PMID- 22553959 OWN - NLM STAT- MEDLINE DCOM- 20120910 LR - 20181201 IS - 1029-2330 (Electronic) IS - 1026-7158 (Linking) VI - 20 IP - 5 DP - 2012 Jun TI - Vaccine potential of cytosolic proteins loaded fibrin microspheres of Cryptococcus neoformans in BALB/c mice. PG - 453-66 LID - 10.3109/1061186X.2012.685474 [doi] AB - Cryptococcosis is a leading mycological cause of mortality among immunologically compromised individuals. In order to develop an effective vaccine against Cryptococcus neoformans, the cytosolic proteins (Cp) of the pathogen have been used as an antigen in combination with different formulations. In the present study, we have demonstrated that Cp encapsulated poly-lactide co-glycolide (PLGA) microsphere further co-encapsulated into the biocompatible fibrin cross-linked plasma beads (Fib-PLGA-Cp) mediated cytosolic delivery elicited strong immune response in the BALB/c mice. In contrast, other formulations of Cp failed to impart significant level of protection. The immune response, involved with Fib-PLGA-Cp protection, appear to interact with the target cells by both endocytosis as well as membrane fusion mode, thus helping in the activation of both CD4(+) and CD8(+) T-cells. Analysis of cytokine profiles in immunized animals revealed that the protective response was associated with the Th1/Th2 polarization in favor of type-1 cytokine [interferons (IFN)-gamma and interleukin (IL)-2] cells. Furthermore, vaccination with Fib-PLGA-Cp elicited high immunoglobulin (Ig) G(l) and IgG(2a) isotype response; successfully cleared fungal burden in vital organs and also increased the survival rate of immunized animals. Altogether the present study is a clear indicative of the possible use of fibrin microsphere-based targeted delivery of cytosolic proteins to induce protective immune responses against experimental murine cryptococcosis. FAU - Khan, Azmat Ali AU - Khan AA AD - Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India. azmatbiotech@gmail.com FAU - Jabeen, Mumtaz AU - Jabeen M FAU - Chauhan, Arun AU - Chauhan A FAU - Owais, Mohammad AU - Owais M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120504 PL - England TA - J Drug Target JT - Journal of drug targeting JID - 9312476 RN - 0 (Antigens, Fungal) RN - 0 (Cytokines) RN - 0 (Fungal Proteins) RN - 0 (Fungal Vaccines) RN - 0 (Immunoglobulin G) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 9001-31-4 (Fibrin) SB - IM MH - Animals MH - Antigens, Fungal/immunology MH - Cryptococcosis/immunology/*prevention & control MH - Cryptococcus neoformans/*isolation & purification MH - Cytokines/immunology MH - Cytosol/metabolism MH - Disease Models, Animal MH - Endocytosis/immunology MH - Female MH - Fibrin/chemistry MH - Fungal Proteins/*immunology MH - Fungal Vaccines/*immunology MH - Immunoglobulin G/immunology MH - Lactic Acid/chemistry MH - Mice MH - Mice, Inbred BALB C MH - Microspheres MH - Polyglycolic Acid/chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Survival Rate EDAT- 2012/05/05 06:00 MHDA- 2012/09/11 06:00 CRDT- 2012/05/05 06:00 PHST- 2012/05/05 06:00 [entrez] PHST- 2012/05/05 06:00 [pubmed] PHST- 2012/09/11 06:00 [medline] AID - 10.3109/1061186X.2012.685474 [doi] PST - ppublish SO - J Drug Target. 2012 Jun;20(5):453-66. doi: 10.3109/1061186X.2012.685474. Epub 2012 May 4.