Article
The pan HLA DR-binding epitope improves adjuvant-assisted immunization with a recombinant protein containing a malaria vaccine candidate.
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862, 6th Floor, São Paulo 04023-062, SP, Brazil.
Immunology Letters (impact factor:
2.53).
05/2004;
92(3):259-68.
DOI:10.1016/j.imlet.2004.01.006
pp.259-68
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: Role of interferon-γ during CpG oligodeoxynucleotide-adjuvanted immunization with recombinant proteins
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ABSTRACT: Cited By (since 1996): 4, Export Date: 2 May 2012, Source: ScopusVaccine. 25(32):6007-6017. -
Article: Role of interferon-gamma during CpG oligodeoxynucleotide-adjuvanted immunization with recombinant proteins.
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ABSTRACT: Synthetic oligonucleotides (ODNs) containing immunostimulatory CpG motifs (CpG) are a new class of adjuvants suitable for the development of recombinant vaccines. Here we describe that endogenous interferon (IFN) was critical for the adjuvant activity of CpG ODN as genetically deficient mice developed significantly lower IgG antibody titers following immunization with recombinant proteins. In contrast, the absence of endogenous IL-12/IL-23 or IL-4 had little impact on the magnitude of the antibody response but instead caused a dramatic change in the pattern of IgG isotypes. The dependence on IFN-gamma was specific for CpG ODN and it was not observed with other adjuvants tested. IFN-gamma was produced by NK, dendritic cells, CD4+ and CD8+ T cells stimulated in vitro with CpG ODN. Adoptive transfer experiments confirmed that CD4+ or CD8+ T cells were in fact relevant sources of IFN-gamma in vivo. Following CpG ODN injection, splenic dendritic cells from IFN-gamma deficient mice did not up-regulate CD86 or CD40 expression, suggesting a role for these molecules. The importance of CD28 (CD86 ligand) was confirmed using CD28 deficient mice which presented severely impaired immune responses following CpG ODN-assisted immunization.Vaccine 09/2007; 25(32):6007-17. · 3.77 Impact Factor -
Article: Immunogenicity of self-associated aggregates and chemically cross-linked conjugates of the 42 kDa Plasmodium falciparum merozoite surface protein-1.
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ABSTRACT: Self-associated protein aggregates or cross-linked protein conjugates are, in general, more immunogenic than oligomeric or monomeric forms. In particular, the immunogenicity in mice of a recombinant malaria transmission blocking vaccine candidate, the ookinete specific Plasmodium falciparum 25 kDa protein (Pfs25), was increased more than 1000-fold when evaluated as a chemical cross-linked protein-protein conjugate as compared to a formulated monomer. Whether alternative approaches using protein complexes improve the immunogenicity of other recombinant malaria vaccine candidates is worth assessing. In this work, the immunogenicity of the recombinant 42 kDa processed form of the P. falciparum merozoite surface protein 1 (MSP1(42)) was evaluated as a self-associated, non-covalent aggregate and as a chemical cross-linked protein-protein conjugate to ExoProtein A, which is a recombinant detoxified form of Pseudomonas aeruginosa exotoxin A. MSP1(42) conjugates were prepared and characterized biochemically and biophysically to determine their molar mass in solution and stoichiometry, when relevant. The immunogenicity of the MSP1(42) self-associated aggregates, cross-linked chemical conjugates and monomers were compared in BALB/c mice after adsorption to aluminum hydroxide adjuvant, and in one instance in association with the TLR9 agonist CPG7909 with an aluminum hydroxide formulation. Antibody titers were assessed by ELISA. Unlike observations made for Pfs25, no significant enhancement in MSP1(42) specific antibody titers was observed for any conjugate as compared to the formulated monomer or dimer, except for the addition of the TLR9 agonist CPG7909. Clearly, enhancing the immunogenicity of a recombinant protein vaccine candidate by the formation of protein complexes must be established on an empirical basis.PLoS ONE 01/2012; 7(6):e36996. · 4.09 Impact Factor
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Keywords
19kDa C-terminal region
antibody immune response
antibody titers induced
BALB/c mice
C57BL/6 mice immunized
complete/incomplete Freund's adjuvant
distinct adjuvant formulations
IgG subclasses
malarial recombinant antigen
merozoite surface protein 1
new vaccine formulations
pan HLA DR-binding epitope
Plasmodium vivax vaccine candidate
rational design
recombinant malarial protein
recombinant protein His(6)MSP1(19)
recombinant protein His(6)MSP1(19)-PADRE
simple carrier epitope suitable
strong antibody responses
T cells specific
