Lipopeptides immunogenicity

Seth A, Yasutomi Y, Jacoby H, Callery JC, Kaminsky SM, Koff WC, Nixon DF, Letvin NL (2000) Evaluation of a lipopeptide immunogen as a therapeutic in HIV type 1-seropositive individuals. AIDS Res Hum Retroviruses 16(4) 337-343 Shahin RD, Amsbaugh DF, Leef MF (1992) Mucosal immunization with filamentous hemagglutinin protects against Bordetella pertussis respiratory infection. Infect Immun 60(4) 1482-1488... 

Bessler WG, et al. Bacterial lipopeptides constitute efficient novel immunogens and adjuvants in parenteral and oral immunization. Behring Inst Mitt 1997 98 390. 

There are many techniques that can be employed to assess the immuno-genicity of a vaccine candidate, and laboratories interested in pursuing this objective should also explore other assays suited to their purposes. In this model, vaccine immunogenicity is measured by determining levels of anti-LHRH antibodies induced in mice immunized with lipopeptide or a nonlipi-dated peptide control. It is important to correlate vaccine immunogenicity with biological function, and we measure the reproductively capability of vaccinated female mice as an indication of vaccine efficacy. Techniques that determine testosterone and oestrogen levels are also useful. 

Fig. 2. Immunogenicity of synthesized lipopeptide and nonlipidated peptide. Groups of BALB/c mice (6-8 wk old) were inoculated subcutaneously with 20 nmol of peptide immunogens in both primary and secondary inoculations. All lipopeptides were administered in saline, and the nonlipidated peptide was administered in either CFA or saline. Sera were obtained from blood taken 4 wk following the primary (open circles) inoculation and 2 wk following the secondary (closed circles) inoculation. Antibody levels were determined by ELISA. Individual antibody titers are presented with the mean value represented by the horizontal bar.

Zeng, W., Ghosh, S., Lau, Y.F., Brown, L.E., and Jackson, D.C. (2002) Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontra-ceptive vaccines. J. Immunol. 169(9), 4905 1912. 

Antigens conjugated to or co-administered with lipopeptides have been demonstrated in some cases to be immunogenic when administered via nasal (Zeng et al. 2000 Zeng et al. 2002 Batzloff et al. 2006) or oral routes (Nardelli et al. 1994) and are capable of eliciting both cell-mediated and humoral immune responses. Recent studies have investigated the use of... 

BenMohamed L, Thomas A, Bossus M, Brahimi K, Wubben J, Gras-Masse H, Druilhe P (2000) High immunogenicity in chimpanzees of peptides and lipopeptides derived from four new Plasmodium falciparum pre-erythrocytic molecules. Vaccine 18(25) 2843-2855... 

Mittenbuhler K, Baier W, van der Esche U, Heinevetter L, Wiesmuller K-H, Jung G, Weckesser J, Bessler WG, Hoffmann P (1997) Lipopeptides as efficient novel immunogens and adjuvants in parenteral and oral immunization. Curr Top Pept Prot Res 2 125-135... 

Metzger J, Wiesmuller K-H, Schaude R, Bessler WG, Jung G (1991) Syntlresis of novel immunologically active tiipalmitoyl-S-glycerylcysteinyl lipopeptides as useful intermediates for immunogen prepai ations. Int J Pept Protein Res 37 46-57. 

In these constructs, the amino terminus was acetylated and the carbojqr terminus liberated for further modification. Such derivatization included coupling of 33/34 to a synthetic lipopeptide, tripalmitoyl-S-glycerylcysteinylserine (PamsCysSer, 35) as immunological activator to afford fully synthetic derivatives 36 and 37. Alternatively, after global deprotection of 38, conjugation of 39 to an immunogenic carrier protein such as BSA or KLH produced the corresponding functional vaccines (Scheme 8). ... 

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