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So far, vaccines containing AMA1 alone have been unsuccessful in clinical trials. However, immunization with AMA1 bound with RON2L (AMA1-RON2L) induces better protection against <jats:italic>P. falciparum<\/jats:italic> malaria in <jats:italic>Aotus<\/jats:italic> monkeys. We therefore sought to determine whether combinations of RH5, RIPR, CyRPA and AMA1-RON2L antibodies improve their biological activities and sought to develop a robust method for determination of synergy or additivity in antibody combinations. Rabbit antibodies against AMA1-RON2L, RH5, RIPR or CyRPA were tested either alone or in combinations in <jats:italic>P. falciparum<\/jats:italic> growth inhibition assay to determine Bliss' and Loewe's additivities. The AMA1-RON2L\/RH5 combination consistently demonstrated an additive effect while the CyRPA\/RIPR combination showed a modest synergistic effect with Hewlett\u2019s <jats:inline-formula><jats:alternatives><jats:tex-math>$$S=1.07 \\left[95\\% \\mathrm{C}\\mathrm{I}: 1.03, 1.19\\right].$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:mrow>\n                    <mml:mi>S<\/mml:mi>\n                    <mml:mo>=<\/mml:mo>\n                    <mml:mn>1.07<\/mml:mn>\n                    <mml:mfenced>\n                      <mml:mn>95<\/mml:mn>\n                      <mml:mo>%<\/mml:mo>\n                      <mml:mi>C<\/mml:mi>\n                      <mml:mi>I<\/mml:mi>\n                      <mml:mo>:<\/mml:mo>\n                      <mml:mn>1.03<\/mml:mn>\n                      <mml:mo>,<\/mml:mo>\n                      <mml:mn>1.19<\/mml:mn>\n                    <\/mml:mfenced>\n                    <mml:mo>.<\/mml:mo>\n                  <\/mml:mrow>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula> Additionally, we provide a publicly-available, online tool to aid researchers in analyzing and planning their own synergy experiments. This study supports future blood-stage vaccine development by providing a solid methodology to evaluate additive and\/or synergistic (or antagonistic) effect of vaccine-induced antibodies.<\/jats:p>","DOI":"10.1038\/s41598-020-67877-8","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T10:04:22Z","timestamp":1594893862000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations"],"prefix":"10.1038","volume":"10","author":[{"given":"Yvonne","family":"Azasi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon K.","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ababacar","family":"Diouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Dabbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Yusuf","family":"Mian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Narum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole A.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Gaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Draper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Fay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis H.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutoyo","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"67877_CR1","unstructured":"World Health Organization. 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