Towards vaccine optimisation

Lussow, A R; Aguado, M. Teresa; Giudice, Giuseppe Del; Lambert, Paul‐Henri

doi:10.1016/0165-2478(90)90124-9

Cited by 21 publications

(5 citation statements)

References 35 publications

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“…Because both lipopeptide 14 and 17 are self-adjuvanting, they eliminate the use of any adjuvant, which is one of the major obstacles facing the development of many subunit peptide-based vaccines. Furthermore, these analogues do not include a traditional carrier, like DT, and therefore may not suffer from problems including the administration of many unnecessary carrier associated epitopes and epitope suppression due to the existence of antibodies against the carrier . Lipopeptide 14 also offers many advantages over LCP system 17 , including ease of synthesis, as lipopeptide 14 does not contain a MAP system, and because it contains only one copy of each peptide antigen, it would be less expensive to manufacture.…”

Section: Resultsmentioning

confidence: 99%

Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

et al. 2007

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The development of 16 self-adjuvanting group A streptococcal vaccine candidates, composed of (i) a universal helper T-cell epitope (P25), (ii) a target GAS B-cell epitope (J14), and (iii) a lipid moiety, is described. Systemic J14-specific IgG antibodies were detected following subcutaneous immunization of BALB/c (H-2 (d)) mice with each construct without the need for an additional adjuvant. The effect of changing the order of P25, J14, and lipid moiety attachment or incorporation of P25 and J14 into a lipid-core peptide system on antibody titers was assessed. The point of lipid moiety attachment had the greatest influence on systemic J14-specific IgG antibody titers. Overall, the best vaccines featured a C-terminal lipid moiety, conjugated through a lysine residue to P25 at the N-terminus, and J14 on the lysine side chain.

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Section: Resultsmentioning

confidence: 99%

Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

et al. 2007

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“…With the ultimate aim of increasing the immunogenicity of synthetic and recombinant preparations, several attempts have been made towards the development of new safe and strong adjuvants acceptable for human use [3]. Along the same lines, in the development of polysaccharide vaccines against bacterial diseases much work is being devoted in the preparation and evaluation of polysaccharides conjugated to protein carriers, with the aim of increasing the protective immune response to the polysaccharide moiety in 5 18-month-old children [4].…”

Section: [I 10205]mentioning

confidence: 99%

Mycobacterial heat‐shock proteins as carrier molecules. II: The use of the 70‐kDa mycobacterial heat‐shock protein as carrier for conjugated vaccinescan circumvent the need for adjuvants and Bacillus Calmette Guérin priming)

et al. 1992

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In a recent work, we have shown that mycobacterial heat-shock proteins (hsp) of 65-kDa (GroEL-type) and 70-kDa (DnaK-type) acted as carrier molecules in mice, previously primed with Mycobacterium tuberculosis var. bovis (bacillus Calmette-Guérin, BCG), for the induction of high and long-lasting titers of IgG against the repetitive malaria synthetic peptide (NANP)40. Anti-peptide antibodies were induced when the malaria peptide, conjugated to the mycobacterial hsp, was given in the absence of any adjuvants (Lussow et al., Eur. J. Immunol. 1991. 87:2960). In this report, we show that mice immunized with peptides or oligosaccharides conjugated to the 70-kDa hsp produced high titers of IgG antibodies in the absence of any previous priming with BCG. The anti-peptide antibody response persisted for at least 1 year. This adjuvant-free carrier effect of the 70-kDa hsp was T cell dependent, since no anti-peptide nor anti-70-kDa IgG antibodies were induced in athymic nu/nu mice. Previous immunization of mice with the 65-kDa or 70-kDa hsp did not have any negative effect on the induction of anti-peptide IgG antibodies after immunization with hsp-peptide conjugates in the absence of adjuvants. Furthermore, preimmunization with the 65-kDa hsp could substitute for BCG in providing an effective priming for the induction of anti-(NANP) antibodies. Finally, both the 65-kDa and 70-kDa hsp acted as carrier molecules for the induction of IgG antibodies to group C meningococcal oligosaccharides, in the absence of adjuvants. These findings strongly suggest that the use of hsp as carriers in conjugated constructs for the induction of anti-peptide and anti-oligosaccharide antibodies could be of value in the design of new vaccines for eventual use in humans.

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“…consisting of selected native, recombinant or synthetic cpilopes from microorganisms, is their limited immunogenicity, due to their physicochcmical structure, their inability to encounter (he correct MHC restriction clement for T cell recognition, or the need for strong adjuvants to be delivered along with them [1,2]. These problems are usually solved by conjugating the target epitopes (peptides or oligosaccharides) with carrier proteins which provide a source ofT cell epitopes recognized by a wide proportion of the vaccinated population.…”

Section: Introductionmentioning

confidence: 99%

Specificity of antibodies induced after immunization of mice with the mycobacterial heat shock protein of 65 kD

Barrios

Tougne

Polla

et al. 1994

Clinical and Experimental Immunology

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SUMMARYWe have previously shown in mice and monkeys that mycobacterial heat shock proteins (hsp) of 65 and 70 kD exerl a strong in vivo helper effect when conjugated to synthetic peptides or bacterial oligosaccharides and given in the absence of any adjuvants. Considering the degree of homology existing in the phylogeny aniotig hsp belonging to the same family, we studied whether antibodies induced in mice with this protocol of immunization with the mycobacterial 65-kD hsp (hsp65) would cross-react, and to what extent, with hsp homologues from other origins, notably with the E.schcrichia coli GroEL protein and with the human homologue (hsp60). The results obtained show that antibodies to the mycobaclcrial hsp65 cross-reacted with the E. coli GroEL protein, bolh in ELISA and Western biol experiments, but nol witb ihe human hsp60. In competitive ELISA experiments, the binding of these antibodies to solid-phase hsp65 was very effeclively inhibited by low concentrations of the mycobaelerial hsp65; however, for human hsp60. 100 times higher concenirations were required in order to obtain similar patlerns of inhibition-Finally, murine antibodies to the mycobaelerial hsp65 always failed to give positive results in Western blol experiments using extracts of murinc cells. Taken together, these data suggest thai, after immunization of mice with the mycobacteria! hsp65 conjugated to peptides or oligosaccharides in the absence of adjuvanis, anti-hsp65 antibodies are induced which cross-react well with hsp homologues from other prokaryotes (e.g. E. coli GroEL), but which weakly bind the human hsp homologue. These results may have implications for the potential use of microbial hsp molecules in the design of conjugated vaccine constructs.

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Towards vaccine optimisation

Cited by 21 publications

References 35 publications

Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

Mycobacterial heat‐shock proteins as carrier molecules. II: The use of the 70‐kDa mycobacterial heat‐shock protein as carrier for conjugated vaccinescan circumvent the need for adjuvants and Bacillus Calmette Guérin priming)

Specificity of antibodies induced after immunization of mice with the mycobacterial heat shock protein of 65 kD

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