Novel adjuvant based on a proteoliposome‐derived cochleate structure containing native lipopolysaccharide as a pathogen‐associated molecular pattern

Immunology and Cell Biology - Tập 82 Số 6 - Trang 603-610 - 2004
Oliver Pérez1, Gustavo Bracho1, Miriam Lastre1, Néstor Mora1, Judith del Campo1, Danay Gil1, Caridad Zayas1, Reinaldo Acevedo1, Domingo González1, J. Alejandro López2, Carlos Taboada1, Rosa L. Solís1
1Finlay Institute, Havana, Cuba
2Mater Medical Research Institute, Brisbane, Australia

Tóm tắt

Proteoliposomes (PL) from Neisseria meningitidis B have been widely used as a core antigen for antimeningococcal vaccination. PL contain major outer membrane proteins, LPS and phospholipids, and they induce a strong Th1 immune response, but they have low stability in solution. Attending to the need for new vaccine adjuvants, we developed a highly stable cochleate structure (CS) from PL using a technology that allows easy incorporation of new antigens. We explored the ability of PLCS to activate the immune system and its possible application as an adjuvant for parenteral and mucosal routes. Our results showed that PLCS were able to upregulate the expression of MHC class II and costimulatory molecules on human dendritic cells, as well as being able to stimulate the production of soluble mediators of a Th1 response, such as IL‐12 and nitric oxide. High levels of anti‐PL IgG were detected in serum after i.m. or mucosal (oral and nasal) administration, but also anti‐PL secretory IgA was produced in saliva following nasal delivery. The immune response polarization to a Th1 pattern was confirmed by the induction of IgG2a antibodies, positive delayed type hypersensitivity reactions, and IFN‐γ production by splenocytes from immunized mice. The adjuvant potential was explored using PLCS containing ovalbumin (Ova). PLCS‐Ova was able to elicit a substantial increase in anti‐Ova IgG compared with Ova alone. In addition, a significant reduction in lesion size was observed in mice immunized with Leishmania major antigens in PLCS after challenge with virulent protozoa, suggesting at least partial modulation of the Th2 environment induced by this parasite. In conclusion, our results support the use of PLCS as a potent Th1 adjuvant for parenteral and mucosal vaccines.

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Tài liệu tham khảo

10.1016/S0952-7915(02)00365-5

10.1136/ard.61.suppl_2.ii25

PérezO BrachoG LastreMet al.Método de obtención de estructuras cocleares. Composiciones vacunales y adyuvantes basados en estructuras cocleares y sus intermediarios.2002. Patent application Cu 2002–0292.

O'Hagan D, 2003, Recent advances in the discovery and delivery of vaccine adjuvants, Nature Rev., 2, 727

Harandi AM, 2003, Recent developments in mucosal immunomodulatory adjuvants, Current Opinion Invest Drugs, 4, 156

10.1016/S1074-7613(01)00136-4

10.1016/S0167-4889(01)00182-3

Sierra VG, 1991, Vaccine against group B Neisseria meningitides: protection trial and mass vaccination results in Cuba, NIPH Ann., 195

10.1128/IAI.69.7.4502-4508.2001

10.1128/IAI.69.11.6912-6922.2001

Papahadjopoulos D, 1975, Cochleate lipid cylinders: Formation of unilamellar lipid vesicles, Biochim. Biophys. Acta, 394, 438

CampaC SierraVG GutiérrezMMet al.Method of producing Neisseria meningitidis B vaccine and vaccine produced by method. United States Patent1997. Patent number 5 597 572.

10.1046/j.1365-3024.1999.00224.x

10.1128/IAI.60.9.3725-3730.1992

10.1016/S0167-5699(99)01547-9

10.1016/S0165-2427(02)00042-9

10.1002/(SICI)1521-4141(199908)29:08<2498::AID-IMMU2498>3.0.CO;2-M

10.1078/1438-4221-00241

10.1080/000163501750541174

10.1038/nri933

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Thông tin xuất bản

Immunology and Cell Biology

Tập 82 Số 6

603-610

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