111. Investigating the longevity of Plasmodium falciparum-specific IgG responses in absence of infection: a longitudinal study in Mali
Session: Oral Abstract Session: Global Health
Thursday, October 8, 2015: 10:30 AM
Room: 32--ABC

Background: Studies examining longevity of Plasmodium falciparum specific antibody responses are often complicated by variable or unknown exposure to P. falciparum infection during the study period, and have been limited by a small number of malaria antigens available for analysis. Here we sought to overcome these limitations through a P. falciparum protein microarray to estimate antibody longevity by age and antigen over the six-month dry season in Mali—a period when malaria transmission falls to near zero.

Methods: We focused on 140 children aged 2-10 years, when a transition from susceptibility to immunity to clinical malaria is expected, who were PCR negative for P. falciparum infection the beginning and end of the 2012 dry season in Kalifabougou, Mali. Plasma samples collected before and after the dry season were probed against a P. falciparum protein microarray, and IgG reactivity to these antigens was measured (Fig 1). We then identified antigens with associated IgG reactivity with the highest probability of seroreversion (by generalized estimating equation (GEE) with serostatus as a factor) as short-lived, and those with the lowest probability of decreasing (by GEE with IgG reactivity as a covariate) as long-lived.

Results: Three antigens were identified from the short-lived group (merozoite surface protein 1, heat shock protein 40, and Mauer's cleft two transmembrane protein, p<0.05, Fig 2A) and from the long-lived group (gametocytogenesis-implicated protein, HAD superfamily protein, and conserved Plasmodium protein PF3D7_0717200, p<0.05, Fig 2B) as potential serologic targets of respective recent and remote P. falciparum exposure in population-based serologic surveys. These antigens were all associated with antibody seroprevalence of >80% at the start of the dry season.

Conclusion: We have identified antigens eliciting short and long-lived P. falciparum specific antibody responses in children 2-10 years of age that with further validation may serve as tools in malaria surveillance and control programs.

Fig 1 Study design

Description: Macintosh HD:Users:liuew:Dropbox:fellowship:IDWeek:flowchart.png

Fig 2 Changes in IgG reactivity in 140 children to short & long-lived antigen (A& B, respectively). Each line connects measured reactivity at the start and end of the dry season by age for a child. Blue or red color indicates a decrease or increase in reactivity, respectively.

A

B

Eugene Liu, MD1, Chiung-Yu Huang, PhD2, Jeff Skinner, M.S.3, Aarti Jain, MS4, Aissata Ongoiba, M.D.5, Shanping Li, M.S.3, Safiatou Doumbo, M.D.5, Didier Doumtabe, Pharm.D.5, Younoussou Kone, M.D.5, Aboudramane Bathily, M.D.5, Jules Sangala, M.D.5, Ogobara K. Doumbo, M.D., Ph.D.5, Kassoum Kayentao, M.D., M.P.H.5, Boubacar Traore, Pharm.D., Ph.D.5, Philip Felgner, Ph.D.6 and Peter D. Crompton, M.D., M.P.H.3, (1)NIH, Rockville, MD, (2)Division of Biostatistics and Bioinformatics Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University, Baltimore, MD, (3)Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, (4)Dept. of Medicine - Div. of Infectious Diseases, University of California, Irvine, Irvine, CA, (5)Mali International Center of Excellence in Research, Bamako, Mali, (6)Medicine/Infectious Diseases, University of California, Irvine, Irvine, CA

Disclosures:

E. Liu, None

C. Y. Huang, None

J. Skinner, None

A. Jain, None

A. Ongoiba, None

S. Li, None

S. Doumbo, None

D. Doumtabe, None

Y. Kone, None

A. Bathily, None

J. Sangala, None

O. K. Doumbo, None

K. Kayentao, None

B. Traore, None

P. Felgner, Antigen Discovery, Inc.: Scientific Advisor and Shareholder , Consulting fee

P. D. Crompton, None

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