high antibody titer against apical membrane antigen-1 is required to protect against malaria in the aotus model高抗体效价与顶端膜antigen-1汇合模型中需要防止疟疾.pdfVIP

High Antibody Titer against Apical Membrane Antigen-1 Is Required to Protect against Malaria in the Aotus Model 1 2 2 4 4 Sheetij Dutta *, JoAnn S. Sullivan , Katharine K. Grady , J. David Haynes , Jack Komisar , Adrian H. 1 3 3 4 4 2 Batchelor , Lorraine Soisson , Carter L. Diggs , D. Gray Heppner , David E. Lanar , William E. Collins , John W. Barnwell2* 1 Department of Epitope Mapping, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America, 2 Malaria Branch, Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 3 Malaria Vaccine Development Program, United States Agency for International Development, Washington, D. C., United States of America, 4 Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America Abstract A Plasmodium falciparum 3D7 strain Apical Membrane Antigen-1 (AMA1) vaccine, formulated with AS02A adjuvant, slowed parasite growth in a recent Phase 1/2a trial, however sterile protection was not observed. We tested this AS02A, and a Montanide ISA720 (ISA) formulation of 3D7 AMA1 in Aotus monkeys. The 3D7 parasite does not invade Aotus erythrocytes, hence two heterologous strains, FCH/4 and FVO, were used for challenge, FCH/4 AMA1 being more homologous to 3D7 than FVO AMA1. Following three vaccinations, the monkeys were challenged with 50,000 FCH/4 or 10,000 FVO parasites. Three of the six animals in the AMA+ISA group were protected against FCH/4 challenge. One monkey d