Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies

Malaria Journal

Research

Michael P Fay¹  Jingyang Chen²  Olga Muratova²  Patrick E Duffy²  Cristina Stoyanov²  Lynn Lambert²  Sachy Orr-Gonzalez²  Jessica Hinderer²  Katie Lynn Zeleski²  Robert W Gwadz³  Thomas L Richie⁴  David Fryauff⁴  Walter R Weiss⁴  Eileen Franke Villasante⁴  Gyan Joshi⁵  Tatyana Savransky⁶  Jason H Richardson⁶  Jittawadee R Murphy⁶  Megan Dowler⁶ 

[1] NIH, NIAID, Division of Clinical Research, Biostatistics Research Branch, Bethesda, MD, USA;NIH, NIAID, The Laboratory of Malaria Immunology and Vaccinology, Rockville, MD, USA;NIH, NIAID, The Laboratory of Malaria and Vector Research, Rockville, MD, USA;Naval Medical Research Center, Silver Spring, MD, USA;SAIC-Frederick, Inc, Frederick National Laboratory for Cancer Research, 21702, Frederick, MD, USA;Walter Reed Army Institute of Research, Silver Spring, MD, USA;

关键词: Monkey;    Rhesus;    Macaca mulatta;    Plasmodium knowlesi;    Anopheles dirus;    Anopheles crascen;    Vaccine;    Methylparaben;    Mosquito;    Challenge;   

DOI  :  10.1186/1475-2875-13-215

 received in 2013-11-04, accepted in 2014-03-03,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundWhen rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. To better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was developed.MethodsSeveral species and strains of mosquitoes were tested for their ability to produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on oocyst and sporozoite numbers and mosquito mortality were documented. Methylparaben added to mosquito feed was tested to improve mosquito survival. To determine the number of bites needed to infect a monkey, animals were exposed to various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected mosquitoes were used to challenge 17 monkeys in a malaria vaccine trial, and the effect of number of infectious bites on monkey parasitaemia was documented.ResultsAnopheles dirus, Anopheles crascens, and Anopheles dirus X (a cross between the two species) produced large numbers of P. knowlesi sporozoites. Mosquito survival to day 14, when sporozoites fill the salivary glands, averaged only 32% when donor monkeys had a parasitaemia above 2%. However, when donor monkey parasitaemia was below 2%, mosquitoes survived twice as well and contained ample sporozoites in their salivary glands. Adding methylparaben to sugar solutions did not improve survival of infected mosquitoes. Plasmodium knowlesi was very infectious, with all monkeys developing blood stage infections if one or more infected mosquitoes successfully fed. There was also a dose-response, with monkeys that received higher numbers of infected mosquito bites developing malaria sooner.ConclusionsAnopheles dirus, An. crascens and a cross between these two species all were excellent vectors for P. knowlesi. High donor monkey parasitaemia was associated with poor mosquito survival. A single infected mosquito bite is likely sufficient to infect a monkey with P. knowlesi. It is possible to efficiently challenge large groups of monkeys by mosquito bite, which will be useful for P. knowlesi vaccine studies.

【 授权许可】

Unknown   
© Murphy et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.