Delayed Time to Cryptosporidiosis in Bangladeshi Children is Associated with Greater Fecal IgA against Two Sporozoite-Expressed Antigens

Abstract

Cryptosporidiosis is common in early childhood, and both diarrheal and subclinical infections are associated with adverse developmental outcomes. Improved therapeutic medications may help reduce the burden of cryptosporidial diarrhea; however, an effective vaccine would be better able to prevent the detrimental impact of both diarrheal and subclinical disease. A more complete understanding of naturally occurring immunity may further inform strategies to develop an effective vaccine. In this prospective cohort study of Bangladeshi children, greater fecal IgA at 12 months, but not plasma IgG, directed against two sporozoite-expressed, immunodominant and vaccine candidate antigens was associated with delayed time to subsequent cryptosporidiosis to 3 years of life. These findings extend prior work and further support the role of mucosal antibody responses in naturally developing protective immunity to Cryptosporidium.

Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition

“…Children with high levels of fecal anti-Cp23 IgA were regarded as being previously exposed to the Cryptosporidium parasite even if the parasite had been missed during surveillance for sub-clinical infections. In previous work it was shown that even if Cryptosporidium DNA had not been identified high levels (> mean value) of fecal anti-Cp23 IgA at one year of age was associated with an increased resistance to cryptosporidiosis through age three [ 14 , 20 ]. In children with high fecal anti-Cp23 IgA there was an increase in the number of days until a child was reinfected and a subsequent decrease in the proportion of children in this group reinfected during years 2-3 (in children with high fecal anti-Cp23 IgA 77.8% were reinfected versus 92.2%)…”

“…To this end, a community-based prospective cohort study of cryptosporidiosis was begun in 2014 [13]. The study subjects, born in an urban slum in Dhaka, Bangladesh were enrolled during the first week of life [13][14][15]. In humans and in animal models vaccination or prior infection resulted in partial protection against reinfection [16][17][18][19].…”

Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition

“…(Slope: -0.294 ± 0.05; R squared value: 0.08; Significance p < 0.0001). C) Relationship of all-cause diarrhea with HAZ at 3 years of age (p = NS).Mucosal IgA against the sporozoite Cp23 protein was associated with protection from growth falteringIn previous work it was shown in this cohort that a high level (> mean value) of fecal anti-Cp23IgA at one year of age was associated with an increased resistance to cryptosporidiosis through age three[14,20]. Here we additionally discovered that children with high levels (upper 50 th percentile) of fecal anti-Cp23 IgA at one year of age were protected from growth faltering through year 3(Fig 6).…”

“…To this end, a community-based prospective cohort study of cryptosporidiosis was begun in 2014 [13]. The study subjects were born in an urban slum in Dhaka, Bangladesh and enrolled during the first week of life [13][14][15]. In humans and in animal models vaccination or prior infection resulted in partial protection against reinfection [16][17][18][19].…”

Development of Two Mouse Models for Vaccine Evaluation against Cryptosporidiosis

“…High levels of mucosal Cryptosporidium Cp23-specific IgA were reported to delay parasite reinfection in young children and to protect them from diarrhea-associated growth faltering. This partial immunity is believed to be associated with acquired mucosal IgA ( 31 , 32 ). Similarly, oral immunization with live C. parvum oocysts stimulated Cryptosporidium- specific IgA in feces and mice became more resistant to a secondary challenge even after treatment with IFN-γ-neutralizing MAb.…”