Antibody Response to Cryptococcus neoformans Proteins in Rodents and Humans

Abstract

The prevalence and specificity of serum antibodies toCryptococcus neoformans proteins was studied in mice and rats with experimental infection, in individuals with or without a history of potential laboratory exposure to C. neoformans, human immunodeficiency virus (HIV)-positive individuals who developed cryptococcosis, in matched samples from HIV-positive individuals who did not develop cryptococcosis, and in HIV-negative individuals. Rodents had little or no serum antibody reactive with C. neoformans proteins prior to infection. The intensity and specificity of the rodent antibody response were dependent on the species, the mouse strain, and the viability of the inoculum. All humans had serum antibodies reactive with C. neoformans proteins regardless of the potential exposure, the HIV infection status, or the subsequent development of cryptococcosis. Our results indicate (i) a high prevalence of antibodies reactive with C. neoformansproteins in the sera of rodents after cryptococcal infection and in humans with or without HIV infection; (ii) qualitative and quantitative differences in the antibody profiles of HIV-positive individuals; and (iii) similarities and differences between humans, mice, and rats with respect to the specificity of the antibodies reactive with C. neoformans proteins. The results are consistent with the view that C. neoformans infections are common in human populations, and the results have implications for the development of vaccination strategies against cryptococcosis.

Towards a vaccine forCryptococcus neoformans: principles and caveats

“…Fleuridor et al (1999) showed that GXM-reactive IgG levels increased among HIV-infected subjects as CD4 1 Tcell counts declined. Together with data from other studies showing higher levels of GXM-or C. neoformans proteinreactive IgG among HIV-infected subjects Chen et al, 1999;Subramaniam et al, 2005), these observations suggest such antibodies could have been elicited by a new infection and/or the reactivation of C. neoformans. Further, high levels of GXM-reactive IgG could be disease-enhancing, perhaps as a clinical correlate of the prozone-like phenomenon observed in mouse models, whereby high amounts of antibody abrogate successful AMI (Taborda & Casadevall, 2001;Taborda et al, 2003;Maitta et al, 2004a).…”

Cryptococcosis‐related deaths and associated medical conditions in the United States, 2000–2010

“…7 Serological studies indicate that latent C. neoformans exposure is widespread in humans and symptomatic disease is often a reactivation of latent infection rather than a primary infection. [8][9][10] This pathway to clinical disease often contributes to its underdetection and presents challenges to prevention. Although much has been described about the burden of Cryptococcus infection in the presence of HIV, 11 less is known about this infection in other immunocompromised states or among seemingly healthy individuals.…”

Detection of IgM and IgG antibodies to Cryptococcus neoformans proteins in blood donors and HIV patients with active cryptococcosis

“…5,6 Several studies reported the presence of serological response of humans to C. neoformans protein antigens. [7][8][9][10] Chen et al [7] reported that all humans had serum antibodies reactive with C. neoformans proteins regardless of the potential exposure, the human immunodeficiency virus (HIV) infection status or the subsequent development of cryptococcosis. Goldman et al [9] reported that sera from children of 1.1-2 years old demonstrated minimal reactivity to C. neoformans proteins, whereas majority of sera from children of >2 years old recognized many ( ‡6) C. neoformans proteins.…”