles mosquito. In this study, we demonstrated that antibodies targeting AnAPN1 block transmission of Plasmodium falciparum and Plasmodium vivax across distantly related anopheline species in countries to which malaria is endemic. Using a biochemical and immunological approach, we determined that the mechanism of action for this phenomenon stems from antibody recognition of a single protective epitope on AnAPN1, which we found to be immunogenic in murine and nonhuman primate models and highly conserved among anophelines. These data indicate that AnAPN1 meets the established target product profile for TBVs and suggest a potential key role for an AnAPN1-based panmalaria TBV in the effort to eradicate malaria.
疟疾传播阻断疫苗（TBVs）是消除和根除该疾病的一种有前景的方法。AnAPN1是一种主要的TBV候选物，其靶向疟原虫专性传播媒介按蚊中肠的一种表面抗原。在本研究中，我们证明，靶向AnAPN1的抗体可阻断恶性疟原虫和间日疟原虫在疟疾流行国家中亲缘关系较远的按蚊种类间的传播。通过生化和免疫学方法，我们确定了这一现象的作用机制源于抗体对AnAPN1上单个保护性表位的识别，我们发现该表位在小鼠和非人类灵长类动物模型中具有免疫原性，且在按蚊中高度保守。这些数据表明，AnAPN1符合TBVs既定的目标产品特征，并提示基于AnAPN1的泛疟疾TBV在根除疟疾的努力中可能发挥关键作用。
