Towards a vaccine forCryptococcus neoformans: principles and caveats

Abstract

In the Damage-response framework of microbial pathogenesis, infectious diseases are one outcome of a host-microorganism interaction in a susceptible host. In cryptococcal disease, damage to the host is caused by Cryptococcus neoformans virulence determinants, the nature of the host response, or both. Further, the disease may be acute or reactivated from a latent state. Hence, a vaccine for C. neoformans would need to prevent disease resulting from either acute or reactivated infection. The evidence to support the development of a vaccine for C. neoformans that induces antibody-mediated immunity is discussed herein.

Extracellular Vesicles Produced by Cryptococcus neoformans Contain Protein Components Associated with Virulence

“…The major capsular polysaccharide, glucuronoxylomannan (GXM), is released extracellularly during infection and induces a number of deleterious effects to the host, including interference with phagocytosis, inhibition of leukocyte migration to infected tissues, and modulation of cytokine production (reviewed in reference 32). It also represents a potential component for vaccines (13) and is the target of potentially therapeutic antibodies (7).…”

Of Mice and Men, Revisited: New Insights into an Ancient Molecule from Studies of Complement Activation byCryptococcus neoformans

“…Certain phenotypic variants (21) and cytokine milieus (53) induce excessive inflammatory responses to C. neoformans. Such responses could also be responsible for highly active antiretroviral therapy-or post-organ transplantation-associated immune reconstitution cryptococcosis (59,60) or that which can occur after antifungal treatment itself (16), underscoring that cryptococcosis can occur in the setting of strong as well as weak immune responses (12). Strong inflammatory responses could occur if complement and antibody deposition on the cryptococcal surface promote phagocytosis by activating both complement and Fc receptors.…”

Problems of Vaccinal Prevention of Deep Mycoses

“…Большинство вакцин на основе C. albicans и Cryptococcus neoformans в экспериментах на жи-вотных формируют защиту с помощью гуморальных антител, что подтверждается успешным использо-ванием для лечения моноклональных антител и им-мунных сывороток [17,29,30].…”