Vaccination with Recombinant N-Terminal Domain of Als1p Improves Survival during Murine Disseminated Candidiasis by Enhancing Cell-Mediated, Not Humoral, Immunity

Abstract

Candida spp. are opportunistic fungal pathogens that are among the most common causes of nosocomial bloodstream infections. The mortality attributable to disseminated candidiasis is 40 to 50% despite antifungal therapy. Clearly, new strategies are needed to prevent this life-threatening infection. Because risk factors for disseminated candidiasis are well defined and frequently of limited duration, vaccination is an appealing prophylactic strategy. We have identified a cell surface protein, Als1p, that mediates adherence of Candida albicans to a variety of human substrates and plastic. Here we report that immunizing BALB/c mice with the recombinant N-terminal domain of Als1p (rAls1p-N) improved survival during a subsequent challenge with a lethal inoculum of C. albicans. The protective 20-g dose of rAls1p-N significantly increased Candida stimulation of Th1 splenocytes and increased in vivo delayed-type hypersensitivity. In contrast, antibody titers did not correlate with protection. Finally, the vaccine was not protective in T-cell-deficient mice but was protective in B-cell-deficient mice. These data indicate that the mechanism of action of the rAls1p-N vaccine is stimulation of cell-mediated, rather than humoral, immunity against C. albicans. The majority of efforts to date have focused on the development of passive immunization strategies to prevent or treat disseminated candidiasis. In contrast, our results provide proof of principle for vaccination with an adhesin of C. albicans and emphasize the potential for cell-mediated immune modulation as a prophylactic or therapeutic strategy against disseminated candidiasis.

The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice

“…To generate immune serum for passive immunization, normal BALB/c mice were immunized by s.c. injection of 20 μg recombinant hamster GRP78 (which is more than 98% identical to murine or human GRP78) mixed with CFA (Sigma-Aldrich) or with CFA alone mixed with PBS to generate non-immune control serum (40,41). Mice were boosted in incomplete Freund's adjuvant (IFA) 3 weeks later.…”

Anti-recurrent therapy of chronic VVC: realities and perspectives

“…Однако данная вакцина включает антигенный ма-териал ряда грибов без учета индивидуального спектра микроорганизмов конкретного пациента. Определенные успехи в лечении кандидоза связаны с разработкой вак-цин на основе моноклональных антител [14]. Иммуниза-ция рекомбинантным N-терминальным доменом белка Als1p (поверхностный протеин, обеспечивающий адгезию Candida spp.)…”

“…Иммуниза-ция рекомбинантным N-терминальным доменом белка Als1p (поверхностный протеин, обеспечивающий адгезию Candida spp.) стимулирует клеточный иммунитет [14]. Од-ним из вариантов иммунотерапии кандидоза является применение антиманнанового человеческого рекомби-нантного иммуноглобулина G1 (M1g1).…”

Advanced topical drug delivery system for the management of vaginal candidiasis

“…Recombinant ALS vaccine for VC: Ibrahim et al developed vaccine of recombinant N-terminus of Als 1p (rAls 1p) for protection of mice against disseminated and mucosal candidiasis. The vaccine enhances cell-mediated immunity rather than humoral and improves survival of mice during candidiasis (Ibrahim et al, 2005). Latter on they formulated another vaccine of recombinant N-teminus of Als 3p (rAls 3p) against disseminated and mucosal Candidiasis.…”