Suppressive and additive effects in protection mediated by combinations of monoclonal antibodies specific for merozoite surface protein 1 of Plasmodium yoelii

Malaria Journal

Research

Beatriz M Pernia¹  Lilian M Spencer¹  Anthony A Holder²  Gilberto Payares³  Irosoki Eslava⁴ 

[1] Department of Cell Biology, Simón Bolívar University, AP 89000, Caracas, Venezuela;Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London, UK;Institute of Experimental Biology, Central University of Venezuela, Caracas, Venezuela;School of Bioanalysis, Central University of Venezuela, Caracas, Venezuela;

关键词: Malaria;    Passive Immunization;    Malaria Vaccine;    Merozoite Surface Protein;    Challenge Infection;   

DOI  :  10.1186/1475-2875-9-46

 received in 2009-08-07, accepted in 2010-02-10,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe merozoite surface protein (MSP)-1 is a target antigen of protective immunity and a malaria vaccine candidate. The nature of this protective immune response warrants further investigation: although specific antibody is thought to play a major role, the mechanisms of protection are still unclear. Monoclonal antibodies (mAbs) specific for the C-terminus of MSP-1 from Plasmodium yoelii have been shown previously to provide protection against challenge infection when administered by passive immunization to mice. Three protective mAbs were re-examined and, in particular, the effect of combinations of antibodies on the protection provided was studied. It was found that a combination of two antibodies can either provide additive protective effects or result in a suppression of protection. In this report the importance of antibody subclass and epitope specificity in the outcome of these passive immunization experiments are discussed.MethodsThe minimum protective dose (MPD) for each mAb was determined, and then combinations of antibody at their MPD were investigated for their ability to control parasitaemia and promote survival in groups of mice. Mice were inoculated over three days with the MPD and challenged with a blood stage infection of the virulent P. yoelii 17 XL. The resultant parasitaemia was assessed daily on Giemsa-stained blood films. Following the infection the presence of MSP-1 specific antibodies in the sera was monitored, and the proliferative responses of cells in the spleen of protected mice were measured.ResultsCombining antibodies resulted in either an additive effect on protection, with reduced peak parasitaemia and better survival, or resulted in a suppression of protection over that achieved by a single antibody alone. An additive effect was observed when B6 and F5 that have the same isotype and similar fine specificity, were combined. However, a combination of mAb D3, an IgG2a, with either B6 or F5 (both IgG3) suppressed protection, an effect that may have been due to the combination of different isotypes or to the different fine specificity of the antibodies.ConclusionsThese results suggest that a combination of protective antibodies with either the same or different isotypes can produce either an additive or a suppressive effect in passive immunization. This phenomenon may be important in better understanding immunity in this experimental mouse model of malaria.

【 授权许可】

Unknown   
© Eslava et al; licensee BioMed Central Ltd. 2010. 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 cited.