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Specific Cryptosporidium antigens associate with reinfection immunity and protection from cryptosporidiosis
Carol A. Gilchrist, … , Rashidul Haque, William A. Petri Jr.
Carol A. Gilchrist, … , Rashidul Haque, William A. Petri Jr.
Published June 22, 2023
Citation Information: J Clin Invest. 2023;133(16):e166814. https://doi.org/10.1172/JCI166814.
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Research Article Immunology Infectious disease Article has an altmetric score of 7

Specific Cryptosporidium antigens associate with reinfection immunity and protection from cryptosporidiosis

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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 5

Children with antibodies that targeted the C. hominis peptides encoded by the gp60 gene and Cp23 protein were associated with protection from reinfection.

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Children with antibodies that targeted the C. hominis peptides encoded b...
In the protein array data, IgA and IgG antibodies against the protein encoded by the C. hominis gp60 gene (Chro.60183) and IgG against Cp23 (Chro.40414) were associated with a delay in Cryptosporidium reinfection among children with a qPCR-verified Cryptosporidium infection during the first year of life (A, C, and E) or among all children in the study (B, D, and F). The X-axis shows days after the end of year 1 (when the assayed plasma samples were collected). The Y-axis shows the proportion of children who remained uninfected. Red lines represent children seronegative for the antigen, and blue lines represent seropositive children. The Kaplan-Meier curves show the probability of survival free of Cryptosporidium species, and the tables below the graphs indicate the number of children in the seropositive or seronegative categories at select time points. (A and B) IgG against Gp60 (Chro.60183). (C and D) IgA against Gp60 (Chro.60183). (E and F) IgG against Cp23 (Chro.40414). Hazard ratios (HR), confidence intervals, and P values were calculated using multivariable Cox proportional hazards models.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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