Malaria infection by sporozoite challenge induces high functional antibody titres against blood stage antigens after a DNA prime, poxvirus boost vaccination strategy in Rhesus macaques

Malaria Journal

Research

Clemens HM Kocken¹  Edmond J Remarque¹  Alan W Thomas¹  Bart W Faber¹  Muzamil Mahdi Abdel Hamid²  Ayman A Hussain³  Ibrahim M El Hassan⁴  David L Narum⁵  Walter R Weiss⁶ 

[1] Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands;Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands;Institute of Endemic Diseases, University of Khartoum, Sudan;Institute of Endemic Diseases, University of Khartoum, Sudan;Institute of Endemic Diseases, University of Khartoum, Sudan;Faculty of Medicine, Jazan University, Kingdom of Saudi Arabia;Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, USA;Naval Medical Research Centre, Silver Spring, Maryland, USA;

关键词: Malaria;    Malaria Vaccine;    Protected Animal;    Parasite Growth;    Growth Inhibition Assay;   

DOI  :  10.1186/1475-2875-10-29

 received in 2010-11-03, accepted in 2011-02-08,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundA DNA prime, poxvirus (COPAK) boost vaccination regime with four antigens, i.e. a combination of two Plasmodium knowlesi sporozoite (csp/ssp2) and two blood stage (ama1/msp142) genes, leads to self-limited parasitaemia in 60% of rhesus monkeys and survival from an otherwise lethal infection with P. knowlesi. In the present study, the role of the blood stage antigens in protection was studied in depth, focusing on antibody formation against the blood stage antigens and the functionality thereof.MethodsRhesus macaques were immunized with the four-component vaccine and subsequently challenged i.v. with 100 P. knowlesi sporozoites. During immunization and challenge, antibody titres against the two blood stage antigens were determined, as well as the in vitro growth inhibition capacity of those antibodies. Antigen reversal experiments were performed to determine the relative contribution of antibodies against each of the two blood stage antigens to the inhibition.ResultsAfter vaccination, PkAMA1 and PkMSP119 antibody titres in vaccinated animals were low, which was reflected in low levels of inhibition by these antibodies as determined by in vitro inhibition assays. Interestingly, after sporozoite challenge antibody titres against blood stage antigens were boosted over 30-fold in both protected and not protected animals. The in vitro inhibition levels increased to high levels (median inhibitions of 59% and 56% at 6 mg/mL total IgG, respectively). As growth inhibition levels were not significantly different between protected and not protected animals, the ability to control infection appeared cannot be explained by GIA levels. Judged by in vitro antigen reversal growth inhibition assays, over 85% of the inhibitory activity of these antibodies was directed against PkAMA1.ConclusionsThis is the first report that demonstrates that a DNA prime/poxvirus boost vaccination regimen induces low levels of malaria parasite growth inhibitory antibodies, which are boosted to high levels upon challenge. No association could, however, be established between the levels of inhibitory capacity in vitro and protection, either after vaccination or after challenge.

【 授权许可】

Unknown   
© Abdel Hamid et al; licensee BioMed Central Ltd. 2011. 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.