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 6

gp60 Genotype immune response.

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gp60 Genotype immune response. (A) Cartoon illustrating the proteins en...
(A) Cartoon illustrating the proteins encoded by the gp60 gene. (B and C) Heat maps showing the intensity and breadth of the IgA (B) and IgG (C) antibody responses to the polymorphic region of the Gp40 protein. The different alleles of the peptide encoded by the gp60 allele (columns) and the signal obtained when using the plasma with antibodies raised in response to infection of parasite with different gp60 genotypes (rows). Lines at the top of each heat map indicate the protein type and on the side the genotype of the infecting parasite. Parasite genotypes: rows 1–8: IaA18R3; 9: IaA19R3; 10–16: IaA25R3; 17–20: IbA9G3R2; 21–29: IdA15G1; 30: IfA13G1; 31–34: C. parvum IIdA15G1R1. Protein alleles: columns A: IaA27R3, B: IaA26R3, C: IaA25R3, D: IaA22R3, E: IaA19R3 F: IaA18R3, G: IbA9G3R2, H: IdA14G1, I: IdA15G1, J: IeA11G3T3, K: IfA13G1, L: IfA16G1, M: IIcA5G3a N: IIdA13G1. Side panels show the intensity scale for the amount of antibody binding to alleles expressed by IVTT and spotted on the array. Antibody binding to the purified recombinant relatively conserved Cp17 peptide was included on the array as a positive control. Its signal intensity was higher than that of the IVTT values.