Specific Cryptosporidium antigens associate with reinfection immunity and protection from cryptosporidiosis
Carol A. Gilchrist, Joseph J. Campo, Jozelyn V. Pablo, Jennie Z. Ma, Andy Teng, Amit Oberai, Adam D. Shandling, Masud Alam, Mamun Kabir, A.S.G. Faruque, Rashidul Haque, William A. Petri Jr.
Carol A. Gilchrist, Joseph J. Campo, Jozelyn V. Pablo, Jennie Z. Ma, Andy Teng, Amit Oberai, Adam D. Shandling, Masud Alam, Mamun Kabir, A.S.G. Faruque, Rashidul Haque, William A. Petri Jr.
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Research Article Immunology Infectious disease

Specific Cryptosporidium antigens associate with reinfection immunity and protection from cryptosporidiosis

Abstract

There is no vaccine to protect from cryptosporidiosis, a leading cause of diarrhea in infants in low- and middle-income countries. Here, we comprehensively identified parasite antigens associated with protection from reinfection. A Cryptosporidium protein microarray was constructed by in vitro transcription and translation of 1,761 C. parvum, C. hominis, or C. meleagridis antigens, including proteins with a signal peptide and/or a transmembrane domain. Plasma IgG and/or IgA from Bangladeshi children longitudinally followed for cryptosporidiosis from birth to 3 years of age allowed for identification of 233 seroreactive proteins. Seven of these were associated with protection from reinfection. These included Cp23, Cp17, Gp900, and 4 additional antigens — CpSMP1, CpMuc8, CpCorA and CpCCDC1. Infection in the first year of life, however, often resulted in no detectable antigen-specific antibody response, and antibody responses, when detected, were specific to the infecting parasite genotype and decayed in the months after infection. In conclusion, humoral immune responses against specific parasite antigens were associated with acquired immunity. While antibody decay over time and parasite genotype-specificity may limit natural immunity, this work serves as a foundation for antigen selection for vaccine design.

Authors

Carol A. Gilchrist, Joseph J. Campo, Jozelyn V. Pablo, Jennie Z. Ma, Andy Teng, Amit Oberai, Adam D. Shandling, Masud Alam, Mamun Kabir, A.S.G. Faruque, Rashidul Haque, William A. Petri Jr.

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Figure 4

The breadth of the anti-Cryptosporidium immune response was not correlated with protection from infection.

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The breadth of the anti-Cryptosporidium immune response was not correlat...
(A) Split violin plot of antibody breadth in plasma among the 100 most-reactive antigens (Y-axis) for each isotype (X-axis) is shown for the comparison between children that had no stool samples (diarrheal or surveillance) qPCR+ for Cryptosporidium parasites (purple) and children who had a verified Cryptosporidium infection (green). (B) Data is shown from one year old infants who had prior qPCR-confirmed Cryptosporidium infections (“Yr0-1 qPCR+”) that were subsequently uninfected (blue) or reinfected (orange) during the next 2 years. (C) Data is shown from 1-year-old infants that included both the immunologically naive infants with no prior Cryptosporidium infections detected by qPCR in stool samples (diarrheal or surveillance) as well as those with qPCR+ stool samples during the first year of life. Medians and quartiles are indicated by horizontal lines in each split violin. Significant P values from Wilcoxon’s rank sum tests are shown above violins.