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ANTIBODY RECOGNITION OF HETEROLOGOUS VARIANT SURFACE ANTIGENS AFTER A SINGLE PLASMODIUM FALCIPARUM INFECTION IN PREVIOUSLY NAÏVE ADULTS

Antibodies to variant surface antigens (VSA) including Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) have been associated with protective antimalarial immunity that appears to be variant-specific. This study of adult returned travelers with a single acute P. falciparum infection investigated whether a primary antibody response includes IgG specific for heterologous VSA. We found that 11 of 14 patients had IgG reactive with up to six P. falciparum lines expressing different heterologous PfEMP1 variants, measured by flow cytometry (reactivity greater than two times the mean of the negative control sera was defined as "positive"), with high reactivity (greater than four times the mean of the negative controls) detected in three patients. The dominant variant(s) recognized differed between seropositive individuals. Despite previous evidence that antibody responses to heterologous VSA are short-lived, seven patients had detectable IgG at > 20 weeks post-infection. Together these data suggest that a single P. falciparum infection can be sufficient to induce antibodies reactive with several PfEMP1 variants, although the repertoire of target epitopes they recognize may still be restricted.

Received October 18, 2006. Accepted for publication January 11, 2007.

Acknowledgments: The authors thank the individuals who participated in this study.

Financial Support: This work was funded by the National Health and Medical Research Council of Australia. S.R.E. received an Early Career Researcher grant from The University of Melbourne.

^* Address correspondence to Salenna R. Elliott, Royal Melbourne Hospital, Parkville, Vic, 3050, Victoria, Australia. E-mail: salenna{at}unimelb.edu.au, salennaelliott{at}yahoo.com

Authors’ addresses: Salenna R. Elliott, Paul D. Payne, Michael F. Duffy, Timothy J. Byrne, Stephen J. Rogerson, and Graham V. Brown, Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Vic, 3050, Australia, Telephone: +61 3 83446252, Fax: +61 3 93471863, E-mails: salenna{at}unimelb.edu.au, ppayne{at}unimelb.edu.au, mduffy{at}unimelb.edu.au, tjbyrne{at}unimelb.edu.au, sroger{at}unimelb.edu.au, and gvb{at}unimelb.edu.au. Wai-Hong Tham, Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Vic, 3050, Australia, and present address: The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, 3050, Australia, E-mail: tham{at}wehi.edu.au. Damon P. Eisen, Queensland Institute of Medical Research, Herston, Qld, 4029, Australia, and present address: Victorian Infectious Diseases Service, Royal Melbourne Hospital, Vic, 3050, Australia, E-mail: Damon.Eisen{at}mh.org.au.

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